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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Ulcerative Colitis

Treatments: Drug: MK-6194-matching placebo; Drug: MK-6194

Study type: Interventional

Funder types: Industry

Identifiers

NCT04924114

PT101-201 (Other Identifier)

2021-000093-28 (EudraCT Number)

6194-002

Details and patient eligibility

About

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

Enrollment: 57 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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57 participants in 5 patient groups, including a placebo group

MK-6194 1 mg every 4 weeks (Q4W)

Experimental group

Description:

Participants received 1 mg MK-6194 every 4 weeks (Q4W)

Treatment:

Drug: MK-6194

MK-6194 2.5 mg every 2 weeks (Q2W)

Experimental group

Description:

Participants received 2.5 mg MK-6194 every 2 weeks (Q2W)

Treatment:

Drug: MK-6194

MK-6194 5 mg Q2W

Experimental group

Description:

Participants received 5mg MK-6194 Q2W

Treatment:

Drug: MK-6194

MK-6194 5 mg Q4W

Experimental group

Description:

Participants received 5 mg MK-6194 Q4W

Treatment:

Drug: MK-6194

Placebo

Placebo Comparator group

Description:

Participants received MK- 6194-matching placebo via subcutaneous injection, administered either Q2W or Q4W

Treatment:

Drug: MK-6194-matching placebo