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

Ulcerative Colitis Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04924114
• Other study ID #: 6194-002
• Secondary ID: PT101-2012021-00
• Status: Completed
• Phase: Phase 1
• Start date: October 14, 2021
• Est. completion date: May 14, 2024

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: May 14, 2024
• Est. primary completion date: January 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• MK-6194
Subcutaneous injection
• MK-6194-matching placebo
Subcutaneous injection

Locations

Country	Name	City	State
Georgia	ARENSIA Exploratory Medicine Georgia ( Site 0801)	Tbilisi
Germany	Charite Research Organisation GmbH ( Site 0201)	Berlin
Hungary	PRA Magyarorszag Kutatasi es Fejlesztesi Kft. ( Site 0302)	Budapest
Moldova, Republic of	ARENSIA Exploratory Medicine ( Site 0401)	Chisinau
Poland	Allmedica Badania Kliniczne Sp z o. o. Sp. K. ( Site 0502)	Nowy Targ	Malopolskie
Poland	WIP Warsaw IBD Point Professor Kierkus ( Site 0501)	Warszawa	Mazowieckie
Ukraine	Arensia Exploratory Medicine GmbH Ukraine ( Site 0701)	Kyiv	Kyivska Oblast
United Kingdom	MAC Clinical Research ( Site 0602)	Barnsley
United Kingdom	Memory Assessment Clinics Ltd ( Site 0601)	Blackpool	Lancashire
United Kingdom	MAC Clinical Research Centre Leeds ( Site 0603)	Leeds
United Kingdom	MAC Clinical Research Ltd. ( Site 0605)	Manchester
United Kingdom	MAC Clinical Research Prescot ( Site 0604)	Prescot	Knowsley
United States	IHS. Health, LLC ( Site 0104)	Kissimmee	Florida
United States	Carolina's GI Research, LLC ( Site 0105)	Raleigh	North Carolina
United States	Inland Empire Clinical Trials, LLC ( Site 0102)	Rialto	California
United States	Pinnacle Clinical Research ( Site 0103)	San Antonio	Texas
United States	Southern Star Research Institute ( Site 0101)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Adverse Events (AEs)	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
Primary	Percentage of Participants Discontinuing 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 the study intervention.	Up to approximately 85 days
Secondary	Maximum Concentration (Cmax) of MK-6194	Cmax is defined as the maximum concentration of MK-6194 observed in plasma.	At designated time points (up to 85 days)
Secondary	Time to Cmax (Tmax) of MK-6194	Tmax is defined as the time of maximum concentration of MK-6194 observed in plasma.	At designated time points (up to 85 days)
Secondary	Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t)	AUC0-t is defined as the area under concentration-time curve from 0 to last quantifiable concentration.	At designated time points (up to 85 days)
Secondary	Minimum Concentration (Cmin) of MK-6194	Cmin is defined as the minimum concentration of MK-6194 observed in plasma.	At designated time points (up to 85 days)
Secondary	Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194	AUC0-inf is a measure of the total amount of MK-6194 in the plasma from time zero to infinity.	At designated time points (up to 85 days)
Secondary	Apparent Half-life (t1/2) of MK-6194	t1/2 is defined as the time required for the plasma concentration of MK-6194 to decrease by 50%.	At designated time points (up to 85 days)
Secondary	Apparent Clearance (CL/F) of MK-6194	CL/F is defined as the apparent clearance of MK-6194 observed in plasma.	At designated time points (up to 85 days)
Secondary	Apparent Volume of Distribution (Vd/F) of MK-6194	Vd/F is defined as the apparent volume of distribution of MK-6194 observed in plasma.	At designated time points (up to 85 days)
Secondary	Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood	The change in the number of peripheral Tregs in whole blood will be assessed.	Baseline and up to 85 days (last study visit)
Secondary	Change in Number of Natural Killer (NK) Cells in Whole Blood	The change in the number of NK cells in whole blood will be assessed.	Baseline and up to 85 days (last study visit)
Secondary	Change in Number of Conventional T Cells (Tcons) in Whole Blood	The change in the number of Tcons in whole blood will be assessed.	Baseline and up to 85 days (last study visit)
Secondary	Titer of anti-drug antibody (ADA) to MK-6194	ADA of MK-6194 will be assessed.	At designated time points (up to 85 days)

External Links

•   Merck Clinical Trials Information