Clinical Trials/NCT04924114

NCT04924114

Completed

Phase 1

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

Merck Sharp & Dohme LLC17 sites in 8 countries57 target enrollmentOctober 14, 2021

ConditionsUlcerative Colitis

InterventionsMK-6194 MK-6194-matching placebo

DrugsMK-6194 MK-6194-matching placebo

Overview

Phase: Phase 1
Intervention: MK-6194
Conditions: Ulcerative Colitis
Sponsor: Merck Sharp & Dohme LLC
Enrollment: 57
Locations: 17
Primary Endpoint: Number of Participants Who Experienced an Adverse Event (AE)
Status: Completed
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 14, 2021

End Date

July 15, 2024

Last Updated

8 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Merck Sharp & Dohme LLC

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

MK-6194 Low Dose - Interval 1 (Less Frequent)

Participants received low dose of MK-6194 at specified less frequent intervals

Intervention: MK-6194

MK-6194 Medium Dose- Interval 2 (More Frequent)

Participants received medium dose of MK-6194 at specified more frequent intervals

Intervention: MK-6194

MK-6194 High Dose- Interval 2 (More Frequent)

Participants received high dose of MK-6194 at specified more frequent intervals

Intervention: MK-6194

MK-6194 High Dose- Interval 1 (Less Frequent)

Participants received high dose MK-6194 at specified less frequent intervals

Intervention: MK-6194

Placebo

Participants received MK- 6194-matching placebo via subcutaneous injection, administered either at interval 1 or interval 2

Intervention: MK-6194-matching placebo

Outcomes

Primary Outcomes

Number of Participants Who Experienced an Adverse Event (AE)

Time Frame: 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

Time Frame: 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 thestudy intervention

Secondary Outcomes

Maximum Concentration (Cmax) of MK-6194(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(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(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(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(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(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)(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(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(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(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(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(Pre dose (week 0) and Weeks 4, 8, 12)