A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase II Study to Evaluate The Safety and Efficacy of RO7123520 as Adjunct Treatment in Patients With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to TNF-alpha Inhibitors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 109
- 试验地点
- 80
- 主要终点
- Percentage of Participants With Adverse Events
研究概览
简要总结
This is a Phase IIa/b double-blind, placebo-controlled, randomized, parallel group, multicenter study to evaluate the safety and efficacy of RO7123520 as adjunctive therapy in participants with RA who are inadequately responding to standard-of-care (methotrexate and anti-TNF-alpha therapy). Part 1 of the study will evaluate safety. Part 2 will evaluate efficacy and safety. Part 3 will evaluate dose-ranging efficacy. Participants will have the option of continuing to the extension period of the study.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of adult-onset RA as defined by the ACR 2010 criteria, for at least 6 months before screening
- •Moderately to severely active RA as defined by at least 4/28 tender joints and at least 4/28 swollen joints, and a DAS28 greater than or equal to (≥) 3.2
- •For Part 2 only: Active synovitis and/or osteitis as determined by contrast-enhanced magnetic resonance imaging
- •Participants must be taking stable dose of anti-TNF-alpha therapies
- •Participants on stable oral glucocorticoids within 6 weeks of planned randomization
- •Participants taking non-steroidal anti-inflammatory drugs (NSAIDs) intermittently (up to 2-3 times weekly) for short-term relief of pain and participants on regular NSAID use (on stable dose for ≥ 4 weeks)
排除标准
- •Parenteral glucocorticoids administration (intramuscular, IV) of ≥50 mg within 6 weeks or less than or equal to (≤) 50 milligrams (mg) within 4 weeks prior to planned randomization, or scheduled parenteral administrations during the study
- •Joint(s) injected with intra-articular glucocorticoids or hyaluronic acid within 6 weeks prior to planned randomization
- •Active inflammatory diseases of the joints not related to RA
- •Systemic autoimmune disease other than RA
- •Juvenile idiopathic arthritis or juvenile RA and/or RA developed before the age of 16
- •Active fibromyalgia that makes appropriate assessment of RA disease activity challenging in the opinion of the Investigator
- •RA participants functional status class IV according to the ACR 1991 criteria
- •Participants with severe chronic or recurrent viral, bacterial, parasitic, or fungal infections
- •History of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
- •Any identified confirmed congenital or acquired immunodeficiency
- •Abnormal laboratory values and liver function test
- •Myocardial infarction within less than 6 months prior to participation in the study
- •Severe central or peripheral nervous system diseases
研究组 & 干预措施
Part 1: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Anti-TNF-alpha (Drug)
Part 1: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Methotrexate (Drug)
Part 1: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Placebo (Drug)
Part 1: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Anti-TNF-alpha (Drug)
Part 1: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Methotrexate (Drug)
Part 1: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: RO7123520 (Drug)
Part 2: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Anti-TNF-alpha (Drug)
Part 2: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Methotrexate (Drug)
Part 2: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Placebo (Drug)
Part 2: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Anti-TNF-alpha (Drug)
Part 2: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: Methotrexate (Drug)
Part 2: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
干预措施: RO7123520 (Drug)
Part 3: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
NOTE: Part 3 was not conducted.
干预措施: Anti-TNF-alpha (Drug)
Part 3: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
NOTE: Part 3 was not conducted.
干预措施: Methotrexate (Drug)
Part 3: Placebo
Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
NOTE: Part 3 was not conducted.
干预措施: Placebo (Drug)
Part 3: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
NOTE: Part 3 was not conducted.
干预措施: Anti-TNF-alpha (Drug)
Part 3: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
NOTE: Part 3 was not conducted.
干预措施: Methotrexate (Drug)
Part 3: RO7123520
Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
NOTE: Part 3 was not conducted.
干预措施: RO7123520 (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events
时间窗: Baseline to last participant last visit (approximately 2 years)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12
时间窗: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[most often Health Assessment Questionnaire (HAQ)\], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.
Percentage of Participants With Anti-Drug Antibodies
时间窗: Baseline
Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans
时间窗: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
次要结局
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12(Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24))
- Change From Baseline in Disease Activity Score 28 (DAS28) at Week 12(Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24))
- Percentage of Participants Achieving DAS28 Remission at Week 12(Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24))
- Percentage of Participants Achieving CDAI Remission at Week 12(Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24))
- Percentage of Participants Achieving ACR20 Response at Week 12(Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24))
- Percentage of Participants Achieving ACR70 Response at Week 12(Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24))
- Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 12(Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24))
- Change From Baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12(Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24))
- Serum RO7123520 Concentration(Pre-dose (0 hour), 1 hour post infusion (duration of infusion: approximately 1 hour) on Days 1, 14, 28, 56; Pre-dose (0 hour) on Days 84, 112)
- Synovial Fluid RO7123520 Concentration(Pre-dose (0 hour) on Days 1, 84)