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

• Register: ClinicalTrials.gov
• Last refreshed on: 2 September 2024
• Main ID: NCT04924114
• Date of registration: 26/02/2021
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme LLC
• Public title: A Study of MK-6194 (PT101) in Participants With Active Ulcerative Colitis (UC) (MK-6194-002)
• Scientific title: 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
• Date of first enrolment: October 14, 2021
• Target sample size: 57
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT04924114
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

Georgia, Germany, Hungary, Moldova, Republic of, Poland, Ukraine, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme LLC

Key inclusion & exclusion 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

- 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.


Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

Intervention(s)

Drug: MK-6194

Drug: MK-6194-matching placebo

Primary Outcome(s)

Percentage of Participants Discontinuing Study Treatment Due to an AE [Time Frame: Up to approximately 85 days]

Percentage of Participants Experiencing Adverse Events (AEs) [Time Frame: Up to approximately 85 days]

Secondary Outcome(s)

Change in Number of Natural Killer (NK) Cells in Whole Blood [Time Frame: Baseline and up to 85 days (last study visit)]

Apparent Volume of Distribution (Vd/F) of MK-6194 [Time Frame: At designated time points (up to 85 days)]

Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194 [Time Frame: At designated time points (up to 85 days)]

Maximum Concentration (Cmax) of MK-6194 [Time Frame: At designated time points (up to 85 days)]

Minimum Concentration (Cmin) of MK-6194 [Time Frame: At designated time points (up to 85 days)]

Time to Cmax (Tmax) of MK-6194 [Time Frame: At designated time points (up to 85 days)]

Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood [Time Frame: Baseline and up to 85 days (last study visit)]

Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) [Time Frame: At designated time points (up to 85 days)]

Titer of anti-drug antibody (ADA) to MK-6194 [Time Frame: At designated time points (up to 85 days)]

Apparent Clearance (CL/F) of MK-6194 [Time Frame: At designated time points (up to 85 days)]

Apparent Half-life (t1/2) of MK-6194 [Time Frame: At designated time points (up to 85 days)]

Change in Number of Conventional T Cells (Tcons) in Whole Blood [Time Frame: Baseline and up to 85 days (last study visit)]

Secondary ID(s)

2021-000093-28

PT101-201

6194-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors