Adenomatous Polyposis ColiPhase 1NCT05014360
A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis
A Phase 1 study testing JNJ-64251330 in people with Adenomatous Polyposis Coli, run by Janssen Research & Development, LLC at 16 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenomatous Polyposis Coli
- What is being tested?
- JNJ-64251330
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 16 sitesin 7 countries
- Study dates
- 10 Nov 2021to 15 Feb 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
16 sites in 7 countries.
16 sites in 7 countries
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
City of Hope
Duarte, California, 91010
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Miami
Miami, Florida, 33136
South Korea4 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
France2 sites
Hopital Edouard Herriot - CHU Lyon
Lyon, 69437
APHM Hopital Timone
Marseille, 13385
Spain2 sites
Hosp. Clinic I Provincial de Barcelona
Madrid, 8036
Clinica Univ. de Navarra
Pamplona, 31008
Netherlands1 site
Academisch Medisch Centrum Universiteit van Amsterdam
Amsterdam, 1105 AZ
Puerto Rico1 site
Pan American Center for Oncology Trials LLC
Río Piedras, 00 935
About this study
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
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).
Read the 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.
- Conditions
- Adenomatous Polyposis Coli
- Being tested
- JNJ-64251330
- Medical subject headings
- Adenomatous Polyposis Coli
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-64251330Drug
Also called Lorpucitinib
JNJ-64251330 tablets will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| JNJ-64251330 | Experimental | Participants will receive oral dose of JNJ-64251330 twice daily for 24 Weeks. Receives: Drug: JNJ-64251330 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change from Baseline in Colorectal Polyp Burden for all Polyps at Week 24
Percentage change from baseline in colorectal polyp burden for all polyps (the sum of the polyp diameters) at Week 24 will be reported.
Measured: Baseline and Week 24
Percentage Change from Baseline in Colorectal Polyp Burden for Polyps >=2 mm at Week 24
Percentage change from baseline in colorectal polyp burden (sum of the polyp diameters) for polyps greater than or equal to (>=) 2 millimeters (mm) at Week 24 will be reported.
Measured: Baseline and Week 24
Secondary outcomes (15)
Percentage Change in Number of Colon Polyps
Percentage change in number of colon polyps will be reported.
Measured: Baseline and Week 24
Percentage Change in Number of Rectal Polyps
Percentage change in number of rectal polyps will be reported.
Measured: Baseline and Week 24
Percentage Change in Number of J-pouch Polyps
Percentage change in number of J-pouch polyps (for participants with an ileal pouch-anal anastomosis [IPAA]) will be reported.
Measured: Baseline and Week 24
Percentage Change in Number of Duodenal Polyps
Percentage change in number of duodenal polyps will be reported.
Measured: Baseline and Week 24
Percentage Change in Colon Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Percentage change in colon polyp burden for all polyps, polyps >=2 mm and polyps >=5 mm will be reported.
Measured: Baseline and Week 24
Percentage Change in Rectal 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 will be reported.
Measured: Baseline and Week 24
Percentage Change in J-Pouch Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Percentage change in J-Pouch polyp (for participants with an IPAA) burden for all polyps, polyps >=2 mm and polyps >=5 mm will be reported.
Measured: Baseline and Week 24
Percentage Change in Duodenal 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 will be reported.
Measured: Baseline and Week 24
Change in International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Polyposis Stage (with and Without Colon)
Change in InSiGHT stage will be reported. Various stages are defined as: a) With Colon: Stage 0: 0-10 polyps,all less than [<]5mm); Stage 1: 20-200 polyps,most <5 mm, none, >1 centimeters[cm]; Stage 2: 200-500 polyps,<10 that are >1 cm; Stage 3: 500-1000 polyps or any number if there are 10-50 that are >1 cm and amenable to complete polypectomy; Stage 4: >1000 polyps and/or any polyps grown to confluence and not amenable to simple polypectomy, any invasive cancer; b) Without Colon: Stage 0: 0 -10 polyps, all <5 mm; Stage 1: 10-25 polyps most <5 mm, none >1 cm; Stage 2: 10-25 polyps, any >1 amenable to complete removal; Stage 3: >25 polyps amenable to complete removal, or any incompletely removed sessile polyp, or any evidence of high-grade dysplasia (HGD), even if completely excised; Stage 4: >25 polyps not amenable complete removal, or any incompletely excised sessile polyp showing HGD; any invasive cancer.
Measured: Baseline and Week 24
Change in Spigelman Stage Score
Change in Spigelman stage score will be reported. Spigelman classification system measures risk of developing duodenal cancer in familial adenomatous polyposis (FAP). It has been classified in following stages- Stage 0 (0 points); Stage 1 (1-4 points); Stage 2 (5-6 points); Stage 3 (7-8 points); and Stage 4 (9-12 points). The total score ranges from 0 to 12. The higher the score, the more severe or advanced the FAP disease in the duodenum.
Measured: Baseline and Week 24
Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Measured: Up to 32 weeks
Number of Participants with AEs by Severity
Number of participants with AEs by severity will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to AE.
Measured: Up to 32 weeks
Plasma Concentration of JNJ-64251330 Over Time
Plasma samples will be analyzed to determine plasma concentrations of JNJ-64251330 using a validated specific, and sensitive liquid chromatography coupled to tandem mass spectrometry detection (LC-MS/MS).
Measured: Up to Week 24
Tissue Concentration of JNJ-64251330 Over Time
Tissue biopsy samples will be analyzed to determine tissue concentrations of JNJ-64251330 using a validated specific, and sensitive LC-MS/MS.
Measured: Up to Week 24
Levels of JAK/STAT Pathway Signaling Effector Proteins including pSTAT-3 Relative to Baseline Levels in Colorectal Polyps
Levels of Pan-janus kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway signaling effector proteins including phosphorylated (p) STAT-3 relative to baseline levels in colorectal polyps will be reported. Polyp and tissue samples will be collected to monitor for changes to the JAK-STAT pathway.
Measured: Up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2021
- Study start10 Nov 2021
- Primary completion15 Feb 2023
- Study completion15 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenomatous Polyposis ColiStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05014360
- Sponsor's protocol ID
- CR109012
- Other IDs
- 2021-001068-16, 64251330COR1001
- Status last verified
- Jun 2023
- First submitted
- 13 Aug 2021
- Last updated
- 2 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05014360
- Acronym / sponsor ID
- CR109012
- Conditions
- Adenomatous Polyposis Coli
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2021 (actual)
- Primary completion
- 15 Feb 2023 (actual)
- Study completion
- 15 Feb 2023 (actual)
- First posted
- 20 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| JNJ-64251330 | Experimental | Drug: JNJ-64251330Participants will receive oral dose of JNJ-64251330 twice daily for 24 Weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JNJ-64251330Also: LorpucitinibJNJ-64251330 tablets will be administered orally. | Drug | JNJ-64251330 |
Primary outcome
Percentage Change from Baseline in Colorectal Polyp Burden for all Polyps at Week 24
Time frame: Baseline and Week 24
Percentage change from baseline in colorectal polyp burden for all polyps (the sum of the polyp diameters) at Week 24 will be reported.
Percentage Change from Baseline in Colorectal Polyp Burden for Polyps >=2 mm at Week 24
Time frame: Baseline and Week 24
Percentage change from baseline in colorectal polyp burden (sum of the polyp diameters) for polyps greater than or equal to (>=) 2 millimeters (mm) at Week 24 will be reported.
15 secondary outcomes
Percentage Change in Number of Colon Polyps
Time frame: Baseline and Week 24
Percentage Change in Number of Rectal Polyps
Time frame: Baseline and Week 24
Percentage Change in Number of J-pouch Polyps
Time frame: Baseline and Week 24
Percentage Change in Number of Duodenal Polyps
Time frame: Baseline and Week 24
Percentage Change in Colon Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Time frame: Baseline and Week 24
Percentage Change in Rectal Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Time frame: Baseline and Week 24
Percentage Change in J-Pouch Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Time frame: Baseline and Week 24
Percentage Change in Duodenal Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Time frame: Baseline and Week 24
Change in International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Polyposis Stage (with and Without Colon)
Time frame: Baseline and Week 24
Change in Spigelman Stage Score
Time frame: Baseline and Week 24
Number of Participants with Adverse Events (AEs)
Time frame: Up to 32 weeks
Number of Participants with AEs by Severity
Time frame: Up to 32 weeks
Plasma Concentration of JNJ-64251330 Over Time
Time frame: Up to Week 24
Tissue Concentration of JNJ-64251330 Over Time
Time frame: Up to Week 24
Levels of JAK/STAT Pathway Signaling Effector Proteins including pSTAT-3 Relative to Baseline Levels in Colorectal Polyps
Time frame: Up to Week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2023.
- Individual participant dataSharing planned: Yes. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
16 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JNJ-64251330 in people with Adenomatous Polyposis Coli, run by Janssen Research & Development, LLC at 16 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, South Korea, France, Spain, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change from Baseline in Colorectal Polyp Burden for all Polyps at Week 24 (time frame: Baseline and Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2023.