A Study of Guselkumab in Participants With Familial Adenomatous Polyposis

Official Title

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

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.

Trial Description

Primary Outcome:

• Percentage Change from Baseline in Rectal/pouch Polyp Burden at Week 24

Secondary Outcome:

• Percentage Change from Baseline in Number of Colorectal Polyps
• Percentage Change from Baseline in Number of J-pouch Polyps
• Percentage Change from Baseline in J-pouch Polyp Burden
• Percentage Change from Baseline in Number of Duodenal Polyps
• Percentage Change from Baseline in Duodenal Polyp Burden
• Change in International Society for Gastrointestinal Hereditary Tumours (InSiGHT) Stage
• Change in Spigelman Stage Score
• Trough Concentration of Guselkumab
• Number of Participants with Anti-guselkumab Antibodies
• Anti-guselkumab Antibodies Serum Titers
• Number of Participants with Adverse Events as a Measure of Safety
• Number of Participants with Vital Sign Abnormalities as a Measure of Safety and Tolerability
• Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability
• Relative Changes to Baseline in Levels of Interleukin (IL)-23 Effector Proteins in Biopsy Tissue

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 tumour development. Specifically, IL-23 is linked to tumour 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 tumour 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).

View this trial on ClinicalTrials.gov