A Multicenter, Randomized, Double-Blind, Placebo Controlled 52-Week Maintenance and an Open-Label Extension Study of the Efficacy and Safety of Risankizumab in Subjects With Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,336
- 试验地点
- 830
- 主要终点
- Sub-Study 1: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission
研究概览
简要总结
The study consists of 4 sub-studies, as follows:
- Sub-study 1 (Randomized, double-blind, placebo controlled study) to evaluate the efficacy and safety of risankizumab versus placebo as maintenance therapy in participants with moderately to severely active Crohn's disease (CD) who responded to intravenous risankizumab induction treatment in Study M16-006 or Study M15-991;
- Sub-study 2 (Randomized, exploratory maintenance study) to evaluate the efficacy and safety of two different dosing regimens for risankizumab as maintenance therapy in participants who responded to induction treatment in Study M16-006 or Study M15-991;
- Sub-study 3 (Open-label, long-term extension study) to evaluate long-term safety of risankizumab in participants who completed Sub-study 1, Sub-study 2, another AbbVie risankizumab Crohn's disease study, or participants who responded to induction treatment in Study M16-006 or Study M15-991 with no final endoscopy due to the Covid-19 pandemic. Additional objectives are to further investigate long-term efficacy and tolerability of risankizumab;
- Sub-study 4 (Open-label On Body Injector (OBI) administration and long-term extension study) to evaluate patient-reported outcomes, efficacy, safety, tolerability, and pharmacokinetics of risankizumab administered via OBI in participants who are receiving maintenance treatment with risankizumab.
- OL CTE to ensure uninterrupted care in accordance with local regulations until risankizumab is commercially available for participants who completed Sub-study 3, Sub-study 4.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who have entered and completed Study M16-006 or Study M15-991 or other AbbVie risankizumab Crohn's disease study.
- •Participants have completed the study M16-006 or M15-991 and have achieved clinical response.
- •Sub-Study 4:
- •Participants receiving maintenance treatment in Sub-study 3 and willing to comply with the requirements of Sub-study 4, including self-administration of sub-cutaneous injections using the on-body injector (OBI).
- •Participant has received at least 16 weeks of stable dosing with risankizumab in Sub-study 3 (i.e., no rescue within 16 weeks and participant has surpassed the 72-week mark).
排除标准
- •Participants should not be enrolled in Study M16-000 with high grade colonic dysplasia or colon cancer identified during Study M15-991, Study M16-006 or another AbbVie risankizumab Crohn's disease study if the final endoscopy was performed prior to enter Study M16-000 OR is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
- •Participant who has a known hypersensitivity to risankizumab or the excipients of any of the study drugs or the ingredients of Chinese hamster ovary (CHO), OR had an adverse event (AE) during Studies M16-006, M15-991 or another AbbVie risankizumab Crohn's disease study that in the Investigator's judgment makes the participant unsuitable for this study.
- •Participant is not in compliance with prior and concomitant medication requirements throughout Studies M16-006, M15-991 or another AbbVie risankizumab Crohn's disease study.
- •Confirmed positive urine pregnancy test at the Final Visit of Study M16-006, Study M15-991 or another AbbVie risankizumab Crohn's disease study.
- •Have a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
- •Any active or chronic recurring infections based on the Investigator's assessment makes the participant an unsuitable candidate for the study.
研究组 & 干预措施
Maintenance Risankizumab Dose 1 (Sub-Study 2)
Participants will receive double-blind subcutaneous (SC)risankizumab dose 1 and intravenous placebo at Week 0 followed by open-label SC risankizumab dose 1 from Week 8 through Week 52.
干预措施: Placebo for Risankizumab IV (Drug)
Maintenance Risankizumab Dose 2 (Sub-Study 2)
Participants will receive double-blind subcutaneous placebo and intravenous risankizumab dose 3 at Week 0 followed by open-label SC risankizumab dose 1 from Week 8 through Week 52.
干预措施: Placebo for Risankizumab SC (Drug)
Double-blind Risankizumab Dose 1 (Sub-Study 1)
Participants randomized to receive double-blind risankizumab dose 1 for 52 weeks.
干预措施: Risankizumab SC (Drug)
Risankizumab On-Body Injector and Open Label (Sub-Study 4)
Participants in Sub-study 3 who meet eligible criteria for Sub-study 4 will receive risankizumab dose 1 or dose 2 via on-body injectors on Weeks 0,8 and 16. Beginning Week 24, participants will receive risankizumab dose 1 or dose 2 via pre-filled syringes Q8W.
干预措施: Risankizumab SC (Drug)
Maintenance Risankizumab Dose 2 (Sub-Study 2)
Participants will receive double-blind subcutaneous placebo and intravenous risankizumab dose 3 at Week 0 followed by open-label SC risankizumab dose 1 from Week 8 through Week 52.
干预措施: Risankizumab SC (Drug)
Risankizumab On-Body Injector and Open Label (Sub-Study 4)
Participants in Sub-study 3 who meet eligible criteria for Sub-study 4 will receive risankizumab dose 1 or dose 2 via on-body injectors on Weeks 0,8 and 16. Beginning Week 24, participants will receive risankizumab dose 1 or dose 2 via pre-filled syringes Q8W.
干预措施: Risankizumab On-Body Injector (OBI) (Drug)
Maintenance Risankizumab Dose 1 (Sub-Study 2)
Participants will receive double-blind subcutaneous (SC)risankizumab dose 1 and intravenous placebo at Week 0 followed by open-label SC risankizumab dose 1 from Week 8 through Week 52.
干预措施: Risankizumab SC (Drug)
CTE: Open Label Continuous Treatment Extension
Participants who tolerate and derive benefit from receiving risankizumab and complete Sub-study 3 or Sub-study 4 will receive risankizumab dose 1 or dose 2 Q8W.
干预措施: Risankizumab SC (Drug)
Double-blind Risankizumab Dose 2 (Sub-Study 1)
Participants randomized to receive double-blind risankizumab dose 2 for 52 weeks.
干预措施: Risankizumab SC (Drug)
Double-blind Placebo for Risankizumab (Sub-Study 1)
Participants randomized to receive double-blind placebo for risankizumab for 52 weeks.
干预措施: Placebo for Risankizumab SC (Drug)
Maintenance Risankizumab Dose 2 (Sub-Study 2)
Participants will receive double-blind subcutaneous placebo and intravenous risankizumab dose 3 at Week 0 followed by open-label SC risankizumab dose 1 from Week 8 through Week 52.
干预措施: Risankizumab IV (Drug)
Open-label Risankizumab (Sub-Study 3)
Participants who completed Sub-study 1 or Sub-study 2 or other AbbVie risankizumab Crohn's disease study or M16-006 or M15-991 without endoscopy will receive open-label risankizumab dose 1 or dose 2 depending on their preceding study beginning at Week 56.
干预措施: Risankizumab SC (Drug)
结局指标
主要结局
Sub-Study 1: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission
时间窗: Week 52
The CDAI is used to evaluate disease activity in patients with Crohn's disease. The CDAI clinical remission is defined as a CDAI score of \< 150.
Sub-Study 1: Percentage of Participants With Endoscopic Response
时间窗: Week 52
Endoscopic response defined as decrease from Baseline of the induction study in Simple Endoscopic Score for Crohn's Disease (SES-CD).
Sub-Study 3: Number of Participants With Adverse Events
时间窗: Up to Week 220
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent AEs are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.
Sub-Study 4: Percentage of Participants With an Observer Rating of Successful Participant Self Administration
时间窗: Up to Week 16
Participant who successfully completed the sequence of critical steps in the instructions for use (IFU) without errors to administer study drug via the OBI at Week 0 and 16.
Sub-Study 4: Percentage of Participants who had no Potential Hazards
时间窗: Up to Week 16
Measured by an observer on the possible use-related hazards checklist for self-administration with OBI at Week 0 and Week 16.
Sub-Study 4: Percentage of Participants Rating of Acceptability Using Self-Injection Assessment Questionnaire (SIAQ) at Weeks 0, 8, 16
时间窗: Up to Week 16
SIAQ evaluations consist of the PRE module, which is self-completed immediately before the first OBI self-injection at baseline, and the POST module, which is self-completed 20 to 40 min following injections at Weeks 0, 8, 16. These modules are completed by participants while alone in a quiet environment. Participants rate each item of the SIAQ. The ratings are later transformed to scores ranging from 0 (worst experience) to 10 (best experience). The domain score is the mean of the item scores included in the domain. Domain scores are calculated only if at least half of the domain items are completed. Item and domain scores from the PRE module are compared with the corresponding item and domain scores from the POST modules.
Sub-Study 4: Percentage of Participants in CDAI Clinical Remission at Week 0, 16
时间窗: Up to Week 16
Clinical remission per average daily stool frequency (SF) and average daily abdominal pain (AP) score.
次要结局
- Sub-Study 1: Percentage of Participants With Clinical Remission(Week 52)
- Sub-Study 1: Percentage of Participants With CDAI Clinical Remission Among Participants With CDAI Clinical Remission in Week 0(Week 52)
- Sub-Study 1: Percentage of Participants With Ulcer-Free Endoscopy(Week 52)
- Sub-Study 1: Percentage of Participants With Endoscopic Remission(Week 52)
- Sub-Study 1: Change From Baseline of Induction in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)(Week 52)
- Sub-Study 1: Percentage of Participants Who Discontinued Corticosteroid Use for 90 Days and Achieved Clinical Remission in Participants Taking Steroids at Baseline(Week 52)
- Sub-Study 1: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response(Week 52)
- Sub-Study 1: Percentage of Participants With Stool Frequency (SF) Remission(Week 52)
- Sub-Study 1: Percentage of Participants With Abdominal Pain (AP) Remission(Week 52)
- Sub-Study 1: Percentage of Participants With CDAI Clinical Remission and Endoscopic Response(Week 52)
- Sub-Study 1: Percentage of Participants With Deep Remission(Week 52)
- Sub-Study 1: Percentage of Participants With Exposure Adjusted Occurrence of CD-related Hospitalizations From Week 0 Through Week 52(Up to Week 52)