A Phase 3, Randomized, Double-Blind, Placebo-Controlled Program to Evaluate the Efficacy and Safety of MK-7240 in Participants With Moderately to Severely Active Ulcerative Colitis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,020
- 试验地点
- 949
- 主要终点
- Study 1: Percentage of Participants Achieving Clinical Remission Per Modified Mayo Score (MMS) at Week 12
研究概览
简要总结
The purpose of this protocol is to evaluate the efficacy of tulisokibart in participants with moderately to severely active ulcerative colitis. Study 1's primary hypotheses are that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission according to the Modified Mayo Score at Week 12, and that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission according to the Modified Mayo Score at week 52. Study 2's primary hypothesis is that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission according to the Modified Mayo Score at Week 12.
详细描述
The protocol consists of 2 studies. Study 1 includes induction and maintenance treatment, and Study 2 includes only induction treatment. Each study has its own hypotheses and outcome measures that will be assessed independently.
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)
盲法说明
Induction and maintenance treatments will be blinded. Reinduction will not be blinded.
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
- •Has had ulcerative colitis (UC) (from onset of symptoms) for at least 3 months before randomization
- •Has moderately to severely active UC
- •Weight ≥40 kg
- •Satisfies at least 1 of the following criteria:
- •Has had an inadequate response or loss of response to 1 or more protocol-specified UC treatments
- •Protocol specified corticosteroid dependence
- •Has been intolerant to 1 or more protocol-specified UC treatments
- •Is on treatment with any protocol-specified drugs during the study and meets drug stabilization requirements, as applicable
- •Adolescent participants ≥16 and <18 years of age can participate if approved by the country or regulatory/health authority
- •A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding and Is not a participant of childbearing potential (POCBP); or is a POCBP and uses an acceptable contraceptive method, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention, medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy
排除标准
- •Has a diagnosis of Crohn's Disease (CD) or indeterminate colitis (inflammatory bowel disease (IBD)-undefined) or other types of colitis or enteritis that may confound efficacy assessment.
- •Has a current diagnosis of fulminant colitis and/or toxic megacolon
- •Has UC limited to the rectum (i.e, must have evidence of UC extending beyond the rectosigmoid junction, which is ~10 cm from the anal margin)
- •Has a current or impending need for colostomy or ileostomy
- •Has had a total proctocolectomy or partial colectomy
- •Has received fecal microbial transplantation within 4 weeks before randomization
- •Has had UC exacerbation requiring hospitalization within 2 weeks before screening
- •Has prior or current evidence of definite colonic dysplasia except for low-grade dysplasia that has been completely removed
- •Has any active or serious infections without resolution after adequate treatment
- •Has had cytomegalovirus infection that resolved less than 4 weeks before screening
- •Has a transplanted organ which requires continued immunosuppression
- •Has a history of cancer (except fully treated non-melanoma skin cell cancers or cervical carcinoma in situ after complete surgical removal) within the last 5 years
- •Is known to be infected with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
- •Has evidence of active tuberculosis (TB), latent TB not successfully treated (per local guidelines), or inadequately treated TB (for participants with history of TB)
- •Has confirmed or suspected COVID-19
- •Has a history of drug or alcohol abuse within 6 months prior to screening
- •Has had major surgery within 3 months before screening or has a major surgery planned during the study
- •Is currently receiving or is planning to receive total parenteral nutrition at any time during study treatment
- •Has received UC-related antibiotics and has not been on stable doses for at least 14 days before randomization or has discontinued these medications within 14 days of randomization
- •Requires treatment with a therapy that does not adhere to the protocol-specified guidance parameters
- •Has received protocol-specified prohibited medications
- •Has had prior exposure to tulisokibart or another anti-tumor necrosis factor-like cytokine 1A (TL1A) antibody
研究组 & 干预措施
Study 1: High Dose Induction, Low Dose Maintenance
Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: SC Tulisokibart (Drug)
Study 1: High Dose Induction, High Dose Maintenance
Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen.
干预措施: IV Tulisokibart (Drug)
Study 1: High Dose Induction, High Dose Maintenance
Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen.
干预措施: SC Tulisokibart (Drug)
Study 1: High Dose Induction, Low Dose Maintenance
Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: IV Tulisokibart (Drug)
Study 1: High Dose Induction, Low Dose Maintenance
Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: SC Placebo (Drug)
Study 1: Low Dose Induction, Low Dose Maintenance
Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: IV Tulisokibart (Drug)
Study 2: Placebo
Participants receive IV placebo.
干预措施: IV Placebo (Drug)
Study 1: Low Dose Induction, Low Dose Maintenance
Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: SC Tulisokibart (Drug)
Study 1: Low Dose Induction, Low Dose Maintenance
Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: SC Placebo (Drug)
Study 1: Placebo
Participants receive IV placebo, followed by an SC placebo regimen.
干预措施: IV Tulisokibart (Drug)
Study 1: Placebo
Participants receive IV placebo, followed by an SC placebo regimen.
干预措施: IV Placebo (Drug)
Study 1: Placebo
Participants receive IV placebo, followed by an SC placebo regimen.
干预措施: SC Placebo (Drug)
Study 1: High Dose Extension
Participants receive a high dose SC tulisokibart regimen. Participants may be enrolled in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Tulisokibart (Drug)
Study 1: Low Dose Extension
Participants receive a low dose SC tulisokibart and placebo regimen. Participants may be enrolled in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Tulisokibart (Drug)
Study 1: Low Dose Extension
Participants receive a low dose SC tulisokibart and placebo regimen. Participants may be enrolled in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Placebo (Drug)
Study 2: High Dose Induction
Participants receive high dose IV tulisokibart.
干预措施: IV Tulisokibart (Drug)
Study 2: Low Dose Induction
Participants receive low dose IV tulisokibart.
干预措施: IV Tulisokibart (Drug)
Study 2: Placebo
Participants receive IV placebo.
干预措施: IV Tulisokibart (Drug)
Study 2: Placebo
Participants receive IV placebo.
干预措施: SC Placebo (Drug)
Study 2: High Dose Extension
Participants receive a high dose SC tulisokibart regimen. Participants may be enrolled in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Tulisokibart (Drug)
Study 2: Low Dose Extension
Participants receive a low dose SC tulisokibart regimen. Participants may be enrolled in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Tulisokibart (Drug)
Study 2: Low Dose Extension
Participants receive a low dose SC tulisokibart regimen. Participants may be enrolled in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Placebo (Drug)
结局指标
主要结局
Study 1: Percentage of Participants Achieving Clinical Remission Per Modified Mayo Score (MMS) at Week 12
时间窗: Week 12
The Modified Mayo Score (MMS) is a composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: Endoscopic subscore (ES), scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); Stool frequency subscore (SFS), scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and rectal bleeding subscore (RBS), scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
Study 1: Percentage of Participants Achieving Clinical Remission Per MMS at Week 52
时间窗: Week 52
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
Study 2: Percentage of Participants Achieving Clinical Remission Per MMS at Week 12
时间窗: Week 12
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
次要结局
- Study 1: Percentage of Participants With Endoscopic Remission at Week 12(Week 12)
- Study 1: Percentage of Participants Reporting No Bowel Urgency at Week 12(Week 12)
- Study 1: Percentage of Participants Reporting No Abdominal Pain at Week 12(Week 12)
- Study 1: Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Week 12(Week 12)
- Study 1: Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Week 12(Baseline and Week 12)
- Study 1: Percentage of Participants With One or More Adverse Events (AEs)(Up to approximately 52 weeks)
- Study 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE(Up to approximately 52 weeks)
- Study 1: Percentage of Participants Achieving Clinical Response Per Partial Modified Mayo Score (pMMS) at Week 2(Week 2)
- Study 1: Percentage of Participants With Endoscopic Improvement at Week 12(Week 12)
- Study 1: Percentage of Participants Achieving a Clinical Response Per MMS at Week 12(Week 12)
- Study 1: Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement (HEMI) at Week 12(Week 12)
- Study 1: Percentage of Participants Achieving Clinical Remission Per pMMS at Week 12(Week 12)
- Percentage of Diagnostic Assay Positive (Dx+) Participants Achieving Clinical Remission Per MMS at Week 12(Week 12)
- Percentage of Dx+ Participants With Endoscopic Improvement at Week 12(Week 12)
- Study 1: Percentage of Participants Achieving Histologic-Endoscopic Remission (HER) at Week 12(Week 12)
- Study 1: Percentage of Participants with Endoscopic Improvement at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission Per MMS at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving HEMI at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Clinical Remission Per pMMS at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Sustained Clinical Remission Per MMS at Both Week 12 and Week 52(Week 12 and Week 52)
- Study 1: Percentage of Participants Reporting No Bowel Urgency at Week 52(Week 52)
- Study 1: Percentage of Participants Reporting No Abdominal Pain at Week 52(Week 52)
- Study 1: Percentage of Participants With Endoscopic Remission at Week 52(Week 52)
- Study 1: Percentage of Participants with Sustained Endoscopic Improvement at Both Week 12 and Week 52(Week 12 and Week 52)
- Study 1: Percentage of Participants Achieving HER at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving IBDQ Remission at Week 52(Week 52)
- Study 1: Change from Baseline in FACIT-Fatigue Score at Week 52(Baseline and Week 52)
- Study 1: Percentage of Dx+ Participants Achieving Clinical Remission Per MMS at Week 52(Week 52)
- Study 1: Percentage of Dx+ Participants With Endoscopic Improvement at Week 52(Week 52)
- Study 2: Percentage of Participants With One or More AEs(Up to approximately 12 weeks)
- Study 2: Percentage of Participants Who Discontinued Study Intervention Due to an AE(Up to approximately 12 weeks)
- Study 2: Percentage of Participants with Clinical Response Per pMMS at Week 2(Week 2)
- Study 2: Percentage of Participants With Endoscopic Improvement at Week 12(Week 12)
- Study 2: Percentage of Participants Achieving a Clinical Response Per MMS at Week 12(Week 12)
- Study 2: Percentage of Participants Achieving HEMI at Week 12(Week 12)
- Study 2: Percentage of Participants Achieving Clinical Remission Per pMMS at Week 12(Week 12)
- Study 2: Percentage of Participants With Endoscopic Remission at Week 12(Week 12)
- Study 2: Percentage of Participants Reporting No Bowel Urgency at Week 12(Week 12)
- Study 2: Percentage of Participants Reporting No Abdominal Pain at Week 12(Week 12)
- Study 2: Percentage of Participants Achieving IBDQ Remission at Week 12(Week 12)
- Study 2: Change from Baseline in FACIT-Fatigue Score at Week 12(Baseline and Week 12)
- Study 2: Percentage of Participants Achieving HER at Week 12(Week 12)