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A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis

Primary Purpose

Adenomatous Polyposis Coli

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JNJ-64251330
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenomatous Polyposis Coli

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • City of Hope
  • University of Miami
  • Massachusetts General Hospital
  • Dana Farber Cancer Institute
  • University of Texas MD Anderson Cancer Center
  • Hopital Edouard Herriot - CHU Lyon
  • APHM Hopital Timone
  • Universitatsklinikum Bonn
  • Seoul National University Hospital
  • Severance Hospital, Yonsei University Health System
  • Asan Medical Center
  • Samsung Medical Center
  • Academisch Medisch Centrum Universiteit van Amsterdam
  • Pan American Center for Oncology Trials LLC
  • Hosp. Clinic I Provincial de Barcelona
  • Clinica Univ. de Navarra

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

JNJ-64251330

Arm Description

Participants will receive oral dose of JNJ-64251330 twice daily for 24 Weeks.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Percentage Change in Number of Colon Polyps
Percentage change in number of colon polyps will be reported.
Percentage Change in Number of Rectal Polyps
Percentage change in number of rectal polyps will be reported.
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.
Percentage Change in Number of Duodenal Polyps
Percentage change in number of duodenal polyps will be reported.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.

Full Information

First Posted
August 13, 2021
Last Updated
June 1, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05014360
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
November 10, 2021 (Actual)
Primary Completion Date
February 15, 2023 (Actual)
Study Completion Date
February 15, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenomatous Polyposis Coli

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
JNJ-64251330
Arm Type
Experimental
Arm Description
Participants will receive oral dose of JNJ-64251330 twice daily for 24 Weeks.
Intervention Type
Drug
Intervention Name(s)
JNJ-64251330
Other Intervention Name(s)
Lorpucitinib
Intervention Description
JNJ-64251330 tablets will be administered orally.
Primary Outcome Measure Information:
Title
Percentage Change from Baseline in Colorectal Polyp Burden for all Polyps at Week 24
Description
Percentage change from baseline in colorectal polyp burden for all polyps (the sum of the polyp diameters) at Week 24 will be reported.
Time Frame
Baseline and Week 24
Title
Percentage Change from Baseline in Colorectal Polyp Burden for Polyps >=2 mm at Week 24
Description
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.
Time Frame
Baseline and Week 24
Secondary Outcome Measure Information:
Title
Percentage Change in Number of Colon Polyps
Description
Percentage change in number of colon polyps will be reported.
Time Frame
Baseline and Week 24
Title
Percentage Change in Number of Rectal Polyps
Description
Percentage change in number of rectal polyps will be reported.
Time Frame
Baseline and Week 24
Title
Percentage Change in Number of J-pouch Polyps
Description
Percentage change in number of J-pouch polyps (for participants with an ileal pouch-anal anastomosis [IPAA]) will be reported.
Time Frame
Baseline and Week 24
Title
Percentage Change in Number of Duodenal Polyps
Description
Percentage change in number of duodenal polyps will be reported.
Time Frame
Baseline and Week 24
Title
Percentage Change in Colon Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Description
Percentage change in colon polyp burden for all polyps, polyps >=2 mm and polyps >=5 mm will be reported.
Time Frame
Baseline and Week 24
Title
Percentage Change in Rectal Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Description
Percentage change in rectal polyp burden for all polyps, polyps >=2 mm and polyps >=5 mm will be reported.
Time Frame
Baseline and Week 24
Title
Percentage Change in J-Pouch Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Description
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.
Time Frame
Baseline and Week 24
Title
Percentage Change in Duodenal Polyp Burden for all Polyps, Polyps >=2 mm and Polyps >=5 mm
Description
Percentage change in duodenal polyp burden for all polyps, polyps >=2 mm and polyps >=5 mm will be reported.
Time Frame
Baseline and Week 24
Title
Change in International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Polyposis Stage (with and Without Colon)
Description
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.
Time Frame
Baseline and Week 24
Title
Change in Spigelman Stage Score
Description
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.
Time Frame
Baseline and Week 24
Title
Number of Participants with Adverse Events (AEs)
Description
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.
Time Frame
Up to 32 weeks
Title
Number of Participants with AEs by Severity
Description
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.
Time Frame
Up to 32 weeks
Title
Plasma Concentration of JNJ-64251330 Over Time
Description
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).
Time Frame
Up to Week 24
Title
Tissue Concentration of JNJ-64251330 Over Time
Description
Tissue biopsy samples will be analyzed to determine tissue concentrations of JNJ-64251330 using a validated specific, and sensitive LC-MS/MS.
Time Frame
Up to Week 24
Title
Levels of JAK/STAT Pathway Signaling Effector Proteins including pSTAT-3 Relative to Baseline Levels in Colorectal Polyps
Description
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.
Time Frame
Up to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hopital Edouard Herriot - CHU Lyon
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
APHM Hopital Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Universitatsklinikum Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Academisch Medisch Centrum Universiteit van Amsterdam
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Pan American Center for Oncology Trials LLC
City
Río Piedras
ZIP/Postal Code
00 935
Country
Puerto Rico
Facility Name
Hosp. Clinic I Provincial de Barcelona
City
Madrid
ZIP/Postal Code
8036
Country
Spain
Facility Name
Clinica Univ. de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis

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