A Study of Guselkumab in Participants With Familial Adenomatous Polyposis

January 31, 2025 updated by: Janssen Research & Development, LLC

A Phase 1b, Multicenter, Randomized, Blinded, Placebo-controlled Study to Evaluate the Efficacy of Guselkumab in Subjects With Familial Adenomatous Polyposis

The purpose of this study is to determine the effect of treatment with guselkumab in participants with familial adenomatous polyposis (FAP) on rectal/pouch polyp burden.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Familial adenomatous polyposis (FAP) is the most common polyposis syndrome. It is autosomal dominant inherited disorder characterized by early onset of hundreds to thousands of adenomatous polyps throughout colon. If left untreated, this syndrome may develop colorectal cancer (CRC). Polyps from individuals with FAP display inflammatory features associated with activation of interleukin (IL) 23/IL 17/JAK/STAT3 pathway. This inflammation is thought to contribute to further mutagenesis, culminating in tumor development. Specifically, IL-23 is linked to tumor growth and progression in CRC. Guselkumab is a human immunoglobulin monoclonal antibody directed against p19 subunit of IL-23, specifically targets IL-23 and inhibits its interaction with IL-23 receptor, inhibiting IL 23 specific intracellular signaling and subsequent cell activation and cytokine production, which result in less inflammation and reduce tumor development. The clinical hypothesis of this study is that treatment with guselkumab will reduce rectal/pouch polyp burden compared with baseline in active arms compared with placebo. The study is designed to determine if guselkumab has clinical activity in colorectum and duodenum, by reducing number of polyps over a period of 24 weeks. Participants will be randomized to 1 of 3 treatment arms (Guselkumab 100 mg [milligram] SC [subcutaneous], Guselkumab 300 mg SC, and placebo SC). Efficacy evaluations include rectal/pouch polyp burden assessment, biomarker analysis include discrete IL-23 signaling effector proteins (IL-23R, pSTAT3, Il-17A) and safety evaluations will include monitoring of adverse events, laboratory tests, vital sign measurements, and physical examination. Safety will be monitored throughout study (up to Week 60).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
77

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon, France, 69437
        • Hopital Edouard Herriot - CHU Lyon
      • Marseille, France, 13385
        • APHM Hopital Timone
  • Germany
      • Bonn, Germany, 53127
        • Universitätsklinikum Bonn
      • Ulm, Germany, 89070
        • Universitätsklinikum Ulm
  • Israel
      • Tel Aviv, Israel, 64239
        • Sourasky MC
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Academisch Medisch Centrum Universiteit van Amsterdam
      • Leiden, Netherlands, 2333 ZA
        • Leiden University Medical Center
      • Rotterdam, Netherlands, 3015 GD
        • Erasmus MC
  • Poland
      • Poznan, Poland, 60 355
        • Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Po
      • Warszawa, Poland, 02-781
        • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
  • Puerto Rico
      • Rio Piedras, Puerto Rico, 00935
        • Pan American Center for Oncology Trials LLC
  • Spain
      • Barcelona, Spain, 8036
        • Hosp Clinic de Barcelona
      • Barcelona, Spain, 8035
        • Hosp Univ Vall D Hebron
  • Sweden
      • Stockholm, Sweden, 171 76
        • Karolinska Universitetssjukhuset
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • California
      • Duarte, California, United States, 91010
        • City of Hope
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale University
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Jacksonville
      • Miami, Florida, United States, 33136
        • University of Miami
      • Tampa, Florida, United States, 33606
        • University of South Florida
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center Columbia University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Columbus, Ohio, United States, 43210
        • Wexner Medical Center at the Ohio State University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania - Perelman School of Medicine
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Huntsman Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Phenotypic familial adenomatous polyposis (FAP) with disease involvement of the colorectum by either genetic or clinical diagnosis: Adenomatous polyposis coli (APC) germline mutation with or without family history, or with greater than (>)100 adenomas in large intestine and a family history of FAP, attenuated FAP is allowed. FAP phenotype post colectomy for polyposis with a family history of FAP may be allowed
  • Post-colectomy or subtotal colectomy
  • Polyps with a sum of diameters greater than or equal to (>=)10 millimeter (mm) in the rectum or pouch on biopsy at screening
  • A woman of childbearing potential must agree not to get pregnant during the study and at least 12 weeks after the last dose of study administration
  • A woman must agree not to breast feed or donate eggs (ova, oocytes) during the study and for a period of 12 weeks after the last administration of study drug

Exclusion Criteria:

  • Prior use of any biologic therapy targeting interleukin (IL)-12/23, IL-17, or IL-23 receptor
  • Use of non-steroidal anti-inflammatory drugs other than aspirin during the study. The use 100 milligram (mg) of aspirin a day or 700 mg of aspirin per week is allowed
  • Treatment with other FAP-directed drug therapy (including NSAID [Nonsteroidal anti-inflammatory drug] drugs), unless completes a 4-week washout period prior to randomization
  • High grade dysplasia or cancer on biopsy at screening in GI tract (including stomach, duodenum, and colon/rectum/pouch)
  • Duodenal, colorectal, or pouch polyp: >2 centimeter (cm) unless excised at the screening evaluation; and 1 to 2 cm with evidence of high-grade dysplasia upon biopsy unless excised

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Guselkumab Dose 1
Participants will receive guselkumab Dose 1 subcutaneous (SC), 6 doses every 4 weeks from Week 0 to Week 20. Participants who respond to guselkumab may continue treatment at the same dose level through Week 48.
Drug: Guselkumab
Guselkumab SC will be administered every 4 weeks.
Other Names:
  • Tremfya
Experimental: Guselkumab Dose 2
Participants will receive guselkumab Dose 2 SC, 6 doses every 4 weeks from Week 0 to Week 20. Participants who respond to guselkumab may continue treatment at the same dose level through Week 48.
Drug: Guselkumab
Guselkumab SC will be administered every 4 weeks.
Other Names:
  • Tremfya
Placebo Comparator: Placebo
Participants will receive placebo SC, 6 doses every 4 weeks from Week 0 to Week 20.
Drug: Placebo
Placebo SC will be administered every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage Change from Baseline in Rectal/pouch Polyp Burden at Week 24
Time Frame: Baseline, Week 24
Percentage change from baseline in rectal/pouch polyp burden (sum of the polyp diameters) at Week 24 will be determined through endoscopy.
Baseline, Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage Change from Baseline in Number of Colorectal Polyps
Time Frame: Baseline, Weeks 24 and 52
Percentage change from baseline in number of colorectal polyps will be determined.
Baseline, Weeks 24 and 52
Percentage Change from Baseline in Number of J-pouch Polyps
Time Frame: Baseline, Weeks 24 and 52
Percentage change from baseline in number of J-pouch polyps will be determined.
Baseline, Weeks 24 and 52
Percentage Change from Baseline in J-pouch Polyp Burden
Time Frame: Baseline, Weeks 24 and 52
Percentage change from baseline in J-pouch polyp burden (sum of polyp diameters) will be determined.
Baseline, Weeks 24 and 52
Percentage Change from Baseline in Number of Duodenal Polyps
Time Frame: Baseline, Weeks 24 and 52
Percentage change from baseline in number of duodenal polyps will be determined.
Baseline, Weeks 24 and 52
Percentage Change from Baseline in Duodenal Polyp Burden
Time Frame: Baseline, Weeks 24 and 52
Percentage change from baseline in duodenal polyp burden (sum of polyp diameters) will be determined.
Baseline, Weeks 24 and 52
Change in International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Stage
Time Frame: Baseline, Weeks 24 and 52
Change in InSiGHT stage will be determined. Various stages of InSiGHT staging system are defined as: Stage 0: 0-10 polyps, all less than (<)5 millimeter (mm); Stage 1: 10-25 polyps, most < 5 mm, none greater than (>) 1 centimeter (cm); Stage 2: 10-25 polyps, any > 1 cm, 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; and Stage 4: > 25 polyps amenable to complete removal, or any incompletely excised sessile polyp showing HGD, any invasive cancer).
Baseline, Weeks 24 and 52
Change in Spigelman Stage Score
Time Frame: Baseline, Weeks 24 and 52
Change in Spigelman stage score will be determined. 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. Points are accumulated for polyps' number, size, histology and severity of dysplasia. Stage 1 indicates mild disease, whereas stage 3-4 indicates severe duodenal polyposis.
Baseline, Weeks 24 and 52
Trough Concentration of Guselkumab
Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Serum samples will be analyzed to determine trough concentrations of guselkumab using a validated specific, and sensitive method.
Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Number of Participants with Anti-guselkumab Antibodies
Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Number of participants with Anti-guselkumab antibodies will be determined.
Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Anti-guselkumab Antibodies Serum Titers
Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed positive samples will be reported.
Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Number of Participants with Adverse Events as a Measure of Safety
Time Frame: From Screening up to 60 Weeks
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
From Screening up to 60 Weeks
Number of Participants with Vital Sign Abnormalities as a Measure of Safety and Tolerability
Time Frame: From Screening up to 52 Weeks
Number of participants with vital sign abnormalities will be reported. Vital signs includes temperature, pulse/heart rate, respiratory rate and blood pressure.
From Screening up to 52 Weeks
Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability
Time Frame: From Screening up to 52 Weeks
Number of participants with clinical laboratory abnormalities will be reported. Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.
From Screening up to 52 Weeks
Relative Changes to Baseline in Levels of Interleukin (IL)-23 Effector Proteins in Biopsy Tissue
Time Frame: Baseline, Weeks 12, 24, and 52
Relative Changes to Baseline in levels of IL-23 effector proteins in biopsy tissue will be measured.
Baseline, Weeks 12, 24, and 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Research & Development, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 19, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 13, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 23, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 27, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 28, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR108515
  • CNTO1959COR1001 (Other Identifier: Janssen Research & Development, LLC)
  • 2019-001980-57 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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