AB0433 STUDY DESIGN FOR THE RANDOMISED CONTROLLED PHASE II ReSScue TRIAL: SAFETY AND EFFICACY OF FAECAL MICROBIOTA TRANSPLANTATION BY ANAEROBIC CULTIVATED HUMAN INTESTINAL MICROBIOME (ACHIM) IN PATIENTS WITH SYSTEMIC SCLEROSIS

Background:Gastro-intestinal tract (GIT) symptoms is highly prevalent in patients with systemic sclerosis (SSc). The GIT-symptoms impact on the quality of life is significant, and available treatment alternatives are limited. Recently published articles show associations between gut microbiota changes and GIT-symptoms in SSc. We, therefore, performed a successful feasibility trial on faecal microbiota transplantation (FMT) in SSc patients using the single-donor bacterial culture “Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)”. Based on the promising results from the feasibility trial, we aim to evaluate the safety and efficacy of FMT by ACHIM in SSc patients. (NCT04300426)Objectives:To design a clinical trial that explores the safety and efficacy of FMT in SSc patients.Methods:The ReSScue trial is a phase II, placebo-controlled, randomised 20-week, multicentre trial. The trial comprises three parts. In the induction phase (A1) lasting from week 0 to week 12, participants are randomised 1:1 to repeat infusions of 30 ml ACHIM or placebo at week 0 and 2 by gastro-duodenoscopy. In the maintenance phase (A2), all study participants will receive 30 ml ACHIM at week 12 and are followed continued blinded until week 20.For longer-term data on intervention effects and safety, the participant will be followed for a maximum extended monitoring period of 16 weeks (part B).The primary endpoint is change from baseline to week 12 in UCLA GIT scores on bloating or diarrhoea, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are changes in UCLA GIT scores (bloating, diarrhoea and total) and safety measures.Results:We aim to enrol 70 SSc patients based on the power calculations for the primary endpoint “change in worst symptom from baseline to week 12”, with a considered drop out rate of 10%. This number of patients is expected to give a power of 80% of detecting a change in mean (p=0.05, two-sided) of -5.0 (or higher) if the relating standard deviation is 0.70 or lower. The patient screening started in September 2020, and we expect the study to be completed in May 2022.Conclusion:The ReSScue-study is to our knowledge the first FMT-study in SSc. This trial will assess the safety and efficacy of FMT in SSc patients with lower GI-symptoms, possibly leading to a novel treatment approach in SSc patients.Disclosure of Interests:Håvard Fretheim Grant/research support from: Received travel bursaries from Actelion, and remuneration from Bayer., Imon Barua: None declared, Vikas Sarna: None declared, Maylen N Carstens: None declared, Oliver Distler Speakers bureau: Below, Consultant of: Below, Grant/research support from: OD has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx, Baecon Discovery, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Italfarmaco, iQone, Kymera, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Dinesh Khanna Consultant of: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences, Inc., Grant/research support from: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences, Inc., Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus, Forbius, Boehringer Ingelheim, Øyvind Midtvedt Shareholder of: Son of owner of ACHIM., Henriette Didriksen Speakers bureau: Travel bursary - GSK, Alvilde Dhainaut: None declared, Anna-Kristine H Halse: None declared, Gunnstein Bakland: None declared, Inge Christoffer Olsen: None declared, Maiju E Pesonen: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche., Grant/research support from: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche.