Summary: Celiac.com 07/04/2022 - The Food and Drug Administration (FDA) has issued a set of new guidelines for companies doing celiac disease drug trials. The agency noted that the guidance is intended only to provide clarity regarding existing requirements, and should be viewed solely as recommendations, unless they mention specific regulations or laws. The FDA directs sponsors of trials for clinical drugs to ensure the following regarding celiac disease patients on a gluten-free diet: Trial population Patients should undergo diagnostic esophagogastroduodenoscopy, with multiple biopsies to confirm celiac diagnosis. The biopsies should include one or two samples of the duodenal bulb and at least four samples of the distal duodenum. To avoid inclusion of patients whose symptoms are not celiac-related, patients should receive esophagogastroduodenoscopy screening with biopsy to ensure they meet histologic eligibility criteria at the time of trial enrollment. Patients should be symptomatic at baseline, based on enrollment criteria, to allow for evaluation of symptom improvement. Prior to trail enrollment and for the full duration, patients should follow to a strict gluten-free diet with input from trained dietitians. Trial design The FDA recommends using randomized, double-blind, placebo-controlled trial design. Before randomization of participants, sponsors should include a screening period to confirm histologic eligibility criteria, document clinical signs and symptoms, and train patients and/or providers in collecting clinical outcome assessment data. Trial duration and outcome assessments should be informed by the therapy goal, expected drug onset of action and the time frame in which clinical benefit is observable. The FDA recommends a placebo-controlled treatment period of at least 52 weeks for drugs intended for chronic use, with continued patient adherence to a gluten-free diet. Efficacy assessments for both clinical and histologic endpoints may be evaluated at week 24, and esophagogastroduodenoscopy with biopsy should be performed at week 52 to assess durability of response. Sponsors should make sure their patients follow a gluten-free diet for the complete treatment period. Efficacy and clinical outcome assessments Trails intended to support market approval should include coprimary endpoints to assess a drug’s effect on clinical signs, symptoms and related underlying mucosal condition. The FDA also recommends a pre-specified secondary endpoint to determine the number of patients who see improvement of clinical signs, symptoms and mucosal inflammation. Trial sponsors should seek FDA input early, when critical milestones are met, and throughout drug development. Sponsors should also identify disease and treatment burdens using patient input. To better assess symptom severity and event-related signs and symptoms, sponsors should ask patients to rate their worst experience and frequency of a specific sign or symptom over a 24-hour period. Statistical and safety considerations To be demonstrate efficacy, trial results should demonstrate statistical significance for both clinical and histological endpoints, and analyses should include all randomized patients. Sponsors should assess gluten-free diet adherence, which could alter efficacy data. Moreover, sponsors should talk with patients about the importance of following a strict gluten-free diet, since the benefit of the drug is still unknown. To assess the safety of drugs intended for long-term use, patients should be follow the intended market dosage for at least one year. The FDA recommends that sponsors include safety analyses to compare risk and confidence intervals in treatment groups. Read the full recommendations at FDA.gov
