NCT03649971

A Study of Guselkumab in Participants With Familial Adenomatous Polyposis

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 77 (actual)
• Sponsor: Janssen Research & Development, LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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).

Conditions

• Adenomatous Polyposis Coli

Interventions

Type	Name	Description
DRUG	Guselkumab	Guselkumab SC will be administered every 4 weeks.
DRUG	Placebo	Placebo SC will be administered every 4 weeks.

Timeline

• Start date: 2018-11-19
• Primary completion: 2021-09-13
• Completion: 2022-03-23
• First posted: 2018-08-28
• Last updated: 2025-02-03

Locations

32 sites across 9 countries: United States, France, Germany, Israel, Netherlands, Poland, Puerto Rico, Spain, Sweden

Regulatory

• FDA-regulated drug study