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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
214
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.
Time frame: Week 48
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: 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.
Time frame: 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.
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Inland Rheumatology Clinical Trials Incorporated
Upland, California, United States
Clinical Research of West Florida Inc - Clearwater
Clearwater, Florida, United States
Millennium Research
Ormond Beach, Florida, United States
IRIS Research and Development LLC
Plantation, Florida, United States
Clinical Research of West Florida Inc - Tampa
Tampa, Florida, United States
Emory University School of Medicine
Atlanta, Georgia, United States
Bluegrass Community Research Inc
Lexington, Kentucky, United States
NYU Langone Ambulatory Care Brooklyn Heights
Brooklyn, New York, United States
Feinstein Institute For Medical Research
Manhasset, New York, United States
SUNY Upstate Medical Center
Syracuse, New York, United States
...and 57 more locations
Time frame: 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: 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
Time frame: 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: 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
Time frame: Week 48
Serum Concentration of Daxdilimab
Time frame: 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.
Time frame: Baseline to Week 56
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood
Time frame: 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).
Time frame: 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: 1. Hypersensitivity reaction, including anaphylaxis. 2. Severe (Grade 3 or higher) viral infections/reactivations. 3. Opportunistic infection. 4. Malignancy (except non-melanoma skin cancer).
Time frame: Up to Week 56