A Multicenter, Open-Label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,106
- 试验地点
- 234
- 主要终点
- Incidence Rate of Treatment Emergent AESIs (Safety Population)
研究概览
简要总结
The primary objective of this study was to evaluate the long-term safety and tolerability of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) in subjects with moderately to severely active rheumatoid arthritis (RA) who previously had completed 24 weeks of double-blind treatment in Study CREDO 1, 2 or 3 (core studies). The long-term efficacy, immunogenicity, the physical function and quality of life of subjects received long-term treatment with OKZ were assessed as well.
详细描述
This OLE study (CL04041024) included an 82-week open-label Treatment Period that followed completion of one of the core studies (Study CREDO 1, 2 or 3). The OLE open-label Treatment Period lasted from Visit 1 (OLE Baseline/Week 24) to Visit 10 (End of Treatment (EoT)/Week 106), followed by a 20-week Safety Follow-Up Period from Week 106 to Week 126. The first visit of the OLE study was the same visit as the Week 24 visit in the core studies.
Subjects were randomized to 1 of the 2 OKZ treatment groups in the OLE study based on the treatment received in the core studies. Subjects who had received OKZ (q2w or q4w) in the core study in which they had participated (including subjects who received placebo in Study CREDO 3 and were re-randomized to OKZ at Week 16) received the same OKZ treatment regimen in the OLE study. Subjects who had received placebo (Study CREDO 1 and CREDO 2) or adalimumab (Study CREDO 2) in the core study in which they had participated were randomized in a 1:1 ratio to OKZ 64 mg q2w or OKZ 64 mg q4w regimens in the OLE study.
For the first 12 weeks of the OLE, all subjects were required to remain on a stable dose of background methotrexate (MTX) at 15 to 25 mg/week (or≥10 mg/week if there was documented intolerance to higher doses) with a stable route of administration (oral, SC, or intramuscular (IM)). After 12 weeks (Visit 4 [Week 36] of the OLE study), the Investigator might adjust the MTX dosage and route, per local guidelines. Methotrexate might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study.
Subjects who had been on rescue disease-modifying anti-rheumatic drugs (DMARDs) during the core studies were asked to continue these medications for the first 12 weeks of the OLE study. The Investigator could adjust these background medications if deemed appropriate after Visit 4 (Week 36) of the OLE study. Background rescue therapy might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study.
Throughout the study, concomitant treatment with folic acid ≥ 5 mg per week or equivalent was required for all subjects.
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
- None
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
- •Subjects may be enrolled in the study only if they meet all of the following criteria:
- •Subject must be willing and able to sign informed consent
- •Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025).
- •Subject must have maintained their stable dose (and route) of MTX 15 to 25 mg/week (or ≥ 10 mg/week if there is documented intolerance to higher doses) during the core study and plan to maintain the same dose and route of administration for ≥ 12 additional weeks
- •Subjects must be willing to take folic acid or equivalent throughout the study.
排除标准
- •Subject with any medically important condition in the core study (e.g., clinically significant laboratory values, frequent Adverse events (AEs) or serious adverse events (SAEs), infection SAEs, and/or other concurrent severe and/or uncontrolled medical condition) which would make this subject unsuitable for inclusion in the open-label extension (OLE) study in the Investigator's judgement.
- •Subject has evidence of active tuberculosis (TB)
- •Subject with a positive or repeated indeterminate interferon-gamma release assay (IGRA) result at Week 22 of the core study
- •Subjects may be enrolled in the OLE study if they fulfill all 3 of the following criteria prior to the first dose of study treatment:
- •Active TB is ruled out by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice);
- •The subject starts prophylaxis for latent TB infection (LTBI) according to country-specific/Centers for Disease Control and Prevention (CDC) guidelines (treatment with isoniazid for 6 months is not an appropriate prophylactic regime for this study and it should not be used); and
- •The subject is willing to complete the entire course of recommended LTBI therapy.
- •Subject has planned surgery during the first 12 weeks of the OLE study
- •Female subjects who are pregnant or who are planning to become pregnant during the study or within 6 months of the last dose of study drug
- •Female subjects of childbearing potential (unless permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of natural amenorrhea as defined by the amenorrhea with underlying status [e.g., correlative age] or 6 months of natural amenorrhea with documented serum follicle-stimulating hormone levels >40 mIU/mL and estradiol <20 pg/mL) who are not willing to use a highly effective method of contraception during the study and for at least 6 months after the last administration of study treatment OR Male subjects with partners of childbearing potential not willing to use a highly effective method of contraception during the study and for at least 3 months after the last administration of study treatment.
- •Highly effective contraception is defined as:
- •Female sterilization surgery: hysterectomy, surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to the first dose of study treatment in the core study
- •In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by documented follow-up hormone level assessment
- •Total abstinence if it is the preferred and constant lifestyle of the subject. Thus, periodic abstinence such as ovulation, symptothermal, postovulation, calendar methods, and withdrawal are not acceptable methods of contraception.
- •Male sterilization surgery: at least 6 months prior to the first dose of study treatment in the core study (with the appropriate postvasectomy documentation of the absence of sperm in the ejaculate). For female subjects, the vasectomized male should be the only partner.
- •Placement of established intrauterine device (IUD): IUD copper or IUD with progesterone
- •Barrier method (condom and intravaginal spermicide, cervical caps with spermicide, or diaphragm with spermicide) in combination with the following: established oral, injected, or implanted hormone methods of contraception or contraceptive patch.
- •Subject is unwilling or unable to follow the procedures outlined in the protocol.
- •Other medical or psychiatric conditions, or laboratory abnormalities that may increase the potential risk associated with study participation and administration of the study treatment, or that may affect study results interpretation and, as per Investigator's judgement, make the subject ineligible.
研究组 & 干预措施
Treatment Arm 1: OKZ 64 mg q4w + MTX
Olokizumab 64 mg SC q4w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
干预措施: Olokizumab 64 mg SC q4w (Drug)
Treatment Arm 1: OKZ 64 mg q4w + MTX
Olokizumab 64 mg SC q4w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
干预措施: Concomitant treatment (Drug)
Treatment Arm 2: OKZ 64 mg q2w + MTX
Olokizumab 64 mg SC q2w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
干预措施: Olokizumab 64 mg SC q2w (Drug)
Treatment Arm 2: OKZ 64 mg q2w + MTX
Olokizumab 64 mg SC q2w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
干预措施: Concomitant treatment (Drug)
结局指标
主要结局
Incidence Rate of Treatment Emergent AESIs (Safety Population)
时间窗: up to Week 126
Incidence Rate of all Subjects with at Least One Treatment Emergent AESI. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population)
时间窗: up to Week 126
Incidence of Serious Treatment-Emergent Adverse Events by System Organ Class or Preferred Term. Deaths are included.
Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment
时间窗: up to Week 126
Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI)
时间窗: up to Week 126
Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population)
时间窗: up to Week 126
Incidence of Treatment-Emergent Adverse Events Reported for ≥5% of Subjects in Any Treatment Group by System Organ Class or Preferred Term
Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure
时间窗: up to Week 126
Incidence Rate of all Subjects with at Least One Treatment Emergent AE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure
时间窗: up to Week 126
Incidence Rate of all Subjects with at Least One Treatment Emergent SAE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
次要结局
- American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82(up to Week 82)
- Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40(Core baseline, Week 40)
- Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12(Core baseline, Week 12)
- Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28(Core baseline, Week 28)
- Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52(Core baseline, Week 52)
- American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82(up to Week 82)
- Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82(up to week 82)
- Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20(Core baseline, Week 20)
- American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82(up to Week 82)
- Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82(up to Week 82)
- Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82(Core baseline, Week 82)
- Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82(up to week 82)
- Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64(Core baseline, Week 64)
- Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI)(up to week 82)