A Study of MK-6194 (PT101) in Participants With Active Ulcerative Colitis (UC) (MK-6194-002)
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of MK-6194 in participants with active UC.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MK-6194 Participants will be enrolled in sequential cohorts treated with successively higher doses of MK-6194 via subcutaneous injection. |
Drug: MK-6194
Subcutaneous injection
Other Names:
|
| Placebo Comparator: Placebo Participants will receive MK-6194-matching placebo via subcutaneous injection. |
Drug: MK-6194-matching placebo
Subcutaneous injection
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Experiencing Adverse Events (AEs) [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.
- Percentage of Participants Discontinuing Study Treatment Due to an AE [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.
Secondary Outcome Measures
- Maximum Concentration (Cmax) of MK-6194 [At designated time points (up to 85 days)]
Cmax is defined as the maximum concentration of MK-6194 observed in plasma.
- Time to Cmax (Tmax) of MK-6194 [At designated time points (up to 85 days)]
Tmax is defined as the time of maximum concentration of MK-6194 observed in plasma.
- Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) [At designated time points (up to 85 days)]
AUC0-t is defined as the area under concentration-time curve from 0 to last quantifiable concentration.
- Minimum Concentration (Cmin) of MK-6194 [At designated time points (up to 85 days)]
Cmin is defined as the minimum concentration of MK-6194 observed in plasma.
- Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194 [At designated time points (up to 85 days)]
AUC0-inf is a measure of the total amount of MK-6194 in the plasma from time zero to infinity.
- Apparent Half-life (t1/2) of MK-6194 [At designated time points (up to 85 days)]
t1/2 is defined as the time required for the plasma concentration of MK-6194 to decrease by 50%.
- Apparent Clearance (CL/F) of MK-6194 [At designated time points (up to 85 days)]
CL/F is defined as the apparent clearance of MK-6194 observed in plasma.
- Apparent Volume of Distribution (Vd/F) of MK-6194 [At designated time points (up to 85 days)]
Vd/F is defined as the apparent volume of distribution of MK-6194 observed in plasma.
- Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood [Baseline and up to 85 days (last study visit)]
The change in the number of peripheral Tregs in whole blood will be assessed.
- Change in Number of Natural Killer (NK) Cells in Whole Blood [Baseline and up to 85 days (last study visit)]
The change in the number of NK cells in whole blood will be assessed.
- Change in Number of Conventional T Cells (Tcons) in Whole Blood [Baseline and up to 85 days (last study visit)]
The change in the number of Tcons in whole blood will be assessed.
- Titer of anti-drug antibody (ADA) to MK-6194 [At designated time points (up to 85 days)]
ADA of MK-6194 will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of UC at least 3 months prior to screening.
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Mildly to severely active UC.
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Inadequate response, loss of response, or intolerance to at least 1 prior conventional therapy, and no more than 2 prior advanced therapies.
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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.
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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.
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No evidence of active tuberculosis (TB), latent TB, or inadequately treated TB.
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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.
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Body mass index (BMI) 18 to 35 kg/m^2 inclusive and weight ≥ 50 kg.
Exclusion Criteria:
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Prior treatment with recombinant IL-2 or modified IL-2 therapy, including MK-6194 (PT101).
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Known sensitivity to MK-6194 (PT101) or its excipients.
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Known history of hypersensitivity to interleukin-2 (IL-2).
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Disease limited to the rectum (i.e., within 15 cm of the anal verge).
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Diagnosis of toxic megacolon.
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Suspected or known colon stricture or stenosis.
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Diagnosis of Crohn's disease, or indeterminant colitis.
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Has severe colitis as evidenced by:
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Current hospitalization for the treatment of UC
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Likely to require a colectomy within 12 weeks of baseline in the opinion of the Investigator
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At least 4 symptoms of severe colitis as identified at screening or baseline visits.
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Previously had surgery for UC, or likely to require surgery for UC during the study period in the opinion of the Investigator.
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History of abnormal thallium stress test or functional cardiac function test.
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History of significant cardiac, pulmonary, renal, hepatic, or central nervous system (CNS) impairment.
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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.
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History of opportunistic infection.
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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.
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Currently on any chronic systemic (oral or IV) anti-infective therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes zoster, or atypical mycobacteria).
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Currently receiving lymphocyte depleting therapy.
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History of abnormal pulmonary function tests.
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Participants with organ or tissue allograft.
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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.
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Exposure to advanced therapy within 5 half-lives of the Day 1 visit, or documentation of detectable drug during screening.
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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.
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Is pregnant or nursing or is planning to become pregnant during the study.
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Any uncontrolled or clinically significant concurrent systemic disease other than UC.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Inland Empire Clinical Trials, LLC ( Site 0102) | Rialto | California | United States | 92377 |
| 2 | IHS. Health, LLC ( Site 0104) | Kissimmee | Florida | United States | 34741 |
| 3 | Carolina's GI Research, LLC ( Site 0105) | Raleigh | North Carolina | United States | 27607 |
| 4 | Pinnacle Clinical Research ( Site 0103) | San Antonio | Texas | United States | 78229 |
| 5 | Southern Star Research Institute ( Site 0101) | San Antonio | Texas | United States | 78229 |
| 6 | ARENSIA Exploratory Medicine Georgia ( Site 0801) | Tbilisi | Georgia | 0112 | |
| 7 | Charite Research Organisation GmbH ( Site 0201) | Berlin | Germany | 10117 | |
| 8 | PRA Magyarorszag Kutatasi es Fejlesztesi Kft. ( Site 0302) | Budapest | Hungary | 1007 | |
| 9 | ARENSIA Exploratory Medicine ( Site 0401) | Chisinau | Moldova, Republic of | 2025 | |
| 10 | WIP Warsaw IBD Point Professor Kierkus ( Site 0501) | Warszawa | Mazowieckie | Poland | 00-728 |
| 11 | Arensia Exploratory Medicine GmbH Ukraine ( Site 0701) | Kyiv | Kyivska Oblast | Ukraine | 01135 |
| 12 | MAC Clinical Research Prescot ( Site 0604) | Prescot | Knowsley | United Kingdom | L34 1BH |
| 13 | MAC Clinical Research ( Site 0602) | Barnsley | United Kingdom | S75 3DL | |
| 14 | MAC Clinical Research Centre Leeds ( Site 0603) | Leeds | United Kingdom | LS10 1DU | |
| 15 | MAC Clinical Research Ltd. ( Site 0605) | Manchester | United Kingdom | M13 9NQ |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 6194-002
- PT101-201
- 2021-000093-28