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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03649971
Other study ID # CR108515
Secondary ID CNTO1959COR10012
Status Completed
Phase Phase 1
First received
Last updated
Start date November 19, 2018
Est. completion date March 23, 2022

Study information

Verified date June 2023
Source Janssen Research & Development, LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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).


Recruitment information / eligibility

Status Completed
Enrollment 77
Est. completion date March 23, 2022
Est. primary completion date September 13, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
Guselkumab
Guselkumab SC will be administered every 4 weeks.
Placebo
Placebo SC will be administered every 4 weeks.

Locations

Country Name City State
France Hopital Edouard Herriot - CHU Lyon Lyon
France APHM Hopital Timone Marseille
Germany Universitatsklinikum Bonn Bonn
Germany Universitätsklinikum Ulm Ulm
Israel Sourasky MC Tel Aviv
Netherlands Academisch Medisch Centrum Universiteit van Amsterdam Amsterdam
Netherlands Leiden University Medical Center Leiden
Netherlands Erasmus MC Rotterdam
Poland Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Po Poznan
Poland Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa
Puerto Rico Pan American Center for Oncology Trials LLC Río Piedras
Spain Hosp. Univ. Vall D Hebron Barcelona
Spain Hosp. Clinic I Provincial de Barcelona Madrid
Sweden Karolinska Universitetssjukhuset Stockholm
United States Dana Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States Cleveland Clinic Cleveland Ohio
United States Wexner Medical Center at the Ohio State University Columbus Ohio
United States City of Hope Duarte California
United States University of Texas MD Anderson Cancer Center Houston Texas
United States Mayo Clinic Jacksonville Jacksonville Florida
United States University of Miami Miami Florida
United States Yale University New Haven Connecticut
United States Ochsner Medical Center New Orleans Louisiana
United States Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center New York New York
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States University of Pennsylvania - Perelman School of Medicine Philadelphia Pennsylvania
United States Mayo Clinic Phoenix Arizona
United States Washington University School of Medicine Saint Louis Missouri
United States University of Utah Huntsman Cancer Institute Salt Lake City Utah
United States University of Washington Seattle Washington
United States University of South Florida Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel,  Netherlands,  Poland,  Puerto Rico,  Spain,  Sweden, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage Change from Baseline in Rectal/pouch Polyp Burden at 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 Percentage Change from Baseline in Number of Colorectal Polyps Percentage change from baseline in number of colorectal polyps will be determined. Baseline, Weeks 24 and 52
Secondary Percentage Change from Baseline in Number of J-pouch Polyps Percentage change from baseline in number of J-pouch polyps will be determined. Baseline, Weeks 24 and 52
Secondary Percentage Change from Baseline in J-pouch Polyp Burden Percentage change from baseline in J-pouch polyp burden (sum of polyp diameters) will be determined. Baseline, Weeks 24 and 52
Secondary Percentage Change from Baseline in Number of Duodenal Polyps Percentage change from baseline in number of duodenal polyps will be determined. Baseline, Weeks 24 and 52
Secondary Percentage Change from Baseline in Duodenal Polyp Burden Percentage change from baseline in duodenal polyp burden (sum of polyp diameters) will be determined. Baseline, Weeks 24 and 52
Secondary Change in International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Stage 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
Secondary Change in Spigelman Stage Score 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
Secondary Trough Concentration of Guselkumab 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
Secondary Number of Participants with Anti-guselkumab Antibodies Number of participants with Anti-guselkumab antibodies will be determined. Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48
Secondary Anti-guselkumab Antibodies Serum Titers 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
Secondary Number of Participants with Adverse Events as a Measure of Safety 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
Secondary Number of Participants with Vital Sign Abnormalities as a Measure of Safety and Tolerability 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
Secondary Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability 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
Secondary Relative Changes to Baseline in Levels of Interleukin (IL)-23 Effector Proteins in Biopsy Tissue Relative Changes to Baseline in levels of IL-23 effector proteins in biopsy tissue will be measured. Baseline, Weeks 12, 24, and 52
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