Study of VIB7734 for the Treatment of Moderate to Severely Active SLE

Phase 2

Completed

Conditions: Lupus Erythematosus, Systemic

Interventions: Drug: VIB7734
Other: Placebo

Registration Number: NCT04925934

Lead Sponsor: Amgen

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 214

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VIB7734 SC (dosing interval 2)	VIB7734	-
Placebo SC (dosing interval 3)	Placebo	-
VIB7734 SC (dosing interval 1)	VIB7734	-

Primary Outcome Measures

Name	Time	Method
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	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.

Secondary Outcome Measures

Name	Time	Method
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	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: 1. A ≥ 50% reduction of CLASI-A score at Week 12 as compared to baseline. 2. No use of restricted medications beyond the protocol-allowed threshold before assessment. 3. No discontinuation of IP.
Number of Participants Who Experienced AEs of Special Interest (AESI)	Up to Week 56	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: 1. Hypersensitivity reaction, including anaphylaxis. 2. Severe (Grade 3 or higher) viral infections/reactivations. 3. Opportunistic infection. 4. Malignancy (except non-melanoma skin cancer).
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 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	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.
Number of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 48	Week 48	LLDAS was defined by meeting all of the following criteria: 1. 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 2. No new lupus disease activity compared with the previous 3. Physician's Global Assessment of Disease Activity ≤ 1 on a 3-point visual analog scale from no disease activity to severe disease activity 4. A current prednisolone (or equivalent) dose ≤ 7.5 mg daily 5. Well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents
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	Baseline to Week 56	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.
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	Week 36 up to Week 48	Maintenance of OGC reduction from Week 36 to Week 48 was defined by meeting all the following criteria: 1. Achieved an OGC dose of ≤ 7.5 mg/day prednisone or equivalent at Week 36 2. Maintained an OGC dose of ≤ 7.5 mg/day from Week 36 through Week 48 3. No use of restricted medications beyond the protocol-allowed threshold before assessment 4. No discontinuation of IP before assessment
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	Up to Week 56	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).

Trial Locations

Locations (67): Millennium Research
🇺🇸
Ormond Beach, Florida, United States
Inland Rheumatology Clinical Trials Incorporated
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Upland, California, United States
Clinical Research of West Florida Inc - Clearwater
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Clearwater, Florida, United States
IRIS Research and Development LLC
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Plantation, Florida, United States
Clinical Research of West Florida Inc - Tampa
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Tampa, Florida, United States
Emory University School of Medicine
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Atlanta, Georgia, United States
Bluegrass Community Research Inc
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Lexington, Kentucky, United States
NYU Langone Ambulatory Care Brooklyn Heights
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Brooklyn, New York, United States
SUNY Upstate Medical Center
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Syracuse, New York, United States
DJL Clinical Research
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Charlotte, North Carolina, United States
Paramount Medical Research and Consulting LLC
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Middleburg Heights, Ohio, United States
Tekton Research Inc
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Austin, Texas, United States
Metroplex Clinical Research Center
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Dallas, Texas, United States
Precision Comprehensive Clinical Research Solutions
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Colleyville, Texas, United States
Southwest Rheumatology Research, LLC
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Mesquite, Texas, United States
Spectrum Medical, Inc
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Danville, Virginia, United States
Consultorios Médicos Dr. Doreski
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Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Clínica Adventista Belgrano
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Estomba, Buenos Aires, Argentina
Framingham Centro Médico
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La Plata, Buenos Aires, Argentina
Instituto de Investigaciones Clinicas Quilmes SRL
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Quilmes, Buenos Aires, Argentina
Consultorio de Investigaciones Reumatologicas
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San Miguel De Tucumán, Tucumán, Argentina
Athens General Hospital 'G Gennimatas
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Athens, Greece
Laiko General Hospital of Athens
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Athens, Greece
University General Hospital of Larissa
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Larisa, Greece
Kianous Stavros
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Thessaloníki, Greece
AES - AS - Panchshil Hospital - Ahmedabad
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Ahmedabad, Gujarat, India
Krishna Institute of Medical Sciences
🇮🇳
Secunderabad, Andhra Pradesh, India
AES - AS - Sushruta Multispeciality Hospital & Research Center Pvt Ltd - Hubli
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Hubli, Karnataka, India
Klinika Reumatologii i Rehabilitacji Ortopedyczno-Rehabilitacyjny Szpital Kliniczny im W. Degi
🇵🇱
Poznań, Wielkopolskie, Poland
Morales Vargas Centro de Investigacion SC
🇲🇽
León, Guanajuato, Mexico
AES - AS - Unity Trauma Center and ICU - Unity Hospital - Surat
🇮🇳
Sūrat, Gujarat, India
Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.
🇲🇽
Zapopan, Jalisco, Mexico
Jasleen Hospital
🇮🇳
Nagpur, Maharashtra, India
Bioclinica - Centro Integral En Reumatologia Sociedad Anónima de Capital Variable
🇲🇽
Guadalajara, Jalisco, Mexico
Centro Peninsular de Investigacion S.C.P
🇲🇽
Merida, Yucatán, Mexico
Consultorio de Reumatologia
🇲🇽
Ciudad de Mexico, Mexico
Clinica de Investigacion en Reumatologia y Obesidad
🇲🇽
Guadalajara, Mexico
Centro de Estudios de Investigacion Basica Y Clinica SC
🇲🇽
Jalisco, Mexico
Centrym Medyczne AMED oddzial w Lodzi
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Łódź, Lodzkie, Poland
Pratia MCM
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Krakow, Malopolskie, Poland
Twoja Przychodnia - Centrum Medyczne Nowa Sol
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Nowa Sól, Lubuskie, Poland
Medycyna Kliniczna Marzena Waszczak-Jeka
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Warszawa, Mazowieckie, Poland
Centrum Medyczne AMED
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Warszawa, Mazowieckie, Poland
Centrum Medyczne Plejady
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Kraków, Malopolskie, Poland
Centrum Medyczne Czestochowa - PRATIA
🇵🇱
Czestochowa, Slaskie, Poland
Nasz Lekarz Osrodek Badan Klinicznych
🇵🇱
Bydgoszcz, Poland
O.M. Filatov City Clinical Hospital #15
🇷🇺
Moscow, Russian Federation
Belyayev Clinical Hospital of the Kuzbass
🇷🇺
Kemerovo, Russian Federation
Departmental Hospital at Smolensk Station "rzhd" JSC
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Smolensk, Russian Federation
Institute of Rheumatology Belgrade
🇷🇸
Belgrade, Serbia
Military Medical Academy
🇷🇸
Belgrade, Serbia
University Clinical Center Kragujevac
🇷🇸
Kragujevac, Serbia
Hospital Universitario A Coruña
🇪🇸
A Coruña, Spain
Hospital Quironsalud Infanta Luisa
🇪🇸
Sevilla, Spain
National Taiwan University Hospital
🇨🇳
Taipei, Province Of China, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳
Taoyuan, Province Of China, Taiwan
Medical Center of LLC Modern Clinic
🇺🇦
Zaporizhzhia, Zaporiz'ka Oblast, Ukraine
Limited Liability Company Medical Center Consilium
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Kyïv, Ukraine
Feinstein Institute For Medical Research
🇺🇸
Manhasset, New York, United States
Centro de Investigación en Artritis y Osteoporosis
🇲🇽
Mexicali, Baja California, Mexico
NZOZ Lecznica MAK-MED
🇵🇱
Nadarzyn, Mazowieckie, Poland
Kaohsiung Veterans General Hospital
🇨🇳
Kaohsiung City, Province Of China, Taiwan
ME Poltava Reg.Clin.Hospital n.a.M.V.Skliphosovskyi of Poltava Reg.Council
🇺🇦
Poltava, Ukraine
Instituto CER S.A
🇦🇷
Quilmes, Buenos Aires, Argentina
AMAF Clinical Research,S.C.
🇲🇽
Distrito Federal, Mexico
Centro de Investigación y Tratamiento Reumatológico S.C
🇲🇽
San Miguel, Distrito Federal, Mexico
Centro Medico Privado de Reumatologia
🇦🇷
San Miguel De Tucumán, Tucumán, Argentina