A Multi-center, Randomized, Participant- and Investigator- Blinded, Placebo-controlled, Parallel Group Basket Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjögren's Syndrome or Mixed Connective Tissue Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- MCTD Participants: Change From Baseline in Physician's Global Assessment Scale (PhGA) After 24 Weeks of Treatment
研究概览
简要总结
This study was a basket trial designed to establish safety, tolerability and efficacy of MHV370 in Sjögren's Syndrome (SjS) and Mixed Connective Tissue Disease (MCTD).
详细描述
This was a randomized, participant and investigator blinded, placebo-controlled, multi center parallel group basket study to evaluate the safety, tolerability and efficacy of MHV370 in participants with Sjögren's Syndrome (SjS) or with Mixed Connective Tissue Disease (MCTD). Participants first underwent a screening period of up to 6 weeks, followed by a treatment duration of 24 weeks and a follow-up period of 4 weeks. Total study duration for each participant was up to 34 weeks. Participants with SjS were randomized in a 1:1 ratio to MHV370 or placebo and participants with MCTD were randomized in a 1:1 ratio to MHV370 or placebo.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SjS and MCTD:
- •Fully vaccinated with any locally approved COVID-19 vaccination including booster vaccinations if required by local guidelines
- •Unstimulated whole salivary flow rate of > 0 mL/min at screening
- •Classification of Sjögren's Syndrome according to the 2016 ACR/EULAR criteria at screening
- •Screening ESSDAI (based on weighted score) ≥ 5 from 8 defined domains (biologic, hematologic, articular, cutaneous, glandular, lymphadenopathy, renal, constitutional).
- •Diagnosis of MCTD based on criteria like a) Raynaud's phenomenon b) At least two of the four following signs: i) synovitis, ii) myositis, iii) swollen fingers and vi) interstitial lung disease
- •Patients with overlap syndromes, i.e. patients meeting diagnostic criteria for systemic autoimmune disease other than MCTD may be included unless they have major organ involvement as judged by the investigator
排除标准
- •SjS and MCTD:
- •Prior use of B-cell depleting therapy within 6 months of baseline. For participants who received B-cell depleting therapy within 6 -12 months of baseline visit, B-cell count should be within normal range
- •Prior treatment with any of the following within 3 months of baseline: CTLA4-Fc Ig (abatacept), Anti-TNF mAb, Intravenous Ig, Plasmapheresis, i.v. or oral cyclophosphamide, i.v. or oral cyclosporine A
- •Screening CBC laboratory values as follows: Hemoglobin levels < 8 g/dL (< 5 mmol/L), Total leukocyte count < 2,000/µL (2 x 109/L), Platelets < 50,000/µL (50 x 109/L), Neutrophil count < 1,000/µL (1 x 109/L)
- •Pregnant or nursing (lactating) women
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they use a highly effective method of contraception
- •Sjögren's Syndrome overlap syndromes where another autoimmune disease constitutes the primary illness
- •Required regular use of medications known to cause, as a major side effect, dry mouth / eyes
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
SjS participants: MHV370
SjS participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks. Double-blind supply will be used.
干预措施: MHV370 (Drug)
SjS participants: Placebo
SjS participants randomized in the placebo arm will be treated with placebo for 24 weeks. Double-blind supply will be used.
干预措施: Placebo (Drug)
MCTD participants: MHV370
MCTD participants randomized in the MHV370 arm will be treated with MHV370 for 24 weeks. Double-blind supply will be used.
干预措施: MHV370 (Drug)
MCTD participants: Placebo
MCTD participants randomized in the placebo arm will be treated with placebo for 24 weeks. Double-blind supply will be used.
干预措施: Placebo (Drug)
结局指标
主要结局
MCTD Participants: Change From Baseline in Physician's Global Assessment Scale (PhGA) After 24 Weeks of Treatment
时间窗: Baseline, Week 24
The physician's global assessment scale is used for the Investigator to rate the disease activity of their patient using 100 mm visual analog scale (VAS) ranging from "no disease activity" (0) to "maximal disease activity" (100). A negative change score from baseline indicates improvement. Only participants with evaluable records are included.
SjS Participants: Change From Baseline in Eular Sjögren's Disease Activity Index (ESSDAI) After 24 Weeks of Treatment
时间窗: Baseline, Week 24
The ESSDAI is an established disease outcome measure for Sjögren's syndrome that classifies disease activity in 3-4 levels according to their severity (i.e., no, low, moderate, high), over each of 12 organ-specific domains. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The score range is 0 - 123, where a higher ESSDAI score indicates more severe symptoms. A negative change score from baseline indicates improvement.
次要结局
- SjS and MCTD Participants: Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours (AUC0-6h) of MHV370(pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4)
- SjS and MCTD Participants: Maximum Observed Plasma Concentrations (Cmax) of MHV370 at Steady State(pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4)
- SjS and MCTD Participants: Change From Baseline in Physician Global Assessment (PhGA)(Baseline, Weeks 4, 8, 12, 20 and 24)
- MCTD: Change From Baseline in Articular and Pulmonary Domains of the Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)(Baseline, Weeks 4, 8, 12 and 24)
- SjS and MCTD Participants: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale(Baseline, Weeks 4, 8, 12, 20 and 24)
- MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Two Seconds (FEV2) of a Forced Breath(Baseline, Week 12)
- MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Three Seconds (FEV3) of a Forced Breath(Baseline, Week 12)
- MCTD Participants: Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD)(Baseline, Weeks 4, 8, 12 and 24)
- SjS and MCTD Participants: Time to Reach Maximum Plasma Concentrations (Tmax) of MHV370 at Steady State(pre-dose, 0.5, 1, 2 ,4 and 6 hours after dosing at week 4)
- SjS Participants: Change From Baseline to the Salivary Flow Rate(Baseline, Weeks 4, 12 and 24)
- MCTD Participants: Change From Baseline in Forced Vital Capacity (FVC)(Baseline, Week 12)
- MCTD Participants: Change From Baseline in Forced Expiratory Volume During the First Second (FEV1) of a Forced Breath(Baseline, Week 12)
- MCTD Participants: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)(Baseline, Week 24)
- SjS Participants: Change From Baseline in Eular Sjögren's Syndrome Disease Activity Index (ESSDAI)(Baseline, Weeks 4, 8, 12, 20 and 24)
- SjS Participants: Change From Baseline in Eular Sjögren's Syndrome Patient Reported Index (ESSPRI)(baseline, weeks 4, 8, 12, 20 and 24)
- SjS Participants: Change From Baseline to the Schirmer's Test(Baseline, Week 4, 12 and 24)
- SjS Participants: Sjögren's Tool for Assessing Response (STAR) Response Over Time up to Week 24(Baseline, Week 4, 12 and 24)
- MCTD Participants: Change From Baseline in Raynaud's Condition Score (RCS)(Baseline, Weeks 4, 12 and 24)