NCT04924114已完成1 期
A Phase 1b, Randomized, Adaptive, Double-Blind, Placebo-Controlled, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of PT101 in Subjects With Active Ulcerative Colitis
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 17
- 主要终点
- Number of Participants Who Experienced an Adverse Event (AE)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of MK-6194 in participants with active UC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of UC at least 3 months prior to screening.
- •Mildly to severely active UC.
- •Inadequate response, loss of response, or intolerance to at least 1 prior conventional therapy, and no more than 2 prior advanced therapies.
- •Participants at risk for colorectal cancer must have a colonoscopy prior to or at screening as follows:
- •Participants > 50 years of age must have documentation of a colonoscopy within 3 years of the screening visit to exclude adenomatous polyps. Participants whose adenomas have been completely excised at screening are eligible.
- •Participants with extensive colitis for ≥ 8 years, or disease limited to the left side of the colon for ≥ 10 years, must either have had a full colonoscopy to assess for the presence of dysplasia within 1 year before first administration of study drug or a full colonoscopy to assess for the presence of malignancy at the screening visit.
- •No evidence of active tuberculosis (TB), latent TB, or inadequately treated TB.
- •Women of childbearing potential (WOCBP) and males with female partners of childbearing potential must utilize highly effective contraceptive methods beginning 4 weeks prior to first dose of study drug and continue for 30 days after the last dose of study drug.
- •Body mass index (BMI) 18 to 35 kg/m^2 inclusive and weight ≥ 50 kg.
排除标准
- •Prior treatment with recombinant IL-2 or modified IL-2 therapy, including MK-6194 (PT101).
- •Known sensitivity to MK-6194 (PT101) or its excipients.
- •Known history of hypersensitivity to interleukin-2 (IL-2).
- •Disease limited to the rectum (i.e., within 15 cm of the anal verge).
- •Diagnosis of toxic megacolon.
- •Suspected or known colon stricture or stenosis.
- •Diagnosis of Crohn's disease, or indeterminant colitis.
- •Has severe colitis as evidenced by:
- •Current hospitalization for the treatment of UC
- •Likely to require a colectomy within 12 weeks of baseline in the opinion of the Investigator
- •At least 4 symptoms of severe colitis as identified at screening or baseline visits.
- •Previously had surgery for UC, or likely to require surgery for UC during the study period in the opinion of the Investigator.
- •History of abnormal thallium stress test or functional cardiac function test.
- •History of significant cardiac, pulmonary, renal, hepatic, or central nervous system (CNS) impairment.
- •Active clinically significant infection, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 8 weeks of randomization, or any infection requiring oral anti-infective therapy within 6 weeks of randomization.
- •History of opportunistic infection.
- •History of symptomatic herpes zoster within 16 weeks of randomization, or any history of disseminated herpes simplex, disseminated herpes zoster, ophthalmic zoster, or central nervous system (CNS) zoster.
- •Currently on any chronic systemic (oral or IV) anti-infective therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes zoster, or atypical mycobacteria).
- •Currently receiving lymphocyte depleting therapy.
- •History of abnormal pulmonary function tests.
- •Participants with organ or tissue allograft.
- •Malignancy within 5 years of screening, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin.
- •Exposure to advanced therapy within 5 half-lives of the Day 1 visit, or documentation of detectable drug during screening.
- •Received a live attenuated vaccine < 1 month prior to screening or is planning to receive a live attenuated vaccine during the study period or within 12 weeks of the end of participation in the study.
- •Is pregnant or nursing or is planning to become pregnant during the study.
- •Any uncontrolled or clinically significant concurrent systemic disease other than UC.
研究组 & 干预措施
MK-6194 Low Dose - Interval 1 (Less Frequent)
Experimental
Participants received low dose of MK-6194 at specified less frequent intervals
干预措施: MK-6194 (Drug)
MK-6194 Medium Dose- Interval 2 (More Frequent)
Experimental
Participants received medium dose of MK-6194 at specified more frequent intervals
干预措施: MK-6194 (Drug)
MK-6194 High Dose- Interval 2 (More Frequent)
Experimental
Participants received high dose of MK-6194 at specified more frequent intervals
干预措施: MK-6194 (Drug)
MK-6194 High Dose- Interval 1 (Less Frequent)
Experimental
Participants received high dose MK-6194 at specified less frequent intervals
干预措施: MK-6194 (Drug)
Placebo
Placebo Comparator
Participants received MK- 6194-matching placebo via subcutaneous injection, administered either at interval 1 or interval 2
干预措施: MK-6194-matching placebo (Drug)
结局指标
主要结局
Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 85 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE
时间窗: Up to approximately 72 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to thestudy intervention
次要结局
- Maximum Concentration (Cmax) of MK-6194(Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85.)
- Time to Cmax (Tmax) of MK-6194(Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85)
- Minimum Concentration (Cmin) of MK-6194(Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85)
- Apparent Half-life (t1/2) of MK-6194(Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85)
- Apparent Clearance (CL/F) of MK-6194(Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85)
- Apparent Volume of Distribution (Vd/F) of MK-6194(Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85)
- Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t)(Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85)
- Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194(Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85)
- Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood(Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- Change in Number of Natural Killer (NK) Cells in Whole Blood(Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- Change in Number of Conventional T Cells (Tcons) in Whole Blood(Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- Titer of Anti-drug Antibody (ADA) to MK-6194(Pre dose (week 0) and Weeks 4, 8, 12)
研究者
研究点 (17)
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