A Study of PGN-EDO51 or Placebo in People With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment (CONNECT2-EDO51)

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)

The study consists of 3 periods: A Screening Period (up to 45 days), a double-blind, placebo-controlled Multiple Ascending Dose (MAD) Period (28 weeks), and a Long-Term Extension (LTE) Period (108 weeks).

The primary purpose of the MAD period is to evaluate the safety and tolerability and levels of dystrophin after multiple ascending intravenous (IV) doses of PGN-EDO51 administered to participants with Duchenne muscular dystrophy (DMD). During the MAD period, participants will be randomized to either receive PGN-EDO51 or placebo in a 3:1 fashion, meaning that participants have a 75% chance of receiving PGN-EDO51 and a 25% chance of receiving placebo during this period. The primary purpose of the open-label LTE period is to evaluate the long-term safety and tolerability of PGN-EDO51 in participants who have completed the MAD period. All participants who roll-over into the LTE will receive PGN-EDO51 (no placebo in the LTE).

Study Overview

• Status: Withdrawn
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Other: Placebo; Drug: IV infusion

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom
    • Leeds Teaching Hospital NHS Trust
  • Oxford, United Kingdom
    • Oxford Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of DMD with a genetic alteration that can be treated by skipping exon 51
• Body weight at least 25kg (55lbs)
• Performance of Upper Limb (PUL) 2.0 entry score of at least 4

Exclusion Criteria:

• Known history or presence of any clinically significant conditions that may interfere with study safety assessments
• Treatment with any gene replacement therapy for the treatment of DMD at any time
• Current or recent systemic infection within 2 weeks prior to Screening or infection requiring IV antibiotics within 4 weeks prior to Screening
• Recent surgery requiring anesthesia within 3 months prior to Screening or expected surgery requiring general anesthesia during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PGN-EDO51 at Dose Level 1 or Placebo every 4 weeks	Other: Placebo; IV infusion; Drug: IV infusion; IV infusion
Experimental: PGN-EDO51 at Dose Level 2 or Placebo every 4 weeks	Other: Placebo; IV infusion; Drug: IV infusion; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events and serious adverse events (safety and tolerability of PGN-EDO51 during the MAD period)	Signing of informed consent to Week 28
Dystrophin levels (MAD period)	Baseline to Week 28
Adverse events and serious adverse events (safety and tolerability of PGN-EDO51 during the LTE period)	Signing of informed consent to Week 108

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetic (PK) parameters (MAD period)	Maximum observed plasma concentration of PGN-EDO51	Baseline to Week 28
Plasma pharmacokinetic (PK) parameters (MAD period)	Time to maximum observed plasma concentration of PGN-EDO51	Baseline to Week 28
Plasma pharmacokinetic (PK) parameters (MAD period)	Apparent terminal half-life of PGN-EDO51	Baseline to Week 28
Plasma pharmacokinetic (PK) parameters (MAD period)	Area under the curve for concentration time of PGN-EDO51	Baseline to Week 28
Skeletal muscle concentration of PGN-EDO51 (MAD period)	Change from baseline in skeletal muscle concentration of PGN-EDO51 after multiple doses	Baseline to Week 28
Plasma pharmacokinetic (PK) parameters (LTE period)	PK sampling for PGN-EDO51 and PGN-PMO51 plasma levels	Baseline to Week 104

Collaborators and Investigators

• Sponsor: PepGen Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2024
• Primary Completion (Actual): May 28, 2025
• Study Completion (Actual): May 28, 2025

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): February 19, 2025

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Neuromuscular Disease; Oligonucleotide; Antisense oligonucleotide; Muscular Dystrophies; Exon 51; Enhanced Delivery Oligonucleotide; Peptide-conjugated phosphorodiamidate; Morpholino oligomer; Next-generation oligonucleotide; Cell-penetrating peptide; Dystrophin production; Splice correcting oligonucleotide; Endosomal Escape; Delivery to the cell nucleus; phosphorodiamidate morpholino oligomer (PPMO)
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: PGN-EDO51-103; U1111-1303-9370 (Other Identifier: WHO); 2023-508383-29-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No