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

Phase 1

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: MK-6194
Drug: MK-6194-matching placebo

Registration Number: NCT04924114

Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 57

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
MK-6194 Low Dose - Interval 1	MK-6194	Participants received low dose of MK-6194 at specified intervals
MK-6194 Medium Dose- Interval 2	MK-6194	Participants received medium dose of MK-6194 at specified intervals
MK-6194 High Dose- Interval 2	MK-6194	Participants received high dose of MK-6194 at specified intervals
MK-6194 High Dose- Interval 1	MK-6194	Participants received high dose MK-6194 at specified intervals
Placebo	MK-6194-matching placebo	Participants received MK- 6194-matching placebo via subcutaneous injection, administered either at interval 1 or interval 2

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced an Adverse Event (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.
Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE	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 the study intervention.

Secondary Outcome Measures

Name	Time	Method
Maximum Concentration (Cmax) of MK-6194	At designated time points (up to 85 days)	Blood samples were collected at pre-specified time points to determine the Cmax. Cmax was 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)	Bood samples were collected at pre-specified timepoints to determine the Tmax of MK-6194. Tmax was 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)	Blood samples were collected at pre-specified timepoints to determine the AUC0-t of MK-6194. 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)	Blood samples were collected at pre-specified time points to determine the Cmax. 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)	Blood samples were collected at pre-specified time points to determine the AUC0-inf. 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)	Blood samples were collected at pre-specified time points to determine the t1/2. 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)	Blood samples were collected at pre-specified time points to determine the CL/F. 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)	Whole blood was collected and analyzed by flow cytometry. The change in the number of NK cells in whole blood is presented
Change in Number of Conventional T Cells (Tcons) in Whole Blood	Baseline and up to 85 days (last study visit)	Whole blood was collected and analyzed by flow cytometry. The change in the number of Tcons in whole blood is presented.
Titer of Anti-drug Antibody (ADA) to MK-6194	At designated time points (up to 85 days)	Blood samples were collected for the determination of ADA to MK-6194 using a confirmatory assay. Neutralizing antibody to MK-6194 was assessed in subjects with confirmed positive titers

Trial Locations

Locations (17): IHS. Health, LLC ( Site 0104)
🇺🇸
Kissimmee, Florida, United States
Pinnacle Clinical Research ( Site 0103)
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San Antonio, Texas, United States
Charite Research Organisation GmbH ( Site 0201)
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Berlin, Germany
MAC Clinical Research Ltd. ( Site 0605)
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Manchester, United Kingdom
MAC Clinical Research Centre Leeds ( Site 0603)
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Leeds, United Kingdom
MAC Clinical Research ( Site 0602)
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Barnsley, United Kingdom
Carolina's GI Research, LLC ( Site 0105)
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Raleigh, North Carolina, United States
Inland Empire Clinical Trials, LLC ( Site 0102)
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Rialto, California, United States
ARENSIA Exploratory Medicine ( Site 0401)
🇲🇩
Chisinau, Moldova, Republic of
WIP Warsaw IBD Point Professor Kierkus ( Site 0501)
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Warszawa, Mazowieckie, Poland
Southern Star Research Institute ( Site 0101)
🇺🇸
San Antonio, Texas, United States
ARENSIA Exploratory Medicine Georgia ( Site 0801)
🇬🇪
Tbilisi, Georgia
MAC Clinical Research Prescot ( Site 0604)
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Prescot, Knowsley, United Kingdom
Memory Assessment Clinics Ltd ( Site 0601)
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Blackpool, Lancashire, United Kingdom
Allmedica Badania Kliniczne Sp z o. o. Sp. K. ( Site 0502)
🇵🇱
Nowy Targ, Malopolskie, Poland
PRA Magyarorszag Kutatasi es Fejlesztesi Kft. ( Site 0302)
🇭🇺
Budapest, Hungary
Arensia Exploratory Medicine GmbH Ukraine ( Site 0701)
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Kyiv, Kyivska Oblast, Ukraine