Atrophies, Facioscapulohumeral, Atrophy, Facioscapulohumeral, Dystrophies, Facioscapulohumeral Muscular, Dystrophies, Landouzy-Dejerine, Dystrophy, Facioscapulohumeral Muscular, Dystrophy, Landouzy-Dejerine, Facioscapulohumeral Atrophy, Facio-Scapulo-Humeral Dystrophy, Facioscapulohumeral Muscular Dystrophy 1, Facioscapulohumeral Muscular Dystrophy 2, Fascioscapulohumeral Muscular Dystrophy, Fascioscapulohumeral Muscular Dystrophy Type 1, Fascioscapulohumeral Muscular Dystrophy Type 2, FMD, FMD2, FSH, FSHD, FSHD1, FSHD2, FSH Muscular Dystrophy, Landouzy Dejerine Dystrophy, Landouzy-Dejerine Muscular Dystrophy, Landouzy-Dejerine Syndrome, Muscular Dystrophies, Muscular Dystrophy, Facioscapulohumeral, Muscular Dystrophy, Landouzy Dejerine, Progressive Muscular Dystrophy
Conditions
Keywords
FORTITUDE, Avidity, Avidity Biosciences, AOC 1020
Brief summary
A Randomized, Double-blind, Placebo-controlled, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of AOC 1020 Administered Intravenously to Participants with Facioscapulohumeral Muscular Dystrophy (FSHD)
Detailed description
AOC 1020-CS1 is a first-in-human, 3-part, multi-center, Phase 1/2, randomized, double-blind, placebo-controlled study designed to evaluate safety, tolerability, pharmacokinetics and to explore pharmacodynamics and efficacy of single and multiple-doses of AOC 1020 administered intravenously in participants with FSHD Type 1 (FSHD1) and FSHD Type 2 (FSHD2). Cohort A comprises a placebo-controlled dose titration cohort (Cohort A1) which includes a nested single and multiple dose schedule. Cohort B comprises a placebo-controlled, nested single ascending dose (SAD)/multiple ascending dose (MAD) cohort (Cohort B1). Cohort C comprises a randomized, placebo-controlled, expansion cohort (Cohort C1). For each of Cohorts A, B, and C the study duration is 12 months as the active treatment period is approximately 9 months for Cohorts A & B and approximately 10.5 months for Cohort C followed by a 12-week follow-up period for Cohorts A & B and a 7-week follow-up period for Cohort C. Once participants have completed active treatment with follow-up through 12 months, they may have the option to participate in a planned open-label extension. If patients do not immediately roll over into the open-label extension study or decline participation, they will be followed for 18 weeks after their last dose of study medication.
Interventions
AOC 1020 will be administered via intravenous (IV) infusion
Placebo will be administered via intravenous (IV) infusion
Sponsors
Study design
Eligibility
Inclusion criteria
* FSHD1 or FSHD2 diagnosis confirmed by documented genetic testing (testing provided by Sponsor) * Ambulatory and able to walk 10 meters (with or without assistive devices such as one cane, walking stick or braces) * At least 1 muscle region suitable for biopsy (testing provided by Sponsor) * Muscle weakness in both upper and lower body, as determined by Investigator
Exclusion criteria
* Pregnant or intends to become pregnant while on study, or active breastfeeding * Unwilling or unable to continue to comply with contraceptive requirements * Body mass index (BMI) \>35.0 kg/m2 at Screening * History of muscle biopsy within 30 days of the screening biopsy or planning to undergo any nonstudy muscle biopsies over the duration of the study * History of bleeding disorders, significant keloid, or other skin or muscle conditions (e.g., severe muscle wasting) that, in the opinion of the Investigator, makes the participant unsuitable for serial muscle biopsy * Anticipated survival less than 2 years * Blood or plasma donation within 16 weeks of Study Day 1 * Any contraindication to MRI * Any abnormal lab values, conditions or diseases that, in the opinion of the investigator or Sponsor, would make the participant unsuitable for the study or could interfere with participation or completion of the study * Treatment with any investigative medication within 1 month (or 5 half-lives of the drug, whichever is longer) of Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (Cohorts A & B) | Through study completion, up to Day 365 | — |
| Change in plasma KHDC1L (Part C) | Across months 3 to 12 | Ratio to Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma pharmacokinetic (PK) parameters of AOC 1020 (Cohorts A & B) | Through study completion; up to Day 365 | Observed maximum concentration |
| Muscle drug concentration (Cohorts A & B) | Day 120 | Concentration of siRNA component in skeletal muscle |
| Change in circulating creatine kinase (Cohort C) | Across months 3 to 12 | Ratio to Baseline |
Countries
Canada, United Kingdom, United States