Clinical trial NCT04924114: A Study of MK-6194 (PT101) in Participants With Active Ulcerative Colitis (UC) (MK-6194-002)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-06-11
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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
  * 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.

Primary outcomes:
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 85 days
measure: Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 72 days
Secondary outcomes:
measure: Maximum Concentration (Cmax) of MK-6194
timeFrame: At designated time points (up to 85 days)
measure: Time to Cmax (Tmax) of MK-6194
timeFrame: At designated time points (up to 85 days)
measure: Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t)
timeFrame: At designated time points (up to 85 days)
measure: Minimum Concentration (Cmin) of MK-6194
timeFrame: At designated time points (up to 85 days)
measure: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194
timeFrame: At designated time points (up to 85 days)
measure: Apparent Half-life (t1/2) of MK-6194
timeFrame: At designated time points (up to 85 days)
measure: Apparent Clearance (CL/F) of MK-6194
timeFrame: At designated time points (up to 85 days)
measure: Apparent Volume of Distribution (Vd/F) of MK-6194
timeFrame: At designated time points (up to 85 days)
measure: Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood
timeFrame: Baseline and up to 85 days (last study visit)
measure: Change in Number of Natural Killer (NK) Cells in Whole Blood
timeFrame: Baseline and up to 85 days (last study visit)
measure: Change in Number of Conventional T Cells (Tcons) in Whole Blood
timeFrame: Baseline and up to 85 days (last study visit)
measure: Titer of Anti-drug Antibody (ADA) to MK-6194
timeFrame: At designated time points (up to 85 days)
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Clinical Trials, LLC ( Site 0102)
state: California
city: Kissimmee
country: United States
facility: IHS. Health, LLC ( Site 0104)
state: Florida
city: Raleigh
country: United States
facility: Carolina's GI Research, LLC ( Site 0105)
state: North Carolina
city: San Antonio
country: United States
facility: Pinnacle Clinical Research ( Site 0103)
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute ( Site 0101)
state: Texas
city: Tbilisi
country: Georgia
facility: ARENSIA Exploratory Medicine Georgia ( Site 0801)
city: Berlin
country: Germany
facility: Charite Research Organisation GmbH ( Site 0201)
city: Budapest
country: Hungary
facility: PRA Magyarorszag Kutatasi es Fejlesztesi Kft. ( Site 0302)
city: Chisinau
country: Moldova, Republic of
facility: ARENSIA Exploratory Medicine ( Site 0401)
city: Nowy Targ
country: Poland
facility: Allmedica Badania Kliniczne Sp z o. o. Sp. K. ( Site 0502)
state: Malopolskie
city: Warszawa
country: Poland
facility: WIP Warsaw IBD Point Professor Kierkus ( Site 0501)
state: Mazowieckie
city: Kyiv
country: Ukraine
facility: Arensia Exploratory Medicine GmbH Ukraine ( Site 0701)
state: Kyivska Oblast
city: Prescot
country: United Kingdom
facility: MAC Clinical Research Prescot ( Site 0604)
state: Knowsley
city: Blackpool
country: United Kingdom
facility: Memory Assessment Clinics Ltd ( Site 0601)
state: Lancashire
city: Barnsley
country: United Kingdom
facility: MAC Clinical Research ( Site 0602)
city: Leeds
country: United Kingdom
facility: MAC Clinical Research Centre Leeds ( Site 0603)
city: Manchester
country: United Kingdom
facility: MAC Clinical Research Ltd. ( Site 0605)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: