A Phase 3, Multi-Site, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of eRapa to Improve Clinical Outcomes in Patients With Familial Adenomatous Polyposis

Summary

The main goal of this clinical trial is to learn if the drug eRapa works to slow down the progression of disease in patients diagnosed with Familial Adenomatous Polyposis (FAP). Researchers will compare eRapa to Placebo. The questions to be answered by this trial are: * Does taking eRapa help to slow down the progression of the disease in patients with FAP? * Is eRapa a safe treatment for patients diagnosed with FAP? * What is the effect of eRapa on the number of polyps found in GI tract of patients diagnosed with FAP? * How does treatment with eRapa affect a patient's quality of life? Participants will: * Take eRapa or placebo once per day every other week until disease progresses (gets worse), stops taking part in the trial or dies. * Visit the clinic once every 3 months for check ups and tests. * Have an endoscopy at the start of the trial and then every 6 months to check on whether the disease is getting better or worse.

Detailed description

This is a Phase 3, multi-site, prospective, randomized, double-blind, placebo-controlled trial of eRapa administered to patients with FAP who are at high risk of disease progression. 168 patients with FAP will be enrolled in the trial and randomized 2:1 to receive 0.5 mg eRapa or matching placebo orally, once a day (QD) every other week. There is no minimum treatment duration as this is an event-driven trial; however, the intervention period will continue until disease progression, participant withdrawal from treatment, or until the overall trial endpoint is reached. Participant eligibility is restricted to patients under active surveillance for genetic or clinically diagnosed FAP and who have an intact colon; who are postcolectomy/subtotal colectomy and have documented residual polyps in the rectum/sigmoid or who are post-proctocolectomy with ileal-pouch anal anastomosis and documented polyps in the pouch. Eligible participants will undergo a baseline endoscopy and subsequent endoscopic procedures performed every 6 months to monitor for disease progression. Randomized patients will be stratified based on the following disease characteristics: * Intact colon versus post-surgical resection with retained rectum/sigmoid or pouch, and * Duodenal polyposis (current Spigelman stage score ≤2 versus Spigelman stage score ≥3) For the purposes of this trial, high-risk for disease progression is defined as meeting one of the following: * Patients who have intact colons and have \>100 polyps but ≤500 polyps * Patients who have retained rectum/sigmoid or ileal-pouch-anal anastomosis and have ≥10 polyps that are ≥3 mm in diameter, or * Patients who have a history of duodenal polyposis Spigelman stage score of 3 or 4 with at least 1 duodenal polyp that has been removed within 18 months of screening. Trial assessments should be conducted as per the Schedule of Activities with a visit occurring about once every 3 months. Assessment of Spigelman stage will not require a biopsy unless the lesion has an abnormal appearance and/or is ≥10 mm.

Arms & interventions

• DrugeRapa (encapsulated rapamycin)

  0.5 mg capsules for oral use; white opaque capsule filled with off-white powder; Trial intervention will be provided in 28-count round high-density polyethylene bottles with a polypropylene child-resistant screw cap and foil induction seal.

• DrugPlacebo

  Capsules in 28-count round high-density polyethylene bottles with a polypropylene child-resistant screw cap and foil induction seal.

Outcome measures

Eligibility criteria