A Phase 2, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Efficacy and Safety study of SAR441566 plus Methotrexate in Adults with Moderate-to-Severe Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 240
- 试验地点
- 7
- 主要终点
- Response to ACR20 (proportion of participants
研究概览
简要总结
This is a parallel group, Phase 2, randomized, double-blind, placebo controlled, 5-arm, international, multicenter, 12-week proof of concept, dose finding study. It is designed to assess efficacy and safety of treatment with SAR441566 for 12 weeks. It will be conducted in male and female adult participants with moderate-to-severe RA not adequately controlled on MTX and biologic/targeted synthetic DMARD naive. Study treatment includes investigational medicinal product (IMP: SAR441566 or placebo) added-on to a background therapy of MTX. Study details include: • Run-in period (6 weeks ±3 days), with blood draw (2 weeks ±3 days) before randomization to determine eligibility. Treatment period (12 weeks ±3 days). • Post-treatment period (safety follow-up) (2 weeks ±3 days). • The total number of scheduled study visits will be 8. At least 6 weeks prior to screening, participants must be using a stable dose of MTX, between 10-25 mg (or per local labelling requirements for the treatment of RA if dose range differs). They must continue this stable dose during run-in and throughout the study. Participants who satisfy the inclusion and exclusion criteria will be randomized (2:2:1:1:2 ratio) to either SAR441566 (200 mg BID, 200 mg QD, 100 mg QD, 50 mg QD) or matching placebo, administered orally BID on top of MTX for 12 weeks. Visits during the 12-week treatment period will occur at week 0 (baseline/randomization), 2, 4, 8 and 12. Followed by a 2-week post-treatment period (safety follow-up).
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •At least 18 years old (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the informed consent.
- •Diagnosis of adult-onset RA classified by ACR/EULAR 2010 revised classification criteria for RA (28) of at least 3 months duration, with the onset of signs and symptoms of RA of at least 6 months duration.
- •Moderate-to-severely active RA, defined as: -- Persistently active disease more than equal to 6 tender and more than equal to 6 swollen joints. -- High sensitivity C-reactive protein more than 5 mg/L.
- •Participants who stopped biologic treatment due to non-response, partial response, loss of efficacy (e.g., failure to achieve or maintain remission (IGA 0, clear skin to 2, mild disease)) must have been previously treated with biologic (at labelled dose level) for at least 4 months, as confirmed by investigator judgment.
- •Continuous treatment with MTX for at least 12 consecutive weeks prior to randomization and with stable dose/means of administration at least 6 weeks prior to the screening visit. --MTX – 10 to 25 mg/week (or per local labeling requirements for the treatment of RA if the dose range differs, eg, for Japan, a stable dose of MTX is 6 to 16 mg/week) and folic/folinic acid (as part of MTX regimen).
- •BMI within the range (
- •kg/m2 (inclusive).
- •All contraceptive methods used by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- •Male participants Male participants are eligible to participate if they agree to the following during the study treatment period and for at least 3 months after the last administration of study IMP:.
- •Refrain from donating or cryopreserving sperm; PLUS, either:.
- •Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; OR.
- •Must agree to use contraception as detailed below: A male condom and an additional highly effective contraceptive method (as described in Section 10.4), when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
- •Female participants A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:- Is a woman of nonchildbearing potential (WONCBP) as defined in the protocol; OR.
- •Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective (with a failure rate of less than 1percent per year), preferably with low user dependency (as described in Section 10.4) during the study intervention period (to be effective before starting the intervention) and for at least 3 months after the last administration of study intervention and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations%2.
排除标准
- •Immunologic disorder other than RA, with the exception of secondary Sjogrens syndrome associated with RA, and medically controlled diabetes or thyroid disorder as per Investigators judgement.
- •Any condition requiring oral, intravenous, IM, or intra-articular glucocorticoid therapy.
- •Uncontrolled polymyalgia rheumatica or fibromyalgia
- •History of recurrent or recent serious infection (eg, pneumonia, septicemia) or infection(s) requiring hospitalization or treatment with IV anti-infectives (antibiotics, antivirals, antifungals, antihelminthics) within 30 days prior to D
- •Infections(s) requiring oral antiinfectives (antibiotics, antivirals, antifungals, antihelminthics) within 14 days prior to D1
- •Known history of or suspected significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration
- •History of moderate-to-severe congestive heart failure (NYHA Class III or IV), recent cerebrovascular accident, or any other condition in the opinion of the Investigator that would put the participant at risk by participation in the protocol.
- •History of solid organ transplant.
结局指标
主要结局
Response to ACR20 (proportion of participants
时间窗: at Week 12
achieving at least 20% improvement from baseline
时间窗: at Week 12
in the ACR score) at Week 12
时间窗: at Week 12
次要结局
- - To assess the efficacy of SAR441566, with respect to placebo, plus MTX, on change from baseline to week 12 in DAS28-CRP and response to ACR50 in the treatment of RA(- To evaluate the safety and tolerability of SAR441566)