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

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

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

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: MK-6194; Drug: MK-6194-matching placebo

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia, 0112
    • ARENSIA Exploratory Medicine Georgia ( Site 0801)
• Germany
  • Berlin, Germany, 10117
    • Charite Research Organisation GmbH ( Site 0201)
• Hungary
  • Budapest, Hungary, 1007
    • PRA Magyarorszag Kutatasi es Fejlesztesi Kft. ( Site 0302)
• Moldova
  • Chisinau, Moldova, 2025
    • ARENSIA Exploratory Medicine ( Site 0401)
• Poland
  • Lesser Poland Voivodeship
    • Nowy Targ, Lesser Poland Voivodeship, Poland, 34-400
      • Allmedica Badania Kliniczne Sp z o. o. Sp. K. ( Site 0502)
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 00-728
      • WIP Warsaw IBD Point Professor Kierkus ( Site 0501)
• Ukraine
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 01135
      • Arensia Exploratory Medicine GmbH Ukraine ( Site 0701)
• United Kingdom
  • Barnsley, United Kingdom, S75 3DL
    • MAC Clinical Research ( Site 0602)
  • Leeds, United Kingdom, LS10 1DU
    • MAC Clinical Research Centre Leeds ( Site 0603)
  • Manchester, United Kingdom, M13 9NQ
    • MAC Clinical Research Ltd. ( Site 0605)
  • Knowsley
    • Prescot, Knowsley, United Kingdom, L34 1BH
      • MAC Clinical Research Prescot ( Site 0604)
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY2 0JH
      • Memory Assessment Clinics Ltd ( Site 0601)
• United States
  • California
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials, LLC ( Site 0102)
  • Florida
    • Kissimmee, Florida, United States, 34741
      • IHS. Health, LLC ( Site 0104)
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Carolina's GI Research, LLC ( Site 0105)
  • Texas
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research ( Site 0103)
    • San Antonio, Texas, United States, 78229
      • Southern Star Research Institute ( Site 0101)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received MK- 6194-matching placebo via subcutaneous injection, administered either at interval 1 or interval 2	Drug: MK-6194-matching placebo; Subcutaneous injection
Experimental: MK-6194 Low Dose - Interval 1 (Less Frequent); Participants received low dose of MK-6194 at specified less frequent intervals	Drug: MK-6194; Subcutaneous injection; Other Names: PT101
Experimental: MK-6194 Medium Dose- Interval 2 (More Frequent); Participants received medium dose of MK-6194 at specified more frequent intervals	Drug: MK-6194; Subcutaneous injection; Other Names: PT101
Experimental: MK-6194 High Dose- Interval 2 (More Frequent); Participants received high dose of MK-6194 at specified more frequent intervals	Drug: MK-6194; Subcutaneous injection; Other Names: PT101
Experimental: MK-6194 High Dose- Interval 1 (Less Frequent); Participants received high dose MK-6194 at specified less frequent intervals	Drug: MK-6194; Subcutaneous injection; Other Names: PT101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Up to approximately 72 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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	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.	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.	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.	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.	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.	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.	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.	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.	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.	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	Pre dose (week 0) and Weeks 4, 8, 12

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2021
• Primary Completion (Actual): January 8, 2024
• Study Completion (Actual): July 15, 2024

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: June 9, 2021
• First Posted (Actual): June 11, 2021

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 6194-002; PT101-201 (Other Identifier: Pandion); 2021-000093-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No