A Study of MK-6194 (PT101) in Participants With Active Ulcerative Colitis (UC) (MK-6194-002)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of MK-6194 in participants with active UC.

Official Title
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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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: MK-6194
* Drug: MK-6194-matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-6194<br>Participants will be enrolled in sequential cohorts treated with successively higher doses of MK-6194 via subcutaneous injection. | Drug: MK-6194<br>* Subcutaneous injection<br>* Other names: PT101;|
| Placebo Comparator: Placebo<br>Participants will receive MK-6194-matching placebo via subcutaneous injection. | Drug: MK-6194-matching placebo<br>* Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Adverse Events (AEs) | 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. | Up to approximately 85 days | 
| Percentage of Participants Discontinuing Study Treatment Due to an AE | 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. | Up to approximately 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration (Cmax) of MK-6194 | Cmax is defined as the maximum concentration of MK-6194 observed in plasma. | At designated time points (up to 85 days) | 
| Time to Cmax (Tmax) of MK-6194 | Tmax is defined as the time of maximum concentration of MK-6194 observed in plasma. | At designated time points (up to 85 days) | 
| Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) | AUC0-t is defined as the area under concentration-time curve from 0 to last quantifiable concentration. | At designated time points (up to 85 days) | 
| Minimum Concentration (Cmin) of MK-6194 | Cmin is defined as the minimum concentration of MK-6194 observed in plasma. | At designated time points (up to 85 days) | 
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194 | AUC0-inf is a measure of the total amount of MK-6194 in the plasma from time zero to infinity. | At designated time points (up to 85 days) | 
| Apparent Half-life (t1/2) of MK-6194 | t1/2 is defined as the time required for the plasma concentration of MK-6194 to decrease by 50%. | At designated time points (up to 85 days) | 
| Apparent Clearance (CL/F) of MK-6194 | CL/F is defined as the apparent clearance of MK-6194 observed in plasma. | At designated time points (up to 85 days) | 
| Apparent Volume of Distribution (Vd/F) of MK-6194 | Vd/F is defined as the apparent volume of distribution of MK-6194 observed in plasma. | At designated time points (up to 85 days) | 
| Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | The change in the number of peripheral Tregs in whole blood will be assessed. | Baseline and up to 85 days (last study visit) | 
| Change in Number of Natural Killer (NK) Cells in Whole Blood | The change in the number of NK cells in whole blood will be assessed. | Baseline and up to 85 days (last study visit) | 
| Change in Number of Conventional T Cells (Tcons) in Whole Blood | The change in the number of Tcons in whole blood will be assessed. | Baseline and up to 85 days (last study visit) | 
| Titer of anti-drug antibody (ADA) to MK-6194 | ADA of MK-6194 will be assessed. | At designated time points (up to 85 days) |