Phase 1/2 Study of AOC 1020 in Adults With Facioscapulohumeral Muscular Dystrophy (FSHD)

Study Overview
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Brief Summary
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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 Adult Participants with Facioscapulohumeral Muscular Dystrophy (FSHD)

Detailed Description
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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 adult participants with FSHD Type 1 (FSHD1) and FSHD Type 2 (FSHD2). Part A is a dose titration design which includes a single and multiple dose schedule with 1 cohort. Part B is a single-ascending and multiple-ascending dose design with 2 cohorts. Part C is a parallel, multi-dose cohort design with 1 cohort. For each of Part A, B, and C the patient duration is 12 months as the active treatment period is approximately 9 months followed by a 3-month follow-up period. Once participants have completed active treatment and the follow-up period, they may have the option to participate in a planned open-label extension. If patients do not enroll in the open-label extension, they will be followed through a 6-month safety follow-up period.

Official Title
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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 Adult Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)

Conditions
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FSH, FMD2, Muscular Dystrophy, Facioscapulohumeral, FSHD, FSHD1, FSHD2, FMD, Fascioscapulohumeral Muscular Dystrophy, Fascioscapulohumeral Muscular Dystrophy Type 1, Fascioscapulohumeral Muscular Dystrophy Type 2, Dystrophies, Facioscapulohumeral Muscular, Dystrophy, Facioscapulohumeral Muscular, Facioscapulohumeral Muscular Dystrophy 1, Facioscapulohumeral Muscular Dystrophy 2, Facio-Scapulo-Humeral Dystrophy, Atrophy, Facioscapulohumeral, Atrophies, Facioscapulohumeral, Facioscapulohumeral Atrophy, Muscular Dystrophies, FSH Muscular Dystrophy, Landouzy Dejerine Dystrophy, Landouzy-Dejerine Muscular Dystrophy, Dystrophies, Landouzy-Dejerine, Dystrophy, Landouzy-Dejerine, Landouzy-Dejerine Syndrome, Muscular Dystrophy, Landouzy Dejerine, Progressive Muscular Dystrophy

Intervention / Treatment
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* Drug: AOC 1020
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Diagnosed with congenital or infantile FSHD Pregnancy, intent to become pregnant within 9 months after last planned dose of Study Drug, 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AOC 1020 Regimen 1<br>Part A: AOC 1020 Dose Regimen 1; Five doses administered intravenously over 9 months | Drug: AOC 1020<br>* AOC 1020 will be administered via intravenous (IV) infusion<br>|
| Experimental: AOC 1020 Regimen 2<br>Part B1 & C: AOC 1020 Dose Regimen 2; Five doses administered intravenously over 9 months | Drug: AOC 1020<br>* AOC 1020 will be administered via intravenous (IV) infusion<br>|
| Experimental: AOC 1020 Regimen 3<br>Part B2 & C: AOC 1020 Dose Regimen 3; Five doses administered intravenously over 9 months | Drug: AOC 1020<br>* AOC 1020 will be administered via intravenous (IV) infusion<br>|
| Placebo Comparator: Placebo (Saline)<br>Part A, B & C: Placebo; Five doses administered intravenously over 9 months | Drug: Placebo<br>* Placebo will be administered via intravenous (IV) infusion<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events |  | Through study completion, up to Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic (PK) parameters of AOC 1020 | Observed maximum concentration | Through study completion; up to Day 365 | 
| Plasma pharmacokinetic (PK) parameters of AOC 1020 | Observed half-life | Through study completion; up to Day 365 | 
| Plasma pharmacokinetic (PK) parameters of AOC 1020 | Observed area under the curve | Through study completion; up to Day 365 | 
| Muscle drug concentration | Concentration of siRNA component in skeletal muscle | Day 120 | 
| Urine drug concentration | Fraction of drug excreted in urine | 0 - 24 hours after first and third dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avidity, FORTITUDE, Avidity Biosciences, AOC 1020