Study of VIB7734 for the Treatment of Moderate to Severely Active SLE (RECAST SLE)

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of VIB7734 for the Treatment of Moderate to Severely Active Systemic Lupus Erythematosus

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of VIB7734 for the Treatment of Moderate to Severely Active Systemic Lupus Erythematosus in approximately 195 participants. The study duration will be 48 weeks, with a safety follow-up through week 56.There will be 3 parallel arms - 2 active treatment and 1 placebo.

Study Overview

• Status: Completed
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Other: Placebo; Drug: VIB7734

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ABP
      • Consultorios Médicos Dr. Doreski
    • Estomba, Buenos Aires, Argentina, C1430EGF
      • Clinica Adventista Belgrano
    • La Plata, Buenos Aires, Argentina, B1902COS
      • Framingham Centro Medico
    • Quilmes, Buenos Aires, Argentina, B1878GEG
      • Instituto de Investigaciones Clinicas Quilmes SRL
    • Quilmes, Buenos Aires, Argentina, B1878DVB
      • Instituto CER S.A
  • Tucumán
    • San Miguel De Tucumán, Tucumán, Argentina, T4000AXL
      • Centro Medico Privado de Reumatologia
    • San Miguel De Tucumán, Tucumán, Argentina, T4000AXL
      • Consultorio de Investigaciones Reumatologicas
• Greece
  • Athens, Greece, 115 27
    • Laiko General Hospital of Athens
  • Athens, Greece, 115 27
    • Athens General Hospital 'G Gennimatas
  • Larisa, Greece, 411 10
    • University General Hospital of Larissa
  • Thessaloníki, Greece, 546 36
    • Kianous Stavros
• India
  • Andhra Pradesh
    • Secunderabad, Andhra Pradesh, India, 500003
      • Krishna Institute of Medical Sciences
  • Gujarat
    • Ahmedabad, Gujarat, India, 380005
      • AES - AS - Panchshil Hospital - Ahmedabad
    • Sūrat, Gujarat, India, 395010
      • AES - AS - Unity Trauma Center and ICU - Unity Hospital - Surat
  • Karnataka
    • Hubli, Karnataka, India, 580021
      • AES - AS - Sushruta Multispeciality Hospital & Research Center Pvt Ltd - Hubli
  • Maharashtra
    • Nagpur, Maharashtra, India, 440012
      • Jasleen Hospital
• Mexico
  • Ciudad de Mexico, Mexico, 07760
    • Consultorio de Reumatologia
  • Distrito Federal, Mexico, 06760
    • AMAF Clinical Research,S.C.
  • Guadalajara, Mexico, 44600
    • Clinica de Investigacion en Reumatologia y Obesidad
  • Jalisco, Mexico, 44690
    • Centro de Estudios de Investigacion Basica Y Clinica SC
  • Baja California
    • Mexicali, Baja California, Mexico, 21200
      • Centro de Investigación en Artritis y Osteoporosis
  • Distrito Federal
    • San Miguel, Distrito Federal, Mexico, 11850
      • Centro de Investigación y Tratamiento Reumatológico S.C
  • Guanajuato
    • León, Guanajuato, Mexico, 37000
      • Morales Vargas Centro de Investigacion SC
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Bioclinica - Centro Integral En Reumatologia Sociedad Anónima de Capital Variable
    • Zapopan, Jalisco, Mexico, 45030
      • Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.
  • Yucatán
    • Merida, Yucatán, Mexico, 97000
      • Centro Peninsular de Investigacion S.C.P
• Poland
  • Bydgoszcz, Poland, 85-065
    • Nasz Lekarz Osrodek Badan Klinicznych
  • Lodzkie
    • Łódź, Lodzkie, Poland, 91-365
      • Centrym Medyczne AMED oddzial w Lodzi
  • Lubuskie
    • Nowa Sól, Lubuskie, Poland, 67-100
      • Twoja Przychodnia - Centrum Medyczne Nowa Sol
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Pratia MCM
    • Kraków, Malopolskie, Poland, 30-363
      • Centrum Medyczne Plejady
  • Mazowieckie
    • Nadarzyn, Mazowieckie, Poland, 05-830
      • NZOZ Lecznica MAK-MED
    • Warszawa, Mazowieckie, Poland, 00-874
      • Medycyna Kliniczna Marzena Waszczak-Jeka
    • Warszawa, Mazowieckie, Poland, 03-291
      • Centrum Medyczne AMED
  • Slaskie
    • Czestochowa, Slaskie, Poland, 42-200
      • Centrum Medyczne Czestochowa - PRATIA
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 61-545
      • Klinika Reumatologii i Rehabilitacji Ortopedyczno-Rehabilitacyjny Szpital Kliniczny im W. Degi
• Russian Federation
  • Kemerovo, Russian Federation, 650066
    • Belyayev Clinical Hospital of the Kuzbass
  • Moscow, Russian Federation, 111539
    • O.M. Filatov City Clinical Hospital #15
  • Smolensk, Russian Federation, 214025
    • Departmental Hospital at Smolensk Station "rzhd" JSC
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology Belgrade
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac
• Spain
  • A Coruña, Spain, 15006
    • Hospital Universitario A Coruña
  • Sevilla, Spain, 41010
    • Hospital Quironsalud Infanta Luisa
• Taiwan
  • Province Of China
    • Kaohsiung City, Province Of China, Taiwan, 81362
      • Kaohsiung Veterans General Hospital
    • Taipei, Province Of China, Taiwan, 100
      • National Taiwan University Hospital
    • Taoyuan, Province Of China, Taiwan, 333
      • Chang Gung Memorial Hospital, Linkou
• Ukraine
  • Kyïv, Ukraine, 04050
    • Limited Liability Company Medical Center Consilium
  • Poltava, Ukraine, 36024
    • ME Poltava Reg.Clin.Hospital n.a.M.V.Skliphosovskyi of Poltava Reg.Council
  • Zaporiz'ka Oblast
    • Zaporizhzhia, Zaporiz'ka Oblast, Ukraine, 69005
      • Medical Center of LLC Modern Clinic
• United States
  • California
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials Incorporated
  • Florida
    • Clearwater, Florida, United States, 33765-2616
      • Clinical Research of West Florida Inc - Clearwater
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research
    • Plantation, Florida, United States, 33324
      • IRIS Research and Development LLC
    • Tampa, Florida, United States, 33606-1246
      • Clinical Research of West Florida Inc - Tampa
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40504-2931
      • Bluegrass Community Research Inc
  • New York
    • Brooklyn, New York, United States, 11201
      • NYU Langone Ambulatory Care Brooklyn Heights
    • Manhasset, New York, United States, 11030-3816
      • Feinstein Institute for Medical Research
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28210-8509
      • DJL Clinical Research
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130-3483
      • Paramount Medical Research and Consulting LLC
  • Texas
    • Austin, Texas, United States, 78745-1485
      • Tekton Research Inc
    • Colleyville, Texas, United States, 76034-5913
      • Precision Comprehensive Clinical Research Solutions
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center
    • Mesquite, Texas, United States, 75150
      • SouthWest Rheumatology Research, LLC
  • Virginia
    • Danville, Virginia, United States, 24541-1222
      • Spectrum Medical, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years to ≤ 70 years
• Willing and able to understand and provide written informed consent.
• Fulfill the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for SLE
• Disease duration of at least 6 months

• Active SLE as indicated by presence of all the following:

  1. SLEDAI-2K total score ≥ 6 at Screening, excluding fever, SLE headache, or organic brain syndrome.
  2. SLEDAI-2K total score ≥ 4, excluding points attributable to any urine or laboratory results, immunologic measures, fever, SLE headache, or organic brain syndrome at Screening and Baseline (Day 1).
  3. At least one of the following BILAG 2004 Index levels of disease at Screening:
• BILAG A disease in ≥ 1 organ system
• BILAG B disease in ≥ 2 organ systems d. PGA score ≥ 1 on a 0 to 3 visual analog scale (VAS) at Screening

Have at least one of the following at Screening per central lab:

• ANA ≥ 1:80
• Anti-dsDNA antibodies elevated to above normal range as established by the central laboratory (ie, positive results)

• Anti-Smith antibodies elevated to above normal (ie, positive results) Ongoing treatment for SLE

  1. Treatment with one or more disease-modifying anti-rheumatic drug (DMARD) or immunosuppressive medication: Any of the following medications each administered at conventional anti-rheumatic doses for treatment of SLE for at least 12 weeks before Screening (unless discontinued or dose adjusted for documented drug-related toxicity or size/weight), and at a stable dose (including route of administration) for a minimum of 8 weeks prior to Screening and maintained through Baseline (Day 1):

  2. Treatment with OGC monotherapy (without the concomitant use of DMARDs or immunosuppressants):

     • Average daily dose of PO prednisone ≥ 10 mg but ≤ 40 mg (or prednisone equivalent) for a minimum of 4 weeks prior to Screening and a stable dose for minimum of 2 weeks prior to Screening. The dose of OGC must be kept for a minimum of 2 weeks prior to Randomization. Daily dosing or alternate day dosing of PO prednisone or equivalent is allowed.
• Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Randomization.
• Non-sterilized male participants who are sexually active with a woman partner of childbearing potential must agree to use a condom with spermicide from Randomization and until 3 months (approximately 5 half-lives) after receipt of the last dose.

Exclusion Criteria:

• Any condition that, in the opinion of the Investigator, or the Sponsor/Central Review Committee, would interfere with the evaluation of the IP or interpretation of participant safety or study results (including borderline disease activity)
• History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or a previous mAb or human Ig therapy
• Active LN or active severe or unstable neuropsychiatric SLE
• Current diagnosis of non-SLE vasculitis syndrome, mixed connective tissue disease, or rheumatic (overlap) syndrome
• Participation in another clinical study with an investigational drug within 4 weeks before Day 1
• Breastfeeding or pregnant women or women who intend to become pregnant anytime from signing the ICF through 6 months after receiving the last dose of IP
• Major surgery within 8 weeks prior to Screening or elective surgery planned from Screening through Day 393.
• Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks before Screening
• Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection
• Hepatitis B, Hepatitis C, active TB, any severe herpes infection, clinically active infection, or opportunistic infection
• History of clinically significant cardiac disease including unstable angina; and/or myocardial infarction and/or congestive heart failure within 6 months prior to Randomization.
• History of cancer within the past 5 years except, in situ carcinoma of the cervix, cutaneous basal cell or squamous cell carcinoma with curative therapy.
• Receipt of a live-attenuated vaccine within 4 weeks before Day 1 Administration of inactivated (killed) vaccines is acceptable
• The use of immunosuppressants, biologics and DMARDS within the protocol defined washout periods

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
Experimental: VIB7734 SC (dosing interval 1)	Drug: VIB7734; VIB7734; Other Names: HZN-7734; Daxdilimab
Experimental: VIB7734 SC (dosing interval 2)	Drug: VIB7734; VIB7734; Other Names: HZN-7734; Daxdilimab
Placebo Comparator: Placebo SC (dosing interval 3)	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving a BILAG-2004 Index-based Combined Lupus Assessment (BICLA) Response and an OGC Dose ≤ 7.5 mg/Day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48	A BICLA response required improvement in all domains affected at baseline, assessed by the BILAG 2004, no worsening of other BILAG 2004 domains, no worsening of SLEDAI-2K or PGA scores compared with baseline, no use of restricted medications beyond the protocol-allowed threshold, and no discontinuation of IP.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) Score ≥ 10 at Baseline Achieving ≥ 50% Reduction From Baseline in CLASI-A Score at Week 12	The CLASI-A evaluates erythema (0-3 [higher scores indicate more severe redness]), scale/hypertrophy (0-2 [higher scores indicate more extensive scaling/thickening]), mucous membrane lesions (0 [absent] or 1 [present]), recent hair loss (0 [absent] or 1 [present]), and non-scarring alopecia (0-3 [(higher scores indicate more extensive hair loss without scarring]) at 13 anatomical sites on the skin. Total score is calculated by summing scores across all anatomical locations for each parameter. Higher total scores indicate greater disease activity and severity in SLE. Reduction of 50% in CLASI-A score was defined by meeting all the following conditions: A ≥ 50% reduction of CLASI-A score at Week 12 as compared to baseline.; No use of restricted medications beyond the protocol-allowed threshold before assessment.; No discontinuation of IP.	Week 12
Number of Participants Achieving an SLE Responder Index (SRI)-4 Response and an OGC Dose ≤ 7.5 mg/Day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48	The SRI-4 measures reduction in SLE disease activity and it is a composite measure that includes the SLEDAI-2K, BILAG-2004, and PGA. SRI responder was defined by meeting all of the following criteria: 1) Reduction of ≥4 points from baseline in SLEDAI-2K score; 2) no new BILAG A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [0-3 scale] from baseline) in the PGA.	Week 48
Number of Participants With an OGC Dose ≥ 10 mg/Day of Prednisone or Equivalent at Baseline Who Maintained an OGC Dose ≤ 7.5 mg/Day From Week 36 Through Week 48	Maintenance of OGC reduction from Week 36 to Week 48 was defined by meeting all the following criteria: Achieved an OGC dose of ≤ 7.5 mg/day prednisone or equivalent at Week 36; Maintained an OGC dose of ≤ 7.5 mg/day from Week 36 through Week 48; No use of restricted medications beyond the protocol-allowed threshold before assessment; No discontinuation of IP before assessment	Week 36 up to Week 48
Number of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 48	LLDAS was defined by meeting all of the following criteria: SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity measured as maintaining a D (no disease activity but suggests the system had previously been affected) or E (no current or previous disease activity) score in BILAG Gastrointestinal Body System; No new lupus disease activity compared with the previous; Physician's Global Assessment of Disease Activity ≤ 1 on a 3-point visual analog scale from no disease activity to severe disease activity; A current prednisolone (or equivalent) dose ≤ 7.5 mg daily; Well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents	Week 48
Serum Concentration of Daxdilimab		Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab	A baseline ADA-positive participant was defined as a participant who had an ADA positive sample at baseline. ADA incidence is the number of the participants ADA positive post-Baseline only or who boosted their preexisting ADA (≥ 4 × Baseline level) during the trial. Persistent positive was defined as ADA positive at ≥ 2 post-Baseline assessments (with ≥ 16 weeks between first and last positive) or positive at last post-Baseline assessment. Transient positive was defined as ADA post-Baseline positive but did not fulfill the criteria of persistent positive.	Baseline to Week 56
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood		Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 32, Week 36, Week 44, Week 48, Week 52, Week 56
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence associated with the use of an intervention in humans whether or not it is considered intervention-related. TEAEs are AEs that started on or after the first dose of IP. An AE was considered serious (SAE) if it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolonged existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital abnormality/birth defect, or an important medical event. AE severity was rated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).	Up to Week 56
Number of Participants Who Experienced AEs of Special Interest (AESI)	An AESI is an AE of scientific and medical interest specific to understanding of the IP and may require close monitoring and collection of additional information by the Investigator. AESIs for this study included: Hypersensitivity reaction, including anaphylaxis.; Severe (Grade 3 or higher) viral infections/reactivations.; Opportunistic infection.; Malignancy (except non-melanoma skin cancer).	Up to Week 56

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants who experience AEs, SAEs, AESIs	Safety evaluation will occur throughout the study.	Baseline through Week 56

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen; Study Director: Nisha Jain, MD, Horizon Therapeutics

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Actual): May 16, 2023
• Study Completion (Actual): June 9, 2023

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 14, 2021

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 21, 2024
• Last Verified: July 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: VIB7734.P2.S1; 2020-005528-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No