A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2a/b Study Assessing the Efficacy, Safety and Tolerability of DDY391 in Participants With Sjögren's Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 344
- 试验地点
- 9
- 主要终点
- Part A and B: Change from baseline in ESSDAI score
研究概览
简要总结
To evaluate efficacy, safety, and tolerability of DDY391 up to 52 weeks in participants with Sjögren's disease (SjD) and to determine the dose response relationship of DDY391 in participants with SjD, to support dose selection for Phase 3.
详细描述
This study is a Phase 2a/b, randomized, double-blind, placebo-controlled, multi-center trial involving participants with SjD. The study consists of three parts (Part A, Part B, and Part C).
The study includes a screening period of up to 8 weeks to assess eligibility, a 52-week treatment period, and a 4-week safety follow-up period after the last dose of study treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a diagnosis of SjD according to the ACR/EULAR 2016 classification criteria at screening:
- •- Positive anti-Ro (SSA) antibodies at screening. Participants negative for anti-Ro/SSA antibodies are eligible if they have documented previous biopsy showing evidence of salivary gland inflammation consistent with SjD.
排除标准
- •Presence of another autoimmune rheumatic disease that is active at screening and constitutes the principal illness.
- •Exclusion based on medications being used for SjD:
- •Participants taking > 400 mg/day hydroxychloroquine are excluded. Participants taking ≤400 mg/day hydroxychloroquine should be on a stable dose for at least 4 weeks prior to randomization.
- •Participants taking > 400 mg/day hydroxychloroquine are excluded. Participants on ≤ 400 mg/day of hydroxychloroquine should be on a stable dose for at least 4 weeks prior to randomization.
- •Prior treatment with any of the following within 3 months prior to randomization: belimumab, abatacept, anti-tumor necrosis factor alpha biologic agents, immunoglobulins, plasmapheresis, intravenous (i.v.) or oral cyclophosphamide, mycophenolate mofetil, i.v. or oral cyclosporine A, or any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors, IL-2, anti-IL-6, anti-IL-17).
- •Previous treatment with any cell-depleting therapies, including but not limited to anti-CD20, unless ≥ 12 months prior to screening.
- •Any viral, bacterial or other infections at the time of screening or randomization, or history of recurrent clinically significant infection or of recurrent bacterial infection.
- •History of malignancy of any organ system (other than localized non melanoma carcinoma of the skin or in situ cervical cancer) within the last five years of randomization or any malignancy not in remission.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Part A- DDY391 dose level 1
DDY391 dose level 1
干预措施: DDY391 (Drug)
Part B- DDY391 dose level 1
DDY391 dose level 1
干预措施: DDY391 (Drug)
Part B- DDY391 dose level 2
DDY391 dose level 2
干预措施: DDY391 (Drug)
Part B- DDY391 dose level 3
DDY391 dose level 3
干预措施: DDY391 (Drug)
Part B- Placebo
Matching placebo. At the Week 24 visit, all participants will be randomized to DDY391 dose level 1 or dose level 2.
干预措施: Placebo (Drug)
Part C- DDY391 dose level 1
DDY391 dose level 1
干预措施: DDY391 (Drug)
Part C- Placebo
Matching placebo. At the Week 24 visit, all participants will be randomized to DDY391 dose level 1 or dose level 2.
干预措施: DDY391 (Drug)
Part C- Placebo
Matching placebo. At the Week 24 visit, all participants will be randomized to DDY391 dose level 1 or dose level 2.
干预措施: Placebo (Drug)
Part A-Placebo
Matching placebo. At the Week 24 visit, all participants will be randomized to DDY391 dose level 1 or dose level 2.
干预措施: DDY391 (Drug)
Part A-Placebo
Matching placebo. At the Week 24 visit, all participants will be randomized to DDY391 dose level 1 or dose level 2.
干预措施: Placebo (Drug)
Part B- Placebo
Matching placebo. At the Week 24 visit, all participants will be randomized to DDY391 dose level 1 or dose level 2.
干预措施: DDY391 (Drug)
结局指标
主要结局
Part A and B: Change from baseline in ESSDAI score
时间窗: Baseline, Week 24
EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) is a validated tool for assessing disease activity in SjD. Score range is 0-123. Higher scores on the ESSDAI scale are associated with poorer health states. A negative change from baseline indicates improvement in disease status.
Part C: Change from baseline in ESSPRI
时间窗: Baseline, Week 24
EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is a validated disease outcome measure for SjD. It consists of three domains of dryness, pain, and fatigue. The participant will assess severity of symptoms they experienced over the last 14 days on a single 0-10 numerical rating scale for each of the three domains. The ESSPRI score is defined as the mean of scores from the three scales: (dryness + pain + fatigue) /3. The total ESSPRI score ranges from 0 (no symptoms) to 10 (maximal symptom severity).
次要结局
- Part A and B: Change from baseline in ESSPRI(Baseline, Week 24)
- Part A, B and C: Change from baseline in SSSD(Baseline, Week 24)
- Part A, B and C: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 52)