Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus

A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus With Inadequate Response to Standard of Care Therapy

The primary objective is to evaluate the efficacy and safety of efavaleukin alfa in subjects with active systemic lupus erythematosus.

Study Overview

• Status: Terminated
• Conditions: Active Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Placebo; Other: Standard of Care; Drug: Efavaleukin Alfa

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaet Graz
• Bulgaria
  • Plovdiv, Bulgaria, 40002
    • Diagnostic-Consultative Center Sveti Georgi EOOD
  • Sofia, Bulgaria, 1407
    • Medical Center Excelsior OOD
  • Sofia, Bulgaria, 1612
    • Medical Center Academy EOOD
  • Sofia, Bulgaria, 1612
    • University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
• Chile
  • Osorno, Chile, 5311092
    • Corporacion de Beneficiencia Osorno
  • Santiago, Chile, 7501126
    • Estudios Clinicos Limitada - Centro de Estudios Reumatologicos
  • Santiago, Chile, 8320000
    • CECIM
  • Valdivia, Chile, 5111847
    • Sociedad de Prestaciones Medicas Intermedica Limitada
  • Viña del Mar, Chile, 2520598
    • Oncocentro APYS
  • Santiago
    • Providencia, Santiago, Chile, 7500010
      • Investigacion y Terapias Reumatologicas Innovadoras LTDA - Interin LTDA
    • Providencia, Santiago, Chile, 7500587
      • Enroll Spa
    • Providencia, Santiago, Chile, 7510047
      • Sociedad de prestaciones Medicas y Paramedicas Goecke Gatica y Compania Limitada - Prosalud
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050034
      • Hospital Pablo Tobon Uribe
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080002
      • Centro Integral de Reumatología del Caribe Circaribe SAS
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110221
      • Centro de Investigacion en Reumatologia y Especialidades Medicas SAS
    • Bogota, Cundinamarca, Colombia, 110221
      • Solano y Terront Servicios Medicos Ltda - Uniendo
  • Tolima
    • Ibague, Tolima, Colombia, 730006
      • Mediservis del Tolima IPS SAS
  • Valle Del Cauca
    • Santiago de Cali, Valle Del Cauca, Colombia, 760035
      • Centro Medico Julian Coronel
• France
  • Montpellier cedex 05, France, 34295
    • Centre Hospitalier Universitaire de Montpellier Hopital Lapeyronie
  • Strasbourg, France, 67091
    • Centre Hospitalier Universitaire de Strasbourg - Nouvel Hopital Civil
  • Toulouse Cedex 9, France, 31059
    • Centre Hospitalier Universitaire de Toulouse - Hôpital Rangueil
  • Vandoeuvre Les Nancy Cedex, France, 54511
    • Centre Hospitalier Universitaire de Nancy - Hôpital de Brabois
• Greece
  • Athens, Greece, 11527
    • Laiko General Hospital
  • Athens, Greece, 11521
    • Athens Naval Hospital
  • Athens, Greece, 12462
    • Attiko Hospital
  • Heraklion, Greece, 71500
    • University Hospital of Heraklion
  • Patra, Greece, 26443
    • Olympion Hospital-General Clinic of Patras AE
  • Thessaloniki, Greece, 54636
    • Euromedica - Kyanous Stavros
  • Thessaloniki, Greece, 54642
    • Ippokrateio Hospital of Thessaloniki
• Hong Kong
  • New Territories, Hong Kong
    • Tuen Mun Hospital
• Italy
  • Firenze, Italy, 50139
    • Azienda Ospedaliera Universitaria Careggi
  • Napoli, Italy, 80131
    • Università degli studi della Campania Luigi Vanvitelli
  • Padova, Italy, 35128
    • Azienda Ospedaliera Di Padova
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 00161
    • Azienda Ospedaliera Policlinico Umberto I
  • Torino, Italy, 10128
    • Azienda Ospedaliera Ordine Mauriziano di Torino
  • Udine, Italy, 33100
    • Azienda Ospedaliero Universitaria Integrata Santa Maria della Misericordia
  • Verona, Italy, 37134
    • Centro Ricerche Cliniche
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
    • Nagoya-shi, Aichi, Japan, 457-8510
      • Japan Community Healthcare Organization Chukyo Hospital
  • Chiba
    • Chiba-shi, Chiba, Japan, 260-8712
      • National Hospital Organization Chibahigashi National Hospital
  • Fukuoka
    • Kitakyushu-shi, Fukuoka, Japan, 807-8556
      • Hospital of the University of Occupational and Environmental Health Japan
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 734-8551
      • Hiroshima University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
    • Sapporo-shi, Hokkaido, Japan, 060-8604
      • Sapporo City General Hospital
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 890-8520
      • Kagoshima University Hospital
    • Kagoshima-shi, Kagoshima, Japan, 890-0063
      • Eiraku Clinic
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 216-8511
      • St Marianna University Hospital
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 980-8574
      • National University Corporation Tohoku University Tohoku University Hospital
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 852-8501
      • Nagasaki University Hospital
  • Shizuoka
    • Hamamatsu-shi, Shizuoka, Japan, 430-8558
      • Seirei Hamamatsu General Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Chuo-ku, Tokyo, Japan, 104-8560
      • St Lukes International Hospital
    • Meguro-ku, Tokyo, Japan, 152-8902
      • National Hospital Organization Tokyo Medical Center
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital
    • Shinjuku-ku, Tokyo, Japan, 162-8655
      • Center Hospital of the National Center for Global Health and Medicine
• Korea, Republic of
  • Daegu, Korea, Republic of, 42472
    • Daegu Catholic Universtiy Medcial Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 04763
    • Hanyang University Seoul Hospital
  • Suwon-si, Gyeonggi-do, Korea, Republic of, 16499
    • Ajou University Hospital
• Mexico
  • Chihuahua, Mexico, 31203
    • Centro de Investigacion Integral Medivest SC
  • Cuautitlan Izcalli, Mexico, 54769
    • Phylasis Clínicas Research S. De R. L. De C. V.
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 06700
      • CITER SA de CV (Centro de Investigación y Tratamiento de las Enfermedades Reumáticas SA de CV)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Centro Integral en Reumatologia SA de CV
    • Guadalajara, Jalisco, Mexico, 44690
      • Centro de Estudios de Investigacion Basica y Clinica, Sc
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64718
      • Eukarya Pharmasite sc
• Poland
  • Bydgoszcz, Poland, 85-605
    • Centrum medyczne intercore sp zoo
  • Czestochowa, Poland, 42-200
    • Centrum Medyczne Pratia Częstochowa
  • Malbork, Poland, 82-200
    • Centrum Badan Klinicznych Wojciech Brzezicki
  • Nadarzyn, Poland, 05-830
    • NZOZ Lecznica Mak-Med sc
  • Poznan, Poland, 61-441
    • Gabinety Lekarskie Rivermed
  • Wroclaw, Poland, 52-210
    • Reumatop Grzegorz Rozumek, Karin Pistorius
• Russian Federation
  • Kazan, Russian Federation, 420097
    • Limited liability company Scientific Research Medical Complex Your Health
  • Moscow, Russian Federation, 115522
    • FSBSI SRI of Rheumatology na V A Nasonova
  • Moscow, Russian Federation, 119435
    • I M Sechenov First Medical University of the MoH of RF
  • Saint Petersburg, Russian Federation, 196066
    • LLC Medical Sanitary Unit №157
  • Saint-Petersburg, Russian Federation, 190068
    • Saint-Petersburg State Budget Healthcare Institution Clinical Rheumatology Hospital 25
  • Yaroslavl, Russian Federation, 150003
    • Center for medical consultations and research - practice
• Spain
  • Andalucía
    • Cordoba, Andalucía, Spain, 14004
      • Hospital Universitario Reina Sofia
    • Sevilla, Andalucía, Spain, 41010
      • Hospital Infanta Luisa
  • Canarias
    • Santa Cruz de Tenerife, Canarias, Spain, 38001
      • Hospital Universitario Hospiten Rambla
  • Cataluña
    • Barcelona, Cataluña, Spain, 08041
      • Hospital De La Santa Creu I Sant Pau
    • Sabadell, Cataluña, Spain, 08208
      • Corporacio Sanitaria Parc Tauli
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Hospital Universitari i Politecnic La Fe
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Hospital Clinico Universitario de Santiago
  • País Vasco
    • Vitoria, País Vasco, Spain, 01009
      • Hospital Universitario Araba
• Switzerland
  • Basel, Switzerland, 4031
    • Universitaetsspital Basel
  • Sankt Gallen, Switzerland, 9007
    • Kantonsspital St Gallen
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 40201
    • Chung Shan Medical University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Turkey
  • Adana, Turkey, 01790
    • Cukurova Universitesi Balcali Hastanesi Saglik Uygulama ve Arastirma Merkezi
  • Ankara, Turkey, 06100
    • Hacettepe Universitesi Tip Fakultesi
  • Antalya, Turkey, 07070
    • Akdeniz Universitesi Tip Fakultesi
  • Istanbul, Turkey, 34093
    • Istanbul Universitesi Istanbul Tip Fakultesi
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham,Arthritis Clinical Intervention Program
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Arizona Arthritis and Rheumatology Associates PC
    • Glendale, Arizona, United States, 85306
      • Arizona Arthritis and Rheumatology Associates PC
    • Tucson, Arizona, United States, 85704
      • Arizona Arthritis and Rheumatology Associates PC
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care
    • Los Angeles, California, United States, 90024
      • University of California Los Angeles
    • Orange, California, United States, 92868
      • University of California Irvine
    • Tustin, California, United States, 92780
      • Robin K Dore MD Inc
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis and Rheumatic Disease Specialties
    • Aventura, Florida, United States, 33180
      • LIFE Clinical Trials
    • Fort Lauderdale, Florida, United States, 33309
      • Centre for Rheumatology Immunology and Arthritis
    • Hollywood, Florida, United States, 33024
      • GNP Research
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology And Immunology Specialists
    • Saint Petersburg, Florida, United States, 33710
      • Suncoast Medical Clinic
    • Tampa, Florida, United States, 33614
      • BayCare Medical Group Inc
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Schaumburg, Illinois, United States, 60195
      • Greater Chicago Specialty Physicians
    • Skokie, Illinois, United States, 60076
      • Clinic of Robert Hozman, MD - Clinical Investigational Specialists, Inc
  • Kentucky
    • Hopkinsville, Kentucky, United States, 42240
      • Western Kentucky Rheumatology PLLC
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Accurate Clinical Research
  • Michigan
    • Grand Blanc, Michigan, United States, 48439
      • Michigan Rheumatology Group, PC - Grand Blanc Office
    • Lansing, Michigan, United States, 48910
      • Arthritis and Rheumatology of Michigan
  • New York
    • Bronx, New York, United States, 10461
      • Institute for Clinical and Translation Research at Einstein and Montefiore Clinical Research Center
    • Brooklyn, New York, United States, 11201
      • New York University Langone Ambulatory Care Brooklyn Heights
    • Manhasset, New York, United States, 11030
      • Feinstein Institute for Medical Research
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill Thurston Arthritis Research Center
    • Charlotte, North Carolina, United States, 28204
      • Joint and Muscle Research Institute
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research PLLC
    • Charlotte, North Carolina, United States, 28210
      • Javara
    • Charlotte, North Carolina, United States, 28211
      • Atrium Health Rheumatology
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
    • Oklahoma City, Oklahoma, United States, 73102
      • Arthritis and Rheumatology Center of Oklahoma PLLC
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center Lupus Center of Excellence
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Columbia Arthritis Center, PA
    • Greenville, South Carolina, United States, 29601
      • Piedmont Arthritis Clinic
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute, llc
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
    • Memphis, Tennessee, United States, 38119
      • Ramesh C Gupta MD
  • Texas
    • Allen, Texas, United States, 75013
      • Arthritis and Rheumatology Institute
    • Colleyville, Texas, United States, 76034
      • Precision Comprehensive Clinical Research Solutions
    • El Paso, Texas, United States, 79902
      • Texas Arthritis Center PA
    • Houston, Texas, United States, 77043
      • Biopharma Informatic, LLC
    • Houston, Texas, United States, 77089
      • Laila A Hassan, MD, PA
    • Houston, Texas, United States, 77084
      • Accurate Clinical Management
    • Plano, Texas, United States, 75024
      • Trinity Universal Research Associates, LLC
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio Medical Arts Research Clinic Marc
    • Waco, Texas, United States, 76710
      • Arthritis And Osteoporosis Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Participant is aged between 18 and 75.
• Fulfills classification criteria for systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE with antinuclear antibody ≥ 1:80 by immunofluorescence on Hep-2 cells being present at screening.
• Hybrid SLEDAI score ≥ 6 points with a "Clinical" hSLEDAI score ≥ 4 points. The "Clinical" hSLEDAI is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results, including urine or immunologic parameters.
• British-Isles Lupus Assessment Group (BILAG) index score (BILAG 2004) of ≥ 1 A item or ≥ 2 B items.
• Must be taking ≥ 1 of the following SLE treatments (or regional equivalent): hydroxychloroquine, chloroquine, quinacrine, mycophenolate mofetil, azathioprine, methotrexate, dapsone, or oral calcineurin inhibitors, or OCS. A participant may enter the study on OCS alone (prednisone ≥ 10 mg/day or equivalent) only if the participant has previously documented trial of anti-malarial or immunosuppressant treatment for SLE. Participants must be on a stable dose for ≥ 8 weeks prior to screening for all antimalarials and immunosuppressants, with the exception of OCS doses which must be stable for ≥ 2 weeks prior to screening.
• For participants taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS equivalent, and the dose must be stable at baseline visit and for ≥ 2 weeks prior to screening visit.
• Stability of SLE treatments: OCS and other immunosuppressants/immunomodulator agents and doses must be stable since screening visit.
• Disease activity: active disease as indicated by clinical hSLEDAI score ≥ 4 must be observed (clinical hSLEDAI score is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results including urine and immunologic parameters).

Exclusion Criteria:

• Lupus nephritis if any of the following are present: urine protein creatinine ratio ≥ 2000 mg/g (or equivalent) at screening, OR requiring induction therapy currently or within 1 year prior to screening, OR histological evidence (if available) of diffuse proliferative glomerulonephritis within 12 weeks prior to screening.
• Active CNS lupus within 1 year prior to screening including, but not limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.
• Currently present or within 1 year prior to screening a diagnosis of any chronic inflammatory disease other than SLE (eg, rheumatoid arthritis) which would interfere with SLE disease assessment.
• History of any disease other than SLE that has required treatment with oral or parenteral corticosteroids for > 2 weeks within 4 months prior to screening.
• Active infection (including chronic or localized infections) for which anti-infectives are indicated currently or within 4 weeks prior to screening visit OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to screening visit.
• Active tuberculosis or latent tuberculosis with no documented past history of adequate treatment per local standard of care.
• Positive test for tuberculosis during creening defined as: either a positive or indeterminate QuantiFERON®-TB or T-spot test OR positive purified protein derivative (PPD) (≥5 mm of induration at 48 to 72 hours after test is placed).
• Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody (HBcAb). A history of hepatitis B vaccination without history of hepatitis B infection (ie, positive hepatitis B surface antibody (HBsAb), negative HBsAg and negative HBcAb) is allowed.
• Positive for hepatitis C antibody.
• Known history of HIV or positive HIV test at screening.

• Presence of 1 or more significant concurrent medical conditions, including but not limited to the following:

  • poorly controlled diabetes (hemoglobin A1C > 7) or hypertension
  • symptomatic heart failure (New York Heart Association class III or IV)
  • myocardial infarction or unstable angina pectoris within the past 12 months prior to screening
  • severe chronic pulmonary disease requiring oxygen therapy
  • multiple sclerosis or any other demyelinating disease
• Any history of malignancy with the following exceptions:
• resolved non-melanoma skin cancers > 5 years prior to screening
• resolved cervical carcinoma > 5 years prior to screening
• resolved breast ductal carcinoma in situ > 5 years of screening
• Currently receiving or had treatment with: cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent within 6 months prior to screening or sirolimus within 4 weeks prior screening.
• Currently receiving or had treatment with a Janus kinase (JAK) inhibitor within 3 months or less than 5 drug half-lives (whichever is longer) prior to screening.
• Currently receiving or had treatment with an immune checkpoint inhibitor (eg, programmed death 1 [PD-1] inhibitor, programmed death ligand 1 [PD-L1] inhibitor, cytotoxic T-lymphocyte associated protein 4 [CTLA-4] inhibitor).

Note: Abatacept is not considered a CTLA-4 inhibitor and is referred to below.

• Currently receiving or had treatment within 12 months prior to screening with T-cell depleting agents (eg, antithymocyte globulin, Campath).
• Currently receiving of had treatment with an interleukin 2 (IL-2) based therapy (eg, Proleukin).
• Current or previous treatment with a biologic agent with immunosuppressive/immunomodulatory activity as follows: rituximab within 6 months prior to screening; abatacept and belimumab within the past 3 months prior to screening; other biologics within < 5 drug half lives prior to screening.
• Participants who have received intraarticular, intralesional, or intramuscular corticosteroids within 2 weeks prior to screening or intravenous corticosteroids within 6 weeks prior to screening.
• Participants who have received live vaccines within 5 weeks prior to screening, or plan to receive live vaccines during the treatment period and up to 6 weeks after the end of treatment period in the study.
• Currently receiving treatment in another investigational device or drug study.
• Ending a treatment with an investigational drug or investigational device less than 3 months or 5 half-lives from the last dose of the investigational drug (whichever is longer) at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + Standard of Care	Drug: Placebo; Administered as a subcutaneous (SC) injection.; Other: Standard of Care; Standard of care procedures and therapies for managing active systemic lupus erythematosus will be carried out according to each investigator's standard procedures.
Experimental: Efavaleukin Alfa Dose Level One + Standard of Care	Other: Standard of Care; Standard of care procedures and therapies for managing active systemic lupus erythematosus will be carried out according to each investigator's standard procedures.; Drug: Efavaleukin Alfa; Administered as a subcutaneous (SC) injection.; Other Names: AMG 592
Experimental: Efavaleukin Alfa Dose Level Two + Standard of Care	Other: Standard of Care; Standard of care procedures and therapies for managing active systemic lupus erythematosus will be carried out according to each investigator's standard procedures.; Drug: Efavaleukin Alfa; Administered as a subcutaneous (SC) injection.; Other Names: AMG 592
Experimental: Efavaleukin Alfa Dose Level Three + Standard of Care	Other: Standard of Care; Standard of care procedures and therapies for managing active systemic lupus erythematosus will be carried out according to each investigator's standard procedures.; Drug: Efavaleukin Alfa; Administered as a subcutaneous (SC) injection.; Other Names: AMG 592

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response at Week 52	A participant achieved an SRI-4 response if all the following criteria were met: ≥ 4-point reduction from baseline in Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score (scale 0-105, with higher scores indicating more disease activity).; No new British-Isles Lupus Assessment Group (BILAG) A score and no > 1 new BILAG B organ domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present).; < 0.3-points deterioration from baseline in Physician Global Assessment (PGA) visual analogue (VAS) score (scale 0 to 3, with higher scores indicating more severe disease). Participants were considered non-responders for using more than protocol-permitted therapies.	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved a BILAG-based Composite Lupus Assessment (BICLA) Response at Week 52	A participant achieved a BICLA response if all the following criteria were met: At least 1 gradation of improvement in baseline BILAG domain scores in all body systems with moderate or severe disease activity at entry and no > 1 BILAG B domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present).; No worsening of the hSLEDAI score from baseline (scale 0-105, with higher scores indicating more disease activity).; < 0.3-points deterioration from baseline in PGA VAS (scale 0 to 3, with higher scores indicating more severe disease).; No initiation of non-protocol treatment.	Week 52
Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) Response at Week 52	A participant achieved an LLDAS response if all the following criteria were met: hSLEDAI ≤ 4 (scale 0-105, higher scores indicating more disease activity) with no activity in major organ systems (renal [proteinuria, hematuria, pyuria, urinary casts], central nervous system [seizure, psychosis, organic brain syndrome, cranial nerve disorder, cerebrovascular accident], cardiopulmonary [pericarditis, pleurisy], vasculitis and fever) & no hemolytic anemia or gastrointestinal activity in BILAG. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active) to E (never present).; No new lupus disease activity compared with previous assessment defined as no new descriptor scores in hSLEDAI.; A score of < 1 in PGA VAS score (scale 0 to 3, with higher scores indicating more severe disease).; Current prednisolone dose ≤ 7.5 mg daily.; No increase or initiation of immunosuppressive drugs.	Week 52
Number of Participants With a Reduction of Oral Corticosteroids (OCS) to ≤ 7.5 mg/Day by Week 44 and Sustained Through Week 52 in Participants With a Baseline OCS Dose ≥ 10 mg/Day	Participants taking OCS could begin tapering OCS after the Week 12 assessment up to the Week 44 assessment with initiation of tapering based upon clinical judgement of the treating physician. The tapering schedule was at the discretion of the investigator but should not have been tapered more than 20% of the prior dose per week. Tapering OCS before Week 12 was not encouraged but may have been allowed based upon investigator's judgement. Between weeks 44 and 52, the OCS dosing must again have remained stable.	Baseline to Week 52
Number of Participants Who Achieved a SRI-4 Response at Week 24	A participant achieved an SRI-4 response if all the following criteria were met: ≥ 4-point reduction from baseline in hSLEDAI score (scale 0-105, with higher scores indicating more disease activity).; No new BILAG A score and no > 1 new BILAG B organ domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present).; < 0.3-points deterioration from baseline in PGA VAS score (scale 0 to 3, with higher scores indicating more severe disease). Participants were considered non-responders for using more than protocol-permitted therapies.	Week 24
Number of Participants Who Achieved a BICLA Response at Week 24	A participant achieved a BICLA response if all the following criteria were met: At least 1 gradation of improvement in baseline BILAG domain scores in all body systems with moderate or severe disease activity at entry and no > 1 BILAG B domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present).; No worsening of the hSLEDAI score from baseline (scale 0-105, with higher scores indicating more disease activity).; < 0.3-points deterioration from baseline in PGA VAS (scale 0 to 3, with higher scores indicating more severe disease).; No initiation of non-protocol treatment.	Week 24
Number of Participants With a hSLEDAI Response at Week 24 and Week 52	The hSLEDAI is a global index that evaluates disease activity and includes both laboratory and clinical parameters. The score ranges from 0 to 105, with higher scores indicating more disease activity. A participant achieved a hSLEDAI response if there was a ≥ 4-point reduction in hSLEDAI from baseline.	Week 24 and Week 52
Number of Participants With an Improvement From Baseline in Tender and Swollen Joint Count ≥ 50% at Weeks 8, 12, 24, 36, and 52 in Participants With ≥ 6 Tender and Swollen Joints in Hands and Wrists	The swollen and tender join count assessments were performed at the site by an experienced independent and blinded joint evaluator. Joints in hands and wrists were scored for the simultaneous presence (1) or absence (0) of swelling and tenderness. Scores ranged from 0-28. A higher score indicates more severe disease.	Weeks 8, 12, 24, 36 and 52
Number of Participants With an Improvement From Baseline in Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score ≥ 50% at Week 8, 12, 24, 36, and 52 in Participants With a CLASI Activity Score ≥ 8 at Baseline	The CLASI consists of 2 scores, the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The total score ranges from 0-70, with higher scores indicating more severe disease.	Weeks 8, 12, 24, 36 and 52
Annualized Flare Rate Over 52 Weeks	A flare was defined as a BILAG score designation of "worse" or "new" resulting in a B score in ≥ 2 organs or an A score in ≥ 1 organ. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied by 365.25.	Up to 52 weeks
Change From Baseline in Fatigue Standardized Score Using the Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Instrument at Week 12, 24, 36 and 52	The PROMIS Fatigue SF 7a assesses the experience of fatigue as well as its impact on physical, mental and social activities. The score ranges from 7 to 35, with higher scores indicating more fatigue. A negative change from baseline indicates a reduction in fatigue. Efficacy data collected after the study termination decision date were censored and excluded from analyses for that particular visit.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Physical Component Score of the Medical Outcomes Short Form-36 Questionnaire Version 2 (SF-36V2) at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Mental Component Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Physical Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Social Role Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Physical Role Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Bodily Pain Domain Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Mental Health Domain Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Emotional Role Domain Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Vitality Domain Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the General Health Domain Score of the SF-36V2 at Week 12, 24, 36 and 52	The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems.; Limitations in usual role activities because of physical health problems.; Bodily pain.; General mental health (psychological distress and well-being).; Limitations in usual role activities because of emotional problems.; Vitality (energy and fatigue).; General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Physical Health Domain Score of the Lupus Quality of Life (LupusQoL) at Week 12, 24, 36 and 52	The LupusQoL is a systemic lupus erythematosus (SLE)-specific health-related QoL instrument and consists of 8 domains: Physical health.; Pain.; Planning.; Intimate relationships.; Burden to others.; Emotional health.; Body image.; Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Pain Domain Score of the LupusQoL at Week 12, 24, 36 and 52	The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: Physical health.; Pain.; Planning.; Intimate relationships.; Burden to others.; Emotional health.; Body image.; Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Planning Domain Score of the LupusQoL at Week 12, 24, 36 and 52	The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: Physical health.; Pain.; Planning.; Intimate relationships.; Burden to others.; Emotional health.; Body image.; Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Intimate Relationship Domain Score of the LupusQoL at Week 12, 24, 36 and 52	The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: Physical health.; Pain.; Planning.; Intimate relationships.; Burden to others.; Emotional health.; Body image.; Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Burden to Others Domain Score of the LupusQoL at Week 12, 24, 36 and 52	The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: Physical health.; Pain.; Planning.; Intimate relationships.; Burden to others.; Emotional health.; Body image.; Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Emotional Health Domain Score of the LupusQoL at Week 12, 24, 36 and 52	The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: Physical health.; Pain.; Planning.; Intimate relationships.; Burden to others.; Emotional health.; Body image.; Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Body Image Domain Score of the LupusQoL at Week 12, 24, 36 and 52	The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: Physical health.; Pain.; Planning.; Intimate relationships.; Burden to others.; Emotional health.; Body image.; Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Change From Baseline in the Fatigue Domain Score of the LupusQoL at Week 12, 24, 36 and 52	The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: Physical health.; Pain.; Planning.; Intimate relationships.; Burden to others.; Emotional health.; Body image.; Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.	Baseline to Week 12, 24, 36 and 52
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)	A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment and had emerged or worsened during treatment. A serious TEAE was defined as any untoward medical occurrence that, met at least 1 of the following criteria: Resulted in death (fatal).; Was immediately life-threatening.; Required in-patient hospitalization or prolongation of existing hospitalization.; Resulted in persistent or significant disability/incapacity.; Was a congenital anomaly/birth defect.; Was any other medically important serious event. Clinically significant changes from baseline in laboratory values and vital signs were also recorded as TEAEs.	Day 1 to Week 56
Serum Efavaleukin Alfa Concentrations by Timepoint	Serum efavaleukin alfa concentrations by timepoint after multiple dose subcutaneous administration of efavaleukin alfa to participants with active systemic lupus erythematosus. Lower limit of quantification= 0.100 ng/mL.	Day 1: 6-24 and 48-96 hrs, Day 29, Day 43: 6-24 and 48-96 hrs, Day 85, Day 169, Day 253, Day 309, and Day 365

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Actual): May 22, 2023
• Study Completion (Actual): May 22, 2023

Study Registration Dates

• First Submitted: December 18, 2020
• First Submitted That Met QC Criteria: December 18, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 28, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: 20200234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No