Efficacy and Safety of Atacicept in Systemic Lupus Erythematosus (ADDRESS II)

A Phase IIb, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multidose, 24-Week Study to Evaluate the Efficacy and Safety of Atacicept in Subjects With Systemic Lupus Erythematosus (SLE)

This is a multi-center, double-blind, randomized, Phase 2b trial to evaluate the efficacy of atacicept in subjects with systemic lupus erythematosus (SLE).

Study Overview

• Status: Completed
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Drug: Atacicept 75 milligram (mg); Drug: Atacicept 150 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 306
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina
    • Atencion Integral en Reumatologia (AIR)
  • Ciudad Autonoma Buenos Aires, Argentina
    • Hospital Italiano
  • Ciudad Autonoma Buenos Aires, Argentina
    • Organizacion Medica de Investigacion (OMI)
  • Ciudad Autonoma Buenos aires, Argentina
    • APRILLUS
  • Mar De Plata, Argentina
    • Policlìnica Red Omip S.A - Ensayos Clinicos GC
  • Pergamino, Argentina
    • Centro de Investigacion Pergamino SA
  • Salta, Argentina
    • Cordis S.A.
  • San Juan, Argentina
    • Centro Polivalente de Asistencia e Inv. Clinica CER
  • San Miguel de Tucuman, Argentina
    • Centro Medico Privado de Reumatologia
  • San Miguel de Tucuman, Argentina
    • Investigaciones Clínicas Tucumán
  • San Miguel de Tucumán, Argentina
    • Centro Integral de Reumatologia
• Brazil
  • Porto Alegre, Brazil
    • CPD - Centro de Pesquisas em Diabetes
  • Salvador, Brazil
    • CLION - Clínica de Oncologia da Bahia
  • Santa Catarina, Brazil
    • Clínica de Neoplasias Litoral Ltda.
  • São José do Rio Preto, Brazil
    • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
• Bulgaria
  • Plovdiv, Bulgaria
    • MHAT "Eurohospital" - Plovdiv, OOD
  • Ruse, Bulgaria
    • Medical Center "Teodora", EOOD
  • Sofia, Bulgaria
    • UMHAT "Sv. Ivan Rilski", EAD
  • Sofia, Bulgaria
    • DCC "Sveta Anna", EOOD
  • Stara Zagora, Bulgaria
    • Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
  • Targovishte, Bulgaria
    • MHAT-Targovishte, AD
• Chile
  • Santiago, Chile
    • Biomedica
  • Santiago, Chile
    • Centro de Estudios Reumatologicos
  • Santiago, Chile
    • Centro Medico Prosalud
  • Santiago, Chile
    • SOMEAL
  • Vina del Mar, Chile
    • CINVEC - Centro de Investigacion Clinica V Region
• Czechia
  • Plzen, Czechia
    • A-Shine, s.r.o.
  • Praha 2, Czechia
    • Vseobecna fakultni nemocnice v Praze
  • Praha 2, Czechia
    • Revmatologicky Ustav
  • Uherske Hradiste, Czechia
    • Medical Plus S.R.O.
• Germany
  • Bad Nauheim, Germany
    • Kerckhoff-Klinik gGmbH
  • Berlin, Germany
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
  • Frankfurt, Germany
    • Klinikum der Johann Wolfgang Goethe-Universitaet
  • Freiburg, Germany
    • Universitaetsklinikum Freiburg
  • Herne, Germany
    • Rheumazentrum Ruhrgebiet
  • Kiel, Germany
    • Universitaetsklinikum Schleswig-Holstein - Campus Kiel
  • Mainz, Germany
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
• Italy
  • Bari, Italy
    • Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari
  • Catania, Italy
    • Presidio Ospedaliero Vittorio Emanuele
  • Firenze, Italy
    • Azienda Ospedaliera Universitaria Careggi
  • Genova, Italy
    • Azienda Ospedaliero Universitaria San Martino
  • Milano, Italy
    • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo
• Japan
  • Chuo-ku, Japan
    • St. Luke's International Hospital
  • Fukuoka-shi, Japan
    • NHO Kyushu Medical Center
  • Meguro-ku, Japan
    • Toho University Ohashi Medical Center
  • Okayama-shi, Japan
    • Okayama University Hospital
  • Sagamihara-shi, Japan
    • Kitasato University Hospital
  • Sapporo-shi, Japan
    • Hokkaido University Hospital
  • Sapporo-shi, Japan
    • Sapporo City General Hospital
  • Sasebo-shi, Japan
    • Hakujujikai Sasebochuo Hospital
  • Sendai-shi, Japan
    • Tohoku University Hospital
  • Shimotsuke-shi, Japan
    • Jichi Medical University Hospital
  • Shinjuku, Japan
    • National Center for Global Health and Medicine Hospital
  • Tomigusuku-shi, Japan
    • Yuaikai Tomishiro Chuo Hospital
  • Tsukuba-shi, Japan
    • Tsukuba University Hospital
• Korea, Republic of
  • Incheon, Korea, Republic of
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of
    • Kyung Hee University Hospital
  • Suwon-si, Korea, Republic of
    • Ajou University Hospital
• Mexico
  • Chihuahua, Mexico
    • Investigacion y Biomedicina de Chihuahua, S.C.
  • Guadalajara, Mexico
    • Icle S.C.
  • Guadalajara, Mexico
    • Unidad de Investigacion en Enfermedades Cronico Degenerativas SC
  • Leon, Mexico
    • Investigacion Clinica de Leon S.C.
  • Leon, Mexico
    • Morales Vargas Centro de Investigacion, S.C.
  • Merida, Mexico
    • Centro de Estudios Clinicos Especializados
  • Monterrey, Mexico
    • Accelerium S. de R.L. de C.V.
  • Monterrey, Mexico
    • Alivia Clinica de Alta Especialidad S.A. de C.V.
  • Morelia, Mexico
    • Clínica de Enfermedades Crónicas y de Procedimientos Especiales, S.C.
  • Saltillo, Mexico
    • Hospital Universitario de Saltillo "Dr. Gonzalo Valdés Valdés"
• Peru
  • Lima, Peru
    • Clínica El Golf
  • Lima, Peru
    • Clinica Medica Cayetano Heredia
  • Lima, Peru
    • Clinica Vesalio
  • Lima, Peru
    • HMA - Hospital Maria Auxiliadora
• Philippines
  • Angeles City, Philippines
    • Angeles University Foundation Medical Center
  • Batangas, Philippines
    • Mary Mediatrix Medical Center
  • Davao City, Philippines
    • Davao Doctors Hospital
  • Iloilo City, Philippines
    • Iloilo Doctors Hospital
  • Quezon City, Philippines
    • St. Luke's Medical Center
• Poland
  • Bydgoszcz, Poland
    • Szpital Uniwersytecki nr 2 im.dr J. Biziela
  • Torun, Poland
    • Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z
  • Warsaw, Poland
    • Rheuma Medicus Zaklad Opieki Zdrowotnej
  • Warszawa, Poland
    • Wojskowy Instytut Medyczny
• Russian Federation
  • Barnaul, Russian Federation
    • SBEI HPE Altai State Medical University of MoH and SD
  • Kemerovo, Russian Federation
    • SBHI of Kem. "Regional Clinical Hospital for War Veterans"
  • Moscow, Russian Federation
    • First Moscow State Medical University n.a. I.M. Sechenov
  • Omsk, Russian Federation
    • Municipal City Hospital #2
  • Petrozavodsk, Russian Federation
    • Republican Hospital n.a. V.A. Baranov
  • Saratov, Russian Federation
    • City Clinical Hospital #12
  • Saratov, Russian Federation
    • Regional Clinical Hospital
  • St. Petersburg, Russian Federation
    • Clinical Rheumatology hospital #25
  • St. Petersburg, Russian Federation
    • Out - patient Clinic # 107
  • Vladimir, Russian Federation
    • Regional Clinical Hospital
  • Yaroslavl, Russian Federation
    • Yaroslavl State Medical University
• South Africa
  • Cape Town, South Africa
    • Dr CE Spargo and Dr RB Bhorat
  • Durban, South Africa
    • Naidoo, A
  • Stellenbosch, South Africa
    • Winelands Medical Research Centre
• Spain
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Sagunto, Spain
    • Hospital de Sagunto
  • Valladolid, Spain
    • Hospital Clínico Universitario de Valladolid
• United Kingdom
  • Bath, United Kingdom
    • Royal National Hospital for Rheumatic Diseases
  • Brighton, United Kingdom
    • Royal Sussex County Hospital
  • Coventry, United Kingdom
    • University Hospital Coventry
  • London, United Kingdom
    • Guy's Hospital
  • London, United Kingdom
    • University College London Hospitals
  • Wigan, United Kingdom
    • Wrightington Hospital
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group LLC
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham - (UAB)
  • California
    • Anaheim, California, United States, 92806
      • Southern California Permanente Medical Group
    • Los Angeles, California, United States, 90048
      • Wallace Rheumatic Study Center
    • San Leandro, California, United States, 94578
      • East Bay Rheumatology Medical Group, Inc.
  • Florida
    • Dunedin, Florida, United States, 34698
      • Clinical Research of West Florida - Corporate
    • Fort Lauderdale, Florida, United States, 33309
      • Center for Rheumatology, Immunology & Arthritis
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Goldpoint Clinical Research, LLC
  • Michigan
    • Grand Blanc, Michigan, United States, 48439
      • AA MRC LLC Ahmed Arif Medical Research Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North MS Medical Clinics, Inc.
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
  • New York
    • Manhasset, New York, United States, 11031
      • The Feinstein Institute for Medical Research
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Box Arthritis & Rheumatology of the Carolinas PLLC
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth System
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
    • Dayton, Ohio, United States, 45417
      • STAT Research, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Oklahoma City, Oklahoma, United States, 73104
      • OMRF
    • Oklahoma City, Oklahoma, United States, 73103
      • Arthritis & Rheumatology Center of Oklahoma
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
  • Texas
    • Galveston, Texas, United States, 77555
      • UTMB Pathology Clinical Services
    • Waco, Texas, United States, 76708
      • Arthritis & Osteoporosis Clinic
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Orthopedic Clinic, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible male and female subjects, aged 18 years or older
• Must have at least moderately active SLE, as defined as SLE Disease Activity Index-2000 (SLEDAI-2K) score greater than or equal to [>=] 6 at screening visit
• At least 4 of the 11 American college of rheumatology (ACR) classification criteria for SLE (diagnosed >= 6 months prior to the screening visit)
• Be seropositive for anti-nuclear antibodies (ANA) and/or anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Subjects have demyelinating disorder
• Severe central nervous system SLE
• Use of cyclophosphamide within 3 months of the screening visit
• Urine protein:creatinine ratio (UPCr) >= 2 milligram per milligram (mg/mg) per day
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo matched to atacicept will be administered as subcutaneous injection once weekly for 24 weeks.
Experimental: Atacicept 75 mg	Drug: Atacicept 75 milligram (mg); Atacicept 75 mg will be administered as subcutaneous injection once weekly for 24 weeks.
Experimental: Atacicept 150 mg	Drug: Atacicept 150 mg; Atacicept 150 mg will be administered as subcutaneous injection once weekly for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline	SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score.	Week 24
Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Day 1 as Baseline	SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects at Week 24 Whose Prednisone-Equivalent Corticosteroid (CS) Dose Reduced From Screening by >=25% and to a Dose of =<7.5mg/Day, and no British Isles Lupus Assessment Group (BILAG) A or 2B Flare in Disease Activity	BILAG A or 2B flare is defined by 1 new BILAG A organ domain score and/or 2 new BILAG B organ domain scores compared to the Screening Visit. The BILAG disease activity index evaluates systemic lupus erythematosus (SLE) activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone >20 mg daily or immunosuppressants); BILAG B: moderate disease activity requiring treatment with systemic low-dose oral glucocorticoids, intramuscular or intra-articular or soft tissue CS injection, topical CS or immunosuppressants, or symptomatic therapy such as antimalarials or NSAIDs. BILAG C: mild disease; BILAG D: system previously affected but now inactive and BILAG E: system never involved.	Week 24
Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24	The PGIC is self-rated scale that asks the subject to describe the change in activity limitations, symptoms, emotions, and overall Quality of life (QoL) related to the subject's painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Percentage of subjects in the PGIC categories of very much or much improved (1 or 2), minimally improved or no change or minimally worse (3 or 4 or 5) and much or very much worse (6 or 7) at Week 24 were presented.	Week 24
Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24	Change From screening visit to Week 24 of prednisolone-equivalent CS daily dose was presented.	Screening and Week 24
Time From Randomization to First SRI Response During Treatment Period	SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score. Time to first SRI response during treatment period was presented.	Baseline up to 24 Weeks
Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24	The BICLA response is defined as BILAG-2004 improvement (all screening visit BILAG A improving to B/C/D, all screening visit BILAG B to C/D, and <=1 new BILAG B and no new BILAG A); no deterioration in SLEDAI total score; PGA increase by <10% (defined as <0.3 point increase for the statistical analyses) and no nonpermitted medication/treatment.	Week 24
Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 48 weeks. TEAEs include both Serious TEAEs and non-serious TEAEs.	Baseline up to 24 weeks after last dose of study drug (assessed up to maximum of 48 weeks)
Change From Week 0 (Day 1) in SF-36 Components at Week 24	The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component summary scores. Total of 10 variables were analyzed (8 aspects, 2 component summary scores). The score for each of the 8 aspects and 2 component summary scores was scaled from 0 to 100, where 0 = lowest level of functioning and 100 = highest level of functioning.	Week 0 (Day 1) and Week 24

Collaborators and Investigators

• Sponsor: EMD Serono

Publications and helpful links

General Publications

• Morand EF, Isenberg DA, Wallace DJ, Kao AH, Vazquez-Mateo C, Chang P, Pudota K, Aranow C, Merrill JT. Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study. Rheumatology (Oxford). 2020 Oct 1;59(10):2930-2938. doi: 10.1093/rheumatology/keaa029.
• Merrill JT, Wallace DJ, Wax S, Kao A, Fraser PA, Chang P, Isenberg D; ADDRESS II Investigators. Efficacy and Safety of Atacicept in Patients With Systemic Lupus Erythematosus: Results of a Twenty-Four-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm, Phase IIb Study. Arthritis Rheumatol. 2018 Feb;70(2):266-276. doi: 10.1002/art.40360. Erratum In: Arthritis Rheumatol. 2018 Mar;70(3):467. Arthritis Rheumatol. 2021 Nov;73(11):2043.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: October 24, 2013
• First Submitted That Met QC Criteria: October 24, 2013
• First Posted (Estimate): October 30, 2013

Study Record Updates

• Last Update Posted (Actual): January 2, 2018
• Last Update Submitted That Met QC Criteria: December 4, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Placebo; Atacicept
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: 700461-023; 2013-002773-21 (EudraCT Number)