Highlights From the 15th Annual Congress of EAHAD
Dose Selection and Study Design for B-LIEVE, A Phase 1/2 Dose Confirmation Clinical Trial of FLT180A Gene Therapy for Patients with Hemophilia B
G.Young1,P.Chowdary, 2,3,S.Barton4, A.Long4
1Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, United States;2 Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital;3 University College London,United Kingdom;4 Freeline, Stevenage, United Kingdom
Key Data Points
The B-LIEVE study is a phase 1/2 study of commercially manufactured FLT180a designed to confirm a target dose for a phase 3 study. The starting dose for B-LIEVE was based on results from the B-AMAZE trial, which demonstrated that FIX levels at Day 21 following infusion were highly predictive of FIX levels at Day 182 (week 26). An Emax dose-response model indicated that a dose of 7.7 x 1011 vg/kg should produce a mean FIX level of 67% of normal at Day 21 corresponding to a mean FIX level of 115% of normal at Day 182.
The adaptive study design for B-LIEVE includes a starting FLT180a dose of 7.7 x 1011 vg/kg in 3 participants. The starting dose will be adjusted in subsequent cohorts of 3 participants, each based on the Day 21 FIX levels in the previous cohort. Up to 9 participants (3 cohorts) will be enrolled with a 52-week follow-up period in order to confirm a dose for a phase 3 study.
Presented by Daniel Hart, BSc, MBChB, MRCP, FRCPath, PhD and Johnny Mahlangu, BSc, MBBCh, MMed, FCPath
Presented by Daniel Hart, BSc, MBChB, MRCP, FRCPath, PhD and Wolfgang A. Miesbach, MD, PhD
Presented by Daniel Hart, BSc, MBChB, MRCP, FRCPath, PhD and Declan Noone
Presented by Daniel Hart, BSc, MBChB, MRCP, FRCPath, PhD and Maria Elisa Mancuso, MD, PhD