A 14 Week Phase 2b, Randomized, Double-Blind, Dose-Ranging Study to Determine the Pharmacokinetics, Efficacy, Safety and Tolerability of TEV-48574 in Adult Patients With Ulcerative Colitis or Crohn's Disease (RELIEVE UCCD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 290
- 试验地点
- 164
- 主要终点
- Number of Participants With Moderate to Severe UC Who Showed Clinical Remission as Defined by the MMS
研究概览
简要总结
The primary objective is to characterize the efficacy TEV-48574 in adult participants with IBD (moderate to severe Ulcerative Colitis (UC) or Crohn's Disease (CD)) as assessed by induction of clinical remission (UC) and endoscopic response (CD) at week 14.
Secondary objectives:
- To evaluate the efficacy of 2 different doses of TEV-48574 as assessed by multiple standard measures
- To evaluate the safety and tolerability of 2 different doses of TEV-48574
- To evaluate the immunogenicity of 2 different dioses of TEV-48574
The study will consist of a screening period of up to 6 weeks (42 days), a 14-week treatment period, and a 4-week follow-up period.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Ulcerative Colitis (UC) or Crohn's Disease (CD) for ≥3 months
- •The participant is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study
- •The participant is able to understand the nature of the study and any potential hazards associated with participating in the study
- •Women of non-childbearing potential who are either surgically (documented hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or congenitally sterile as assessed by a physician, or 1-year postmenopausal
- •Male participants (including vasectomized) with women of childbearing potential (WOCBP) partners (whether pregnant or not) must use condoms after the first investigational medicinal product (IMP) administration and throughout the study or until 50 days after the last IMP dose, whichever is longer
- •NOTE- Additional criteria apply, please contact the investigator for more information
排除标准
- •The participant has any concomitant conditions or treatments that could interfere with study conduct, influence the interpretation of study observations/results, or put the participant at increased risk during the study as judged by the investigator and/or the clinical study physician
- •Diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic coliti
- •Participant has colonic dysplasia or neoplasia, toxic megacolon, primary sclerosing cholangitis, known non-passable colonic stricture, presence of colonic or small bowel stoma, presence of non-passable colonic or small bowel obstruction or resection preventing the endoscopy procedure, or fulminant colitis
- •Presence of active enteric infections (positive stool culture) or a history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks prior to the first screening visit
- •Participant anticipates requiring major surgery during this study.
- •A participant is Hepatitis B core antibody or surface antigen positive and/or Hepatitis C antibody positive with detectable ribonucleic acids, or positive human immunodeficiency virus types 1 or 2 at screening.
- •A history of an opportunistic infection (eg, cytomegalovirus retinitis, Pneumocystis carinii, or aspergillosis)
- •A history of more than 2 herpes zoster episode in the last 5 years or multimetameric herpes zoster
- •A history of or ongoing chronic or recurrent serious infectious disease (eg, infected indwelling prosthesis or osteomyelitis)
- •The participant is currently pregnant or lactating or is planning to become pregnant or to lactate during the study or for at least 50 days after administration of the last dose of IMP in case of early termination. Any woman becoming pregnant during the study will be withdrawn from the study.
- •Presence of a transplanted organ
- •A history of malignancy within the last 5 years (exception: basal cell carcinoma or in situ carcinoma of the cervix if successful curative therapy occurred at least 12 months prior to screening) or curatively resected papillary thyroid cance
- •Current or history (within 2 years) of serious psychiatric disease or alcohol or drug abuse
- •Participants with incurable diseases, persons in nursing homes, and participants incapable of giving written informed consent
- •NOTE- Additional criteria apply, please contact the investigator for more information
研究组 & 干预措施
TEV-48574, 1800 mg (CD)
Administered by subcutaneous infusion for participants with CD. This arm was discontinued with Amend 03.
干预措施: TEV-48574 (Drug)
Placebo UC
Matching Placebo
干预措施: Placebo (Drug)
Placebo CD
Matching Placebo
干预措施: Placebo (Drug)
TEV-48574, 450 mg (UC)
Administered by subcutaneous infusion for participants with UC
干预措施: TEV-48574 (Drug)
TEV-48574, 900 mg (UC)
Administered by subcutaneous infusion for participants with UC
干预措施: TEV-48574 (Drug)
TEV-48574, 1800 mg (UC)
Administered by subcutaneous infusion for participants with UC. This arm was discontinued with Amend 03.
干预措施: TEV-48574 (Drug)
TEV-48574, 450 mg (CD)
Administered by subcutaneous infusion for participants with CD
干预措施: TEV-48574 (Drug)
TEV-48574, 900 mg (CD)
Administered by subcutaneous infusion for participants with CD
干预措施: TEV-48574 (Drug)
结局指标
主要结局
Number of Participants With Moderate to Severe UC Who Showed Clinical Remission as Defined by the MMS
时间窗: Week 14
The MMS is a tool designed to measure disease activity for UC. It consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review. Each subscore was graded from 0 (normal) to 3 (severe). These individual subscores were summed up to give a total MMS ranging from 0 (normal or inactive disease) to 9 (severe disease), where higher scores indicated more severe disease activity. Clinical remission was defined as MMS ≤2 points with Mayo stool frequency subscore of 0 or 1, Mayo rectal bleeding subscore of 0, and centrally read endoscopic score of 0 or 1, where a score of 1 did not include "friability".
Number of Participants With Moderate to Severe CD Who Showed an Endoscopic Response as Defined by the SES-CD
时间窗: Baseline to Week 14
The SES-CD assessed the degree of inflammation. The SES-CD assesses the following 4 components: presence of ulcers, percentage of ulcerated surfaces, affected surface, and presence of strictures. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components was assessed in the 5 segments: the rectum, sigmoid and left colon, transverse colon, right colon, and ileum. The SES-CD was the sum of the individual scores of each of the components across the 5 segments. The range of SES-CD scores was 0 (none) - 12 (severe) for each segment, and 0 (none) - 60 (severe) for the overall SES-CD score, with larger scores indicating greater degree of inflammation. Endoscopic response at Week 14 in participants with moderate to severe CD was defined as a reduction in SES-CD of at least 50% from baseline.
次要结局
- Number of Participants With Moderate to Severe UC With a Clinical Response as Defined by the MMS(Baseline to Week 14)
- Number of Participants With Moderate to Severe UC With Endoscopic Improvement as Defined by the Mayo Endoscopic Subscore (MES)(Week 14)
- Number of Participants With Moderate to Severe UC With Endoscopic Remission as Defined by the MES(Week 14)
- Number of Participants With Moderate to Severe UC With a Clinical Response as Defined by 2-item Patient-reported Outcome (PRO2) Score(Baseline to Week 14)
- Number of Participants With Moderate to Severe UC With a Clinical Remission as Defined by PRO2 Score(Week 14)
- Number of Participants With Moderate to Severe CD With an Endoscopic Response as Defined by the Modified Multiplier-Simple Endoscopic Score (MM-SES-CD)(Baseline to Week 14)
- Number of Participants With Moderate to Severe CD With a Clinical Response as Defined by Crohn's Disease Activity Index (CDAI) Score(Baseline to Weeks 4, 8, 12 and 14)
- Number of Participants With Moderate to Severe CD With a Clinical Remission as Defined by CDAI Score(Week 14)
- Number of Participants With Moderate to Severe CD With a Clinical Response as Defined by PRO2-CD Score(Baseline to Week 14)
- Number of Participants With Moderate to Severe CD With a Clinical Remission as Defined by PRO2-CD Score(Week 14)
- Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)(Baseline (Day 1) up to Week 18)
- Number of Participants Who Stopped Taking the Investigational Medicinal Product (IMP) Due to AEs(Baseline (Day 1) up to Week 18)
- Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADAs)(Weeks 2, 4, 8, 14, and 18)
- Number of ADA Positive Participants With the Presence of Neutralizing ADA(Weeks 2, 4, 8, 14, and 18)