Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy

A Multicenter, Phase 2, Open-Label Study Evaluating the Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of KER-065 administered to adult and pediatric ambulatory and nonambulatory male participants with Duchenne Muscular Dystrophy (DMD) on stable background therapy.

This is a Phase 2, multicenter, open-label study of KER-065.

The study will consist of 3 periods:

• Screening Period (up to 6 weeks)
• Treatment Period (48 weeks)
• Safety Follow-up Period (4 weeks)

Participants will be enrolled in parallel into 1 of 3 treatment cohorts:

• Cohort A1 (Late Ambulatory)
• Cohort A2 (Late Ambulatory)
• Cohort N1 (Early Nonambulatory)

Key Inclusion Criteria:

• Diagnosis of DMD, defined as the presence of phenotypic features at screening consistent with DMD AND documented mutation in the dystrophin gene consistent with the diagnosis of DMD using a clinically validated genetic test.
• Receiving a stable regimen of systemic CS (including, but not limited to, prednisone, prednisolone, deflazacort, or vamorolone) for at least 90 days before screening.
• Body weight of ≥ 25.0 kg.

Ambulatory Participants Only (Cohort A1 and A2):

• Ambulatory, defined as able to walk independently without assistive devices.
• Able to TTR in < 10 seconds.
• Has a NSAA score ≥ 15 points.
• Cohort 2 only: Documentation of a stable dose of an approved exon-skipping therapy.

Nonambulatory Participants Only (Cohort N1):

• Nonambulatory, characterized as being unable to ambulate for a minimum of 3 months before first dose with onset of nonambulatory status AND a NSAA walk score of 0 and inability to perform the 10MWR.
• PUL v2.0 entry item score of 3 to 5, inclusive.

Key Exclusion Criteria:

• Clinical symptoms or signs of cardiomyopathy or heart failure.
• Exposure to any approved or investigational dystrophin restoration gene therapy product.
• Exposure to any approved or investigational dystrophin restoration product other than gene therapy (Except for exon-skipping therapy for Cohort A2).
• Exposure to any approved or investigational histone deacetylase inhibitor, antimyostatin therapy, therapy targeting transforming growth factor-beta ligands, or cell-based therapy.
• Use of any other pharmacological treatment, except for CS
• Treatment with immunosuppressant therapy (other than CS)
• History of fracture of the upper limb

Nonambulatory Participants Only (Cohort N1):

• Elbow-flexion contractures > 30° in both upper extremities.
• Forced vital capacity (FVC) of < 50% or requirement for daytime or nocturnal ventilation, except for nocturnal non-invasive ventilation AND inability to perform consistent FVC measurements within ± 15% during paired testing.