Duchenne Muscular Dystrophy (DMD)
Conditions
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)
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).
Interventions
DRUGIV infusion
IV infusion
OTHERPlacebo
IV infusion
Sponsors
PepGen Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
6 Years to 16 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Plasma pharmacokinetic (PK) parameters (MAD period) | Baseline to Week 28 | Maximum observed plasma concentration of PGN-EDO51 |
| Skeletal muscle concentration of PGN-EDO51 (MAD period) | Baseline to Week 28 | Change from baseline in skeletal muscle concentration of PGN-EDO51 after multiple doses |
| Plasma pharmacokinetic (PK) parameters (LTE period) | Baseline to Week 104 | PK sampling for PGN-EDO51 and PGN-PMO51 plasma levels |
Outcome results
None listed