An Adaptive Phase 2 Randomized Double-blind, Placebo-controlled Multi-center Study to Evaluate the Safety and Efficacy of Multiple LOU064 Doses in Patients With Moderate to Severe Sjögren's Syndrome (LOUiSSe)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score at Week 24
研究概览
简要总结
This was an adaptive design phase 2 study to establish safety and efficacy; and to characterize the dose-response of LOU064 in subjects with moderate to severe Sjögren's syndrome. LOU064 is an oral Bruton's tyrosine kinase (BTK) inhibitor.
详细描述
This study was planned as an adaptive Phase 2 randomized, double-blind, placebo-controlled, multi-center, integrated dose-ranging study to evaluate the safety and efficacy of multiple remibrutinib doses in patients with moderate to severe Sjögren's Syndrome.
Of the initially planned two parts, only Part 1 of the study was conducted. In Part 1, the highest expected biologically active single dose of remibrutinib (100 mg) was tested in two different dosing regimens, a once daily dose (qd) or twice daily dose (bid), and compared to the placebo group. Each patient in Part 1 of the study underwent a screening period of up to 6 weeks, a treatment period of 24 weeks, and a follow-up period of 30 days post-treatment before the End of Study (EOS) visit. The total duration for each patient in the study, including Screening, was up to 35 weeks. For the treatment period, patients were randomized in a 1:1:1 ratio to one of the 3 treatment groups: remibrutinib 100 mg bid, remibrutinib 100 mg qd and placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Diagnosis of SjS according to the 2016 ACR/EULAR criteria
- •Screening ESSDAI (based on weighted score) ≥ 5 derived from 8 domains
- •Screening ESSPRI ≥ 5
- •Seropositive for anti-Ro/SSA antibodies at or within 3 months prior to screening
- •Unstimulated salivary flow > 0 mL/min.
排除标准
- •Sjögren's Syndrome overlap syndromes with another autoimmune disease as primary illness
- •DMARDs or kinase inhibitors within 3 months prior to baseline above certain doses OR maintained during study
- •Rituximab or other B cell depleting drug within 12 months of Screening .
- •Current use of prednisone or equivalent > 15mg/d or dose change within 2 weeks prior to Screening
- •Use of medication known to cause, as a major side effect, dry mouth / eyes
- •HIV, Hepatitis C, Hepatitis B, known or suspected history of an ongoing, chronic or recurrent infectious disease such as tuberculosis
研究组 & 干预措施
Remibrutinib 100 mg bid
Remibrutinib 100 mg twice daily (bid)
干预措施: Remibrutinib (Drug)
Remibrutinib 100 mg qd
Remibrutinib 100 mg once daily (qd)
干预措施: Remibrutinib (Drug)
Remibrutinib 100 mg qd
Remibrutinib 100 mg once daily (qd)
干预措施: Placebo (Drug)
Placebo
Placebo group
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score at Week 24
时间窗: Baseline, Week 24
ESSDAI is a validated disease outcome measure for Sjögren's Syndrome. The instrument contains 12 organ-specific domains contributing to disease activity: constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, muscular, peripheral nervous system, central nervous system, hematological and biological. For each domain, features of disease activity were scored according to their severity. These scores were summed across the 12 domains in a weighted manner to provide the total score. ESSDAI total score ranges from 0 to 123 with higher values indicating more disease activity. A negative change from baseline indicates improvement. The baseline value is defined as the last assessment performed prior to administration of the first dose of study treatment. A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in ESSDAI for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
次要结局
- Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time(Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24)
- Change From Baseline in ESSDAI Total Score Over Time(Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20)
- Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time(Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24)
- Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time(Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24)
- Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 4(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time(Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs(From first dose of study treatment up 30 days after last dose (Week 29))
- Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 4(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4)
- Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 24(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24)
- Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 4(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4)
- Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 24(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24)
- Elimination Half-life (T1/2) of Remibrutinib at Week 24(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24)
- Elimination Half-life (T1/2) of Remibrutinib at Week 4(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4)
- Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 24(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24)
- Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 4(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4)
- Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 24(pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24)