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

Merck Sharp & Dohme LLC57 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Ulcerative Colitis

Interventions

MK-6194DRUG

Subcutaneous injection

MK-6194-matching placeboDRUG

Subcutaneous injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (17)

Inland Empire Clinical Trials, LLC ( Site 0102)

Rialto, California, United States

IHS. Health, LLC ( Site 0104)

Kissimmee, Florida, United States

Outcomes

Primary Outcomes

Number of Participants Who Experienced an Adverse Event (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.

Time frame: Up to approximately 85 days

Number of Participants Who Interrupted or Discontinued 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 thestudy intervention

Time frame: Up to approximately 72 days

Secondary Outcomes

Maximum Concentration (Cmax) of MK-6194

Blood samples were collected at pre-specified time points to determine each participant's maximum concentration (Cmax). A participant's Cmax was defined as the maximum concentration of MK-6194 observed in serum over the entire course of the study for that individual and was calculated by taking the maximum over all observed MK-6194 serum concentrations. Geometric mean and geometric coefficient of variation of Cmax were calculated for each dosing group.

Time frame: 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

Blood samples were collected at pre-specified time points to determine maximum concentration (Cmax) of MK-6194 in each participant's serum and corresponding time of maximum concentration (Tmax). A participant's Tmax was defined as the time post-dose that the maximum concentration of MK-6194 was observed in serum. The median and range of Tmax were calculated for each dosing group.

Time frame: 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

Data from ClinicalTrials.gov

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Carolina's GI Research, LLC ( Site 0105)

Raleigh, North Carolina, United States

Pinnacle Clinical Research ( Site 0103)

San Antonio, Texas, United States

Southern Star Research Institute ( Site 0101)

San Antonio, Texas, United States

ARENSIA Exploratory Medicine Georgia ( Site 0801)

Tbilisi, Georgia

Charite Research Organisation GmbH ( Site 0201)

Berlin, Germany

PRA Magyarorszag Kutatasi es Fejlesztesi Kft. ( Site 0302)

Budapest, Hungary

ARENSIA Exploratory Medicine ( Site 0401)

Chisinau, Moldova

Allmedica Badania Kliniczne Sp z o. o. Sp. K. ( Site 0502)

Nowy Targ, Lesser Poland Voivodeship, Poland

...and 7 more locations

Minimum Concentration (Cmin) of MK-6194

Blood samples were collected at pre-specified time points to determine the minimum concentration (Cmin) of MK-6194 present in each participant's serum. A participant's Cmin was defined as the minimum concentration of MK-6194 observed in serum over the entire course of the study for that individual and was calculated by taking the minimum over all observed MK-6194 serum concentrations. Geometric mean and geometric coefficient of variation of Cmin were calculated for each dosing group.

Time frame: 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

Blood samples were collected at pre-specified time points to determine the apparent half-life (t1/2) of MK-6194. Noncompartmental analysis was used to calculate t1/2 for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of t1/2 were calculated for each dosing group.

Time frame: 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

Blood samples were collected at pre-specified time points to determine the apparent clearance (CL/F) of MK-6194 observed in serum. Noncompartmental analysis was used to calculate CL/F for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of CL/F were calculated for each dosing group.

Time frame: 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

Blood samples were collected at pre-specified time points to determine the apparent volume of distribution (Vd/F) of MK-6194 observed in serum. Noncompartmental analysis was used to calculate Vd/F for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of Vd/F were calculated for each dosing group.

Time frame: 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)

Blood samples were collected at pre-specified timepoints to determine the AUC0-t of MK-6194. AUC0-t is defined as the area under the concentration-time curve from time=0 (Day 1 predose) to the last quantifiable concentration. Noncompartmental analysis was used to calculate AUC0-t for each participant. Geometric mean and geometric coefficient of variation of AUC0-t were calculated for each dosing group.

Time frame: 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

Blood samples were collected at pre-specified timepoints to determine the AUC0-inf of MK-6194. AUC0-inf is defined as the area under the concentration-time curve from time=0 (Day 1 predose) to time=infinity. Noncompartmental analysis was used to calculate AUC0-inf for each participant; the portion of the AUC following the last observed concentration was assumed to follow an exponential elimination. Geometric mean and geometric coefficient of variation of AUC0-inf were calculated for each dosing group.

Time frame: 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

Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The absolute change in the number of peripheral Tregs in whole blood was assessed.

Time frame: 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

Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The change in the number of NK cells in whole blood is presented.

Time frame: 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

Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The change in the number of Tcons in whole blood is presented.

Time frame: 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

Blood samples were collected for the determination of ADA to MK-6194 using a screening assay, ADA titer using a confirmatory assay, and neutralizing antibody to MK-6194 in participants with confirmed positive titers

Time frame: Pre dose (week 0) and Weeks 4, 8, 12