Clinical trial NCT05014360: A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis
Official title: A Phase 1b Study to Evaluate the Efficacy and Safety of JNJ-64251330, a Janus Kinase (JAK) Inhibitor, in Participants With Familial Adenomatous Polyposis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adenomatous Polyposis Coli
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-08-20
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effect of JNJ-64251330 in participants with Familial Adenomatous Polyposis (FAP) on colorectal polyp burden (sum of the polyp diameters).

Detailed description: Familial adenomatous polyposis (FAP) is the most common polyposis syndrome. It is an autosomal dominant inherited disorder characterized by the early onset of hundreds to thousands of adenomatous polyps throughout the colon. JNJ-64251330 (lorpucitinib) is an oral, small molecule, potent pan-janus kinase (JAK) inhibitor that blocks phosphorylation of Signal Transducer and Activator of Transcription (STAT) proteins. pSTAT induces transcription of multiple genes involved in the progression of inflammatory disease. JNJ-64251330 has chemical properties that limits the amount of drug in the blood while delivering the drug to the tissues of the gut. Local inhibition of JAK in the gut may present a promising method to treat inflammatory diseases of the intestinal tract, such as FAP. The study consists of 3 phases: screening phase (30 days) a treatment phase (24 weeks), and follow-up visit (up to 30 days after last dose of study drug). The total duration of the study will be up to 32 weeks. Study evaluations will include efficacy via endoscopies, safety (monitoring of adverse events (AE), serious adverse events (SAEs), events of infections including tuberculosis (TB), clinical laboratory blood tests (complete blood count and serum chemistries), vital signs, and concomitant medication review), pharmacokinetics, pharmacodynamic and biomarkers evaluations.

Eligibility criteria: Inclusion Criteria:

* Genetic diagnosis of classical familial adenomatous polyposis (FAP) (adenomatous polyposis coli \[APC\] germline mutation or obligate carrier) with disease involvement of the colorectum
* At least 6 polyps greater than or equal to (\>=) 2 millimeters (mm) in diameter in the rectum or colon
* A female participant of childbearing potential must have a negative highly sensitive pregnancy test at screening and within 72 hours prior to the first dose of study drug and must agree to further pregnancy tests during the study
* A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study drug
* Must sign an informed consent form (ICF) indicating he or she understands the purpose of the study and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard of care for the participant's disease

Exclusion Criteria:

* Use of non-steroidal anti-inflammatory drugs (example, aspirin, ibuprofen) exceeding 5 days per month or exceeding the nonprescription dose, unless the participant completes a 4-week washout period prior to the first dose of study drug
* Treatment with other FAP-directed drug therapy (including sulindac or celecoxib), unless completes a 4-week washout period prior to the first dose of study drug
* History of human immunodeficiency virus (HIV)
* History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
* A history of, or ongoing, chronic or recurrent infectious disease including latent or active tuberculosis (TB)

Primary outcomes:
measure: Percentage Change from Baseline in Colorectal Polyp Burden for all Polyps at Week 24
timeFrame: Baseline and Week 24
measure: Percentage Change from Baseline in Colorectal Polyp Burden for Polyps >=2 mm at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Percentage Change in Number of Colon Polyps
timeFrame: Baseline and Week 24
measure: Percentage Change in Number of Rectal Polyps
timeFrame: Baseline and Week 24
measure: Percentage Change in Number of J-pouch Polyps
timeFrame: Baseline and Week 24
measure: Percentage Change in Number of Duodenal Polyps
timeFrame: Baseline and Week 24
measure: Percentage Change in Colon Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
timeFrame: Baseline and Week 24
measure: Percentage Change in Rectal Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
timeFrame: Baseline and Week 24
measure: Percentage Change in J-Pouch Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
timeFrame: Baseline and Week 24
measure: Percentage Change in Duodenal Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
timeFrame: Baseline and Week 24
measure: Change in International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Polyposis Stage (with and Without Colon)
timeFrame: Baseline and Week 24
measure: Change in Spigelman Stage Score
timeFrame: Baseline and Week 24
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 32 weeks
measure: Number of Participants with AEs by Severity
timeFrame: Up to 32 weeks
measure: Plasma Concentration of JNJ-64251330 Over Time
timeFrame: Up to Week 24
measure: Tissue Concentration of JNJ-64251330 Over Time
timeFrame: Up to Week 24
measure: Levels of JAK/STAT Pathway Signaling Effector Proteins including pSTAT-3 Relative to Baseline Levels in Colorectal Polyps
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Lyon
country: France
facility: Hopital Edouard Herriot - CHU Lyon
city: Marseille
country: France
facility: APHM Hopital Timone
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum Universiteit van Amsterdam
city: Río Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials LLC
city: Madrid
country: Spain
facility: Hosp. Clinic I Provincial de Barcelona
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: