A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Neutralization of the Interferon Gene Signature and the Clinical Efficacy of IFNα-Kinoid in Adult Subjects With Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Neovacs
- 入组人数
- 185
- 试验地点
- 103
- 主要终点
- Percent Change From Baseline in IFN Gene Signature at W36
研究概览
简要总结
The safety and immunogenicity of the IFNα-Kinoid (IFN-K) have been evaluated in a phase I clinical study conducted in subjects with Systemic Lupus Erythematosus (SLE). Preliminary results showed acceptable safety profile and patients developped antibodies response.
The principal aim of the present study is to confirm the neutralization of the interferon gene signature and the clinical efficacy of IFN-K in subjects with SLE. In addition, the immune responses and the safety elicited by IFN-K will also be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has had a diagnosis of SLE according to current American College of Rheumatology (ACR) criteria (4 of 11 ACR criteria)
- •Has SLEDAI-2K ≥ 6
- •Has at least 1 BILAG A and/or at least 2 BILAG B
- •Has a positive IFN gene signature by reverse transcription quantitative polymerase chain reaction (RT-qPCR)
- •Has anti-nuclear antibodies (ANA) ≥ 1:160 and/or anti-dsDNA antibodies ≥ 7.0 IU/mL
- •Currently receiving at least one treatment for SLE
排除标准
- •Has active, severe lupus nephritis as defined either by the immediate need for cyclophosphamide treatment or by renal BILAG A
- •Has active, severe, neuropsychiatric SLE, defined as neuropsychiatric BILAG A
- •Has been treated with corticosteroids (CS) at a dose of >20 mg of prednisone equivalent/day for > 7 consecutive days
- •Is currently receiving or has received pulse dose CS (≥ 250 mg prednisone equivalent/day)
- •Has received potent immunosuppressive drugs
- •Has received abatacept, sifalimumab, rontalizumab, anifrolumab, belimumab, tumor necrosis factor (TNF) antagonists or another registered or investigational biological therapy
- •Has received anti-B-cell therapy (e.g., rituximab, epratuzumab)
- •Has frequent recurrences of oral or genital herpes simplex lesions
- •Is at high risk of significant infection and/or has any current signs or symptoms of infection at entry or has received intravenous antibiotics
- •Has received any live vaccine
- •Has used any investigational or non-registered product or any investigational or non-registered vaccine
- •Is high-risk human papilloma virus (HPV) positive by rRT-qPCR on a cervical swab
- •Has cytological abnormalities ≥ high grade squamous intraepithelial lesions (HSIL) on a cervical swab
结局指标
主要结局
Percent Change From Baseline in IFN Gene Signature at W36
时间窗: Baseline and Last Available Value (LVA) between week 24 and week 36
The biological endpoint aimed at evaluating the neutralization of the IFN gene signature following treatment with IFN-K compared to placebo, as measured by the % change from baseline of the expression of IFN-induced genes.
Number of Participants Who Achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) With Superimposed CS Tapering at Week 36
时间窗: At Week 36
British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responder was defined as a subject who had the following criteria at week 36: * All BILAG A scores at baseline improve to B/C/D and all BILAG B scores improve to C/D at W36, and * No BILAG worsening in other body systems: no new BILAG A or ≥ 2 new BILAG B scores at W36, and * No worsening in SLEDAI-2K total score at W36 compared with baseline, and * No deterioration in Physician Global Assessment (PGA) (\< 10% worsening) on Visual Analog Scale (VAS) 100 mm at W36 compared with baseline, and * No addition or increased dose level of anti-malarial drugs or immunosuppressive drugs or CS\* between W24 and W36 (\*≤5 mg prednisolone or equivalent /day at W24 and no increase until W36).
次要结局
- Number of Participants With Neutralizing Anti-IFN-alpha Antibodies at W36(At week 36)
- Number of Participants Who Achieved a Composite SRI-4 Including CS ≤5mg/Day at Week 36(At Week 36)
- Number of Participants With Treatment-related Adverse Events(9 months)
- CLASI Total Activity Change From Baseline at Week 36(Baseline and Week 36)
- Number of Participants Who Achieved a Composite SRI-4 Including CS ≤7,5mg/Day at Week 36(At Week 36)
- Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) at Week 36(At Week 36)
- SELENA-SLEDAI - Change From Baseline to Week 36(Baseline and Week 36)
- SLICC/ACR-DI Change From Baseline at Week 36(Baseline and Week 36)
- Number of Participants Who Achieved a Systematic Lupus Erythematosus (SLE) Responder Index (SRI)-4 at Week 36(W36 (9 months))
- BILAG Global Score Change From Baseline to Last Available Value (LVA) Between Week 24 and Week 36(Last Available Value (LVA) between week 24 and week 36)