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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 195
- 试验地点
- 9
- 主要终点
- Proportion of Participants who achieve BICLA and OGC (oral glucocorticoid) reduction response at Week 48.
研究概览
简要总结
Data from Phase 2 studies with interferon (IFN)α-blocking agents and a plasmacytoid dendritic cell (pDC) antagonist have demonstrated improvement in systemic lupus erythematosus (SLE) or cutaneous lupus disease activity, supporting the rationale for blocking the IFN pathways and pDCs in patients with SLE. Given the lack of highly efficacious and safe treatments for active SLE and the significant impact of this disease on health-related quality of life, there is currently a significant unmet need for new targeted therapies. Based on its mechanism of action (binding to immunoglobulin-like transcript 7 on the surface of pDCs, thus inducing apoptosis and reduction in the number of pDCs), VIB7734 has the potential to decrease SLE disease activity. In addition, based on data currently available, VIB7734 presents an acceptable safety profile, and hence it is justified to evaluate its potential efficacy in patients with active SLE.
In this study, approximately 195 participants will be randomized in a ratio of 1:1:1 (65 participants per group) to receive VIB7734 200 mg Q4W SC, VIB7734 200 mg every 12 weeks (Q12W) SC, with an additional 200 mg SC dose at Week 4, or placebo. To maintain blinding, participants randomized to the VIB7734 200 mg Q12W SC dosing regimen will receive SC placebo injections on dosing visits outside the Q12W schedule. Randomization will be stratified by SLE Disease Activity Index 2000 (SLEDAI-2K) total score at Screening (≥ 10 or < 10) and prednisone or equivalent oral GC (OGC) dose at Baseline (Day 1) (≥ 10 mg or < 10 mg).
Adults aged ≥ 18 to ≤ 70 years who have moderate to severely active (recent flares or chronic active disease) SLE as defined by the SLE Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG) 2004 Index, and Physician Global Assessment (PGA). Stabilization of the SLE treatment regimen in SLE participants prior to Baseline (Day 1) decreases the confounding of the study results by the SoC (ie, changes in disease activity post- Baseline [Day 1] are more likely to be attributable to the introduction of VIB7734, rather than a change in background therapy).
Rationale for study population: Severe central nervous system (CNS) lupus and LN may be less responsive to therapy than other manifestations or may require different treatment regimens (eg, cyclophosphamide, IV Ig, highdose mycophenolate) than typically used in extrarenal SLE. Therefore, these individuals will be excluded from participating in this study. Also, individuals with significantly impaired renal function are excluded since they may have advanced, fixed disease that will not be responsive to therapy, and furthermore, these individuals are at higher risk for AEs. A urine protein: creatinine ratio (UPCr) of up to 3 mg/mg is allowed. This limit is applied because higher levels of proteinuria increase the risk of AEs.
Outcomes:
1.Primary Objectives : To evaluate the effect of VIB7734 compared to placebo in reducing SLE disease activity at Week 48 in participants treated with standard of care therapy.
Outcome measure : Proportion of participants achieving a BILAG 2004 Index-based Combined Lupus Assessment (BICLA) response and an oral glucocorticoid (OGC) dose ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose of prednisone or equivalent at Week 48.
2. Secondary Objectives:
a. To evaluate the effect of VIB7734 compared with placebo to reduce cutaneous disease activity at Week 12.
Outcome measure : Proportion of participants with Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity (CLASI-A) score ≥ 10 at Baseline (Day 1) who achieve ≥ 50% reduction from Baseline (Day 1) in CLASI-A score at Week 12.
b. To evaluate the effect of VIB7734 compared with placebo to reduce SLE disease activity at Week 48.
Outcome measure : Proportion of participants achieving a Systemic Lupus Responder Index (SRI)-4 response and an OGC dose ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose of prednisone or equivalent at Week 48.
c. To evaluate the effect of VIB7734 compared with placebo on sustained OGC reduction from Week 36 to Week 48.
Outcome measure : Proportion of participants at OGC dose ≥ 10 mg prednisone or equivalent at Baseline (Day 1) who achieve OGC dose ≤ 7.5 mg/day prednisone or equivalent at Week 36 and maintained through Week 48.
d. To evaluate the effect of VIB7734 compared with placebo to achieve low disease activity at Week 48.
Outcome measure : Proportion of participants achieving Lupus Low Disease Activity State at Week 48.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •1 Age ≥ 18 years to ≤ 70 years.
- •2 Willing and able to understand and provide written informed consent.
- •3 Fulfill the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for SLE 4 Disease duration of at least 6 months.
- •5 Active SLE as indicated by presence of all the following: a) SLEDAI-2K total score ≥ 6 at Screening, excluding fever, SLE headache, or organic brain syndrome.
- •b) 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).
- •c) 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: i)ANA ≥ 1:80 ii)Anti-dsDNA antibodies elevated to above normal range as established by the central laboratory (ie, positive results) iii)Anti-Smith antibodies elevated to above normal (ie, positive results) 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.
排除标准
- •1 Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the IP or interpretation of participant safety or study results.
- •2 History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or a previous mAb or human Ig therapy.
- •3 Active LN or active severe or unstable neuropsychiatric SLE.
- •4 Current diagnosis of non-SLE vasculitis syndrome, mixed connective tissue disease, or rheumatic (overlap) syndrome.
- •5 Participation in another clinical study with an investigational drug within 4 weeks before Day
- •6 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.
- •7 Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks before Screening.
- •8 Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection.
- •9 Hepatitis B, Hepatitis C, active TB, any severe herpes infection, clinically active infection, or opportunistic infection.
- •10 History of clinically significant cardiac disease.
- •14 The use of immunosuppressants, biologics and DMARDS within the protocol defined washout periods.
结局指标
主要结局
Proportion of Participants who achieve BICLA and OGC (oral glucocorticoid) reduction response at Week 48.
时间窗: Week 48
Participants will have BICLA (BILAG 2004 Index-Based Combined Lupus Assessment)
时间窗: Week 48
and oral glucocorticoid assessment at week 48.
时间窗: Week 48
次要结局
- Proportion of Participants with CLASI-A score ≥ 10 at Baseline (Day 1) who achieve ≥ 50% reduction from Baseline (Day 1) in CLASI-A score at Week 12.(Cutaneous Lupus Erythematosus Disease Area and Severity Index will be measured at week 12. The scoring consists of 2 parts: inflammatory activity of the disease and damage done by the disease.)
- Proportion of Participants achieving an SRI-4 response and an OGC dose ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose of prednisone or equivalent at Week 48.(The SRI-4 (SLE Responder Index) is defined as meeting all criteria compared to baseline, (e.g. no worsening of symptoms).)
- Proportion of Participants at OGC dose ≥ 10 mg prednisone or equivalent at Baseline (Day 1) who achieve an OCG of ≤ 7.5 mg/day prednisone or equivalent at Week 36 through Week 48.
- Proportion of Participants achieving LLDAS (Lupus Low Disease Activity State) at Week 48.(LLDAS is a composite measure of SLE disease activity that measures 5 criteria: SLEDAI-2K ≤ 4, with no activity in major organ systems, no new lupus disease activity, PGA ≤ 1 (scale 0 to 3), current prednisone (or equivalent) dose ≤ 7.5 mg daily, tolerated maintenance doses of immunosuppressive drugs and approved biological agents)