LB: CIFFREO, a phase 3, randomized, double-blind, placebo-controlled study of fordadistrogene movaparvovec in Duchenne muscular dystrophy (DMD)

Topic:

Clinical Trials

Poster Number: T427

Author(s):

Eugenio Mercuri, MD, Fondazione Policlinico Universitario A Gemelli, Andres Nascimento, MD, San Joan de Deu Barcelona, Jin-Hong Shin, MD, Pusan National University Yangsan Hospital, Yangsan, South Korea, George M Stettner, MD, University Children’s Hospital Zurich, Zürich, Switzerland, Michela Guglieri, Prof, John Walton Muscular Dystrophy Research, Newcastle University and Newcastle Hospitals NHS Foundatio, Aravindhan Veerapandiyan, MD, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U, Kasia Lobello, MD, Pfizer Inc, New York, NY, USA, Heliang Shi, PhD, Pfizer, Pamela Schwartz, MD, Pfizer Inc, New York, NY, USA, Silvina Gallo, MD, Pfizer Inc, New York, NY, USA, Qi Shen, MD, PhD, Pfizer, Inc., Daniel Levy, MD, Pfizer Inc, New York, NY, USA, Francesco Muntoni, MD, Great Ormond Street Institute of Child Health

Background: Fordadistrogene movaparvovec (FM) (PF-06939926) is a recombinant AAV9-based gene therapy in development for DMD. We present the study design and demographic data of enrolled participants in CIFFREO. Study Design and Methods: CIFFREO is an ongoing, phase 3, multicenter, placebo-controlled, double-blind study to assess the safety and efficacy of FM in DMD participants. Ambulatory participants aged ≥4 – <8 years with a confirmed genetic diagnosis of DMD, North Star Ambulatory Assessment (NSAA) total score >16 and <30, and on daily steroids for ≥3 months before screening are included. Key exclusion criteria are any mutations affecting any exons between 9-13 inclusive, deletions affecting exons 29 and 30, or deletions affecting any exons between 56-71 inclusive, cardiac pathology, prior gene therapy treatment, and neutralizing antibodies to AAV9. Eligible participants were randomized 2:1 to a single infusion of FM (2E14 vg/kg) or placebo at Year 1 and placebo or FM at Year 2. The primary endpoint is change from baseline (CFB) at Week 52 in the NSAA total score. Secondary endpoints include mini-dystrophin expression and distribution, serum creatine kinase concentration, characterization of skills assessed based on NSAA individual items, CFB in 10-meter run/walk velocity, rise from floor velocity, and Modified Pediatric Outcomes Data Collection Instrument measures. The study will also explore movement data collected using actigraphy. Safety endpoints are the incidence and severity of treatment-emergent adverse events (AEs), serious AEs, abnormal laboratory findings, clinically relevant changes in physical and neurological exams, ECGs and cardiac images. Forty-two sites across Asia, Australasia, Eastern Europe, Middle East, North America, and Western Europe are participating. Results: The full analysis set comprises 107 randomized and dosed participants. At screening, mean (SD) age was 5.9 (1.2) years; 45 participants were aged <6 years and 62 were aged ≥6 years. NSAA total score was 23.1 (3.8). Conclusions: CIFFREO aims to compare the safety and efficacy of FM with placebo in participants with DMD. ClinicalTrials.gov: NCT04281485