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

Phase 1

Recruiting

• Conditions: FSHD; FSHD1; FSHD2; FMD; FMD2; Fascioscapulohumeral Muscular Dystrophy; Fascioscapulohumeral Muscular Dystrophy Type 1; Fascioscapulohumeral Muscular Dystrophy Type 2; Dystrophies, Facioscapulohumeral Muscular; Dystrophy, Facioscapulohumeral Muscular
• Interventions: Drug: AOC 1020; Drug: Placebo

• Registration Number: NCT05747924
• Lead Sponsor: Avidity Biosciences, Inc.

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 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 enroll in the open-label extension, they will be followed for 12-weeks after their last dose of study medication.

Study Timeline

• Study First Submitted: 2023-02-17
• Study First Submitted QC: 2023-02-27
• Study First Posted: 2023-02-28
• Study Start: 2023-04-04
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-22
• Last Update Posted: 2024-10-24
• Primary Completion: 2026-10
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AOC 1020 Regimen 1	AOC 1020	Cohort A: AOC 1020 Dose Regimen 1; Five doses administered intravenously over 9 months
AOC 1020 Regimen 2	AOC 1020	Cohort B1: AOC 1020 Dose Regimen 2; Five doses administered intravenously over 9 months
AOC 1020 Regimen 3	AOC 1020	Cohort C: AOC 1020 Dose Regimen 3; Eight doses administered intravenously over approximately 10 months
Placebo (Saline) Regimen 1	Placebo	Cohort A \& B: Placebo; Five doses administered intravenously over 9 months
Placebo (Saline) Regimen 2	Placebo	Cohort C: Placebo; Eight doses administered intravenously over approximately 10 months

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (Cohorts A & B)	Through study completion, up to Day 365
Change in DUX4-regulated gene expression in muscle biopsies (Cohort C)	Day 120
Change in a circulating biomarker of FSHD disease biology (Cohort C)	Day 120

Secondary Outcome Measures

Name	Time	Method
Plasma pharmacokinetic (PK) parameters of AOC 1020 (Cohorts A & B)	Through study completion; up to Day 365	Observed area under the curve
Muscle drug concentration (Cohorts A, B & C)	Day 120	Concentration of siRNA component in skeletal muscle
Change in DUX4-regulated gene expression in muscle biopsies (Cohort C)	Day 120
% Change in circulating creatine kinase (Cohort C)	Through study completion; up to Day 365

Trial Locations

Locations (17)

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of California San Diego; 🇺🇸 San Diego, California, United States

University of Colorado; 🇺🇸 Denver, Colorado, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Rare Disease Research; 🇺🇸 Atlanta, Georgia, United States

Kansas University Medical Center; 🇺🇸 Kansas City, Kansas, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

University of Ottawa; 🇨🇦 Ottawa, Ontario, Canada

University College London; 🇬🇧 London, United Kingdom

University of Sheffield; 🇬🇧 Sheffield, United Kingdom