CONNECT2-EDO51
Research type
Research Study
Full title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study of PGN-EDO51 with a Long-Term Extension in Participants with Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment (CONNECT2-EDO51).
IRAS ID
1008517
Contact name
Hayley Parker
Contact email
Sponsor organisation
PepGen Inc.
Clinicaltrials.gov Identifier
Research summary
Research Summary
Duchenne muscular dystrophy (DMD) is a rare, genetic disorder affecting a protein inside muscle cells called “dystrophin”. The dystrophin gene is mutated in people with DMD, resulting in virtually no dystrophin protein production which causes muscle cells to be fragile and easily damaged. This leads to progressive muscle breakdown and muscle weakness, which progresses with age and leads to the loss of ambulation before adolescence and, without treatment life expectancy is reduced. In some individuals with DMD, the mutations are such that skipping over a part of the gene named “exon 51” (part of the instructions for a cell to make dystrophin) can allow the cell to produce a shorter, but functional dystrophin protein. The investigational medicine called PGN-EDO51 is an exon 51 skipping therapy designed to make functional (but shorter) dystrophin protein which may slow the progression of DMD.
The purpose of this study is to learn about the safety and tolerability of PGN-EDO51 in males with DMD and to measure the levels of dystrophin protein in skeletal muscle after multiple doses. Participants must be males, aged 6 years and above and meet the eligibility criteria.
The first part of the study is double-blind, placebo-controlled, and multiple-ascending dose (MAD). Approximately 24 eligible participants will be enrolled into 3 cohorts and will receive multiple doses of the study drug: PGN-EDO51 or placebo, every 4 weeks for 24 weeks with a follow-up visit at the end of the MAD part at week 28. The participant will have a 3 in 4 (75%) chance of receiving PGN-EDO51.
Participants who complete the MAD part of the study will have the option to participate in the open-label long-term extension (LTE) part of the study in which all enrolled participants will receive PGN-EDO51 every 4 weeks via an IV injection for up to 104 weeks with an end-of-study visit at week 108. This is a multicentre, global study with plans to be run in sites in Europe, the UK and US.
Summary of Results
What Was the Study About?
The study was called PGN-EDO51-103 (short name CONNECT2) and was testing a new medicine called PGN-EDO51 to help boys with a muscle disease called Duchenne Muscular Dystrophy (DMD). This disease makes muscles weaker over time. The medicine was developed to help boys who had a type of DMD that can be treated by skipping part of the DMD gene that causes this disease (called exon 51 skipping).
How Was the Study Planned?
The study was designed to test the medicine in two parts:
Part 1 (Multiple Ascending Dose-MAD): Part 1 was split into 2 halves. In the first half, 6 boys would receive the medicine at doses that are equal to 10 mg per kilogram of body weight (mg/kg) and 2 would receive a fake medicine (called a placebo). In the second half, another 6 boys would receive the medicine at 12 mg/kg with 2 more boys receiving placebo.
Part 2: Boys who finished part 1 of the study could enter another, longer study (called an open-label extension) where everyone would receive PGN-EDO51.
The medicine and the placebo were given through a needle into a vein (IV infusion). The study was being run to see if the medicine was safe, how it moved through the body, and if it helped make the muscle protein called dystrophin, which is low in the boys with the disease.
What Happened in the Study?
Only 2 boys signed up for the study, but none got the medicine. The company stopped the study early because another similar study showed the medicine didn’t make enough of the muscle
REC name
Wales REC 3
REC reference
24/WA/0011
Date of REC Opinion
6 Feb 2024
REC opinion
Further Information Favourable Opinion