Clinical trial NCT06833931: A Study of PGN-EDO51 or Placebo in People With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment
Official 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)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy (DMD)
Keywords: Enhanced Delivery Oligonucleotide
Peptide-conjugated phosphorodiamidate
Morpholino oligomer
Oligonucleotide
Exon 51
Next-generation oligonucleotide
Cell-penetrating peptide
Muscular Dystrophies
Neuromuscular Disease
Dystrophin production
Splice correcting oligonucleotide
Endosomal Escape
Delivery to the cell nucleus
Antisense oligonucleotide
phosphorodiamidate morpholino oligomer (PPMO)
Lead sponsor: PepGen Inc
Sponsor class: INDUSTRY
First posted: 2025-02-19
Enrollment: 16
Sex: MALE
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Adverse events and serious adverse events (safety and tolerability of PGN-EDO51 during the MAD period)
timeFrame: Signing of informed consent to Week 28
measure: Dystrophin levels (MAD period)
timeFrame: Baseline to Week 28
measure: Adverse events and serious adverse events (safety and tolerability of PGN-EDO51 during the LTE period)
timeFrame: Signing of informed consent to Week 108
Secondary outcomes:
measure: Plasma pharmacokinetic (PK) parameters (MAD period)
timeFrame: Baseline to Week 28
measure: Plasma pharmacokinetic (PK) parameters (MAD period)
timeFrame: Baseline to Week 28
measure: Plasma pharmacokinetic (PK) parameters (MAD period)
timeFrame: Baseline to Week 28
measure: Plasma pharmacokinetic (PK) parameters (MAD period)
timeFrame: Baseline to Week 28
measure: Skeletal muscle concentration of PGN-EDO51 (MAD period)
timeFrame: Baseline to Week 28
measure: Plasma pharmacokinetic (PK) parameters (LTE period)
timeFrame: Baseline to Week 104
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford Children's Hospital
Study officials:
References: