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).
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Percentage Change from Baseline in Colorectal Polyp Burden for all Polyps at
Week 24
- Percentage Change from Baseline in Colorectal Polyp Burden for Polyps >=2 mm
at Week 24
Secondary outcome
- Percentage Change in Number of Colon Polyps
- Percentage Change in Number of Rectal Polyps
- Percentage Change in Number of J-pouch Polyps
- Percentage Change in Number of Duodenal Polyps
- Percentage Change in Colon Polyp Burden for all Polyps, Polyps >=2 mm and
Polyps >=5 mm
- Percentage Change in Rectal Polyp Burden for all Polyps, Polyps >=2 mm and
Polyps >=5 mm
- Percentage Change in J-Pouch Polyp Burden for all Polyps, Polyps >=2 mm and
Polyps >=5 mm
- Percentage Change in Duodenal Polyp Burden for all Polyps, Polyps >=2 mm and
Polyps >=5 mm
- Change in International Society for Gastrointestinal Hereditary Tumors
(InSiGHT) Polyposis Stage (with and Without Colon)
- Change in Spigelman Stage Score
- Number of Participants with Adverse Events (AEs)
- Number of Participants with AEs by Severity
- Plasma Concentration of JNJ-64251330 Over Time
- Tissue Concentration of JNJ-64251330 Over Time
- Levels of JAK/STAT Pathway Signaling Effector Proteins including pSTAT-3
Relative to Baseline Levels in Colorectal Polyps
Background summary
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.
Study objective
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).
Study design
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.
Intervention
JNJ-64251330 (Other name: Lorpucitinib): tablets will be administered orally.
Study burden and risks
See protocol and IB.
Graaf Engelbertlaan 75
Breda 4928 DS
NL
Graaf Engelbertlaan 75
Breda 4928 DS
NL
Listed location countries
Age
Inclusion 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
Exclusion Criteria:
- Use of non-steroidal anti-inflammatory drugs (example, aspirin, ibuprofen)
exceeding 5 days per month, or exceeding the nonprescription dose, unless
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 (including increased risk of
thrombosis), 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)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-001068-16-NL |
| ClinicalTrials.gov | NCT05014360 |
| CCMO | NL78576.018.21 |