A Randomized, Double-Blind, Placebo-Controlled, 2-Part Phase 2 Study to Evaluate the Safety and Efficacy of LY3337641 in Adult Subjects With Rheumatoid Arthritis: The RAjuvenate Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 286
- 试验地点
- 19
- 主要终点
- Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) or Adverse Events of Special Interest (AESIs) or Any Serious AEs (SAEs) in Part A
研究概览
简要总结
The main purpose of this study is to evaluate the safety and effectiveness of LY3337641 in adults with rheumatoid arthritis (RA).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female subjects of childbearing potential test negative for pregnancy at screening and agree not to breastfeed
- •Female subjects: agree to use a reliable method of birth control from the start of screening until 28 days after the last dose of study drug or be of nonchildbearing potential
- •Male subjects: agree to use a reliable method of birth control from the start of screening until 2 weeks after the last dose of study drug or have undergone vasectomy
- •Have a diagnosis of RA based on the 2010 American College of Rheumatology (ACR)/European League against Rheumatism criteria
- •Have at least 1 of the following:
- •rheumatoid factor or anti-citrullinated peptide antibodies (ACPA) at screening OR
- •radiographs documenting bony erosions
- •Have active RA, defined as:
- •Part A: ≥3 swollen joints (based on 66-joint counts)
- •≥6 swollen joints (based on 66-joint counts)
- •≥6 tender joints (based on 68-joint counts)
- •hsCRP levels greater than the upper limit of normal (ULN) OR positive for ACPA
- •Part B only: Have had inadequate response, loss of response, or intolerance to at least 1 synthetic OR biologic disease-modifying antirheumatic drug (DMARD)
排除标准
- •Have received any of the following:
- •Part B only: any prior treatment with a product directly targeting Bruton's tyrosine kinase (BTK) (marketed or investigational)
- •belimumab, natalizumab, or vedolizumab within 6 months prior to baseline
- •B-cell-depleting agents (such as rituximab) or other cell-depleting biologics (eg, anti-cluster of differentiation 3 (CD3) antibody) within 12 months prior to screening for Part A or at any time prior to screening for Part B
- •Have known hypogammaglobulinemia
- •Have hepatitis C virus, hepatitis B virus or human immunodeficiency virus
- •Have active tuberculosis (TB)
- •Are at high risk of infection or have recent evidence of clinically significant infection
- •Have had lymphoma, leukemia, or any malignancy within the previous 5 years except for treated basal cell or squamous epithelial carcinomas of the skin
- •Have received a live (attenuated) vaccine within 28 days prior to baseline or plan to receive one during the study
研究组 & 干预措施
Part B 10 mg LY3337641
Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.
干预措施: LY3337641 (Drug)
Part A 5 mg LY3337641
Given once a day for 4 weeks.
干预措施: LY3337641 (Drug)
Part A 10 mg LY3337641
Given once a day for 4 weeks.
干预措施: LY3337641 (Drug)
Part A 30 mg LY3337641
Given once a day for 4 weeks.
干预措施: LY3337641 (Drug)
Part A Placebo
Given once a day for 4 weeks.
干预措施: Placebo (Drug)
Part B 5 mg LY3337641
Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.
干预措施: LY3337641 (Drug)
Part B 30 mg LY3337641
Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.
干预措施: LY3337641 (Drug)
Part B Placebo
Given once a day for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) or Adverse Events of Special Interest (AESIs) or Any Serious AEs (SAEs) in Part A
时间窗: Up to 6 Weeks
TEAEs are any untoward medical occurrence that either occurs or worsens at any time after treatment baseline, and in the opinion of the investigators is possibly related to study drug. Skin Rash was the only event that was considered an AESI. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of SAEs and other non-serious AEs, regardless of whether or not they were possibly related to study drug, is located in the Reported Adverse Event section.
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response in Part B
时间窗: Week 12
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using visual analog scale (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI) and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and /or participants who discontinue study or drug before analysis timepoint are deemed non-responders.
次要结局
- Pharmacokinetics (PK): Clearance Parameter of LY3337641(Part A: Weeks 1, 2, and 4, Day 1 (0.5 to 2 hours postdose); Part B: Weeks 2, 4, 8, and 12, Day 1 (0.5 to 2 hours postdose))
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response in Part B(Week 12)
- Percentage of Participants Who Achieve Clinical Remission Using DAS28-hsCRP in Part B(Week 12)
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response in Part B(Week 12)
- Percentage of Participants Who Achieve Low Disease Activity Using DAS28-hsCRP in Part B(Week 12)
- Change From Baseline in the Disease Activity Score (DAS) 28-high-sensitivity C-reactive Protein (hsCRP) in Part B(Baseline, Week 12)