Clinical trial NCT05747924: Phase 1/2 Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Facioscapulohumeral Muscular Dystrophy 1
Facioscapulohumeral Muscular Dystrophy 2
Facio-Scapulo-Humeral Dystrophy
Atrophy, Facioscapulohumeral
Atrophies, Facioscapulohumeral
Facioscapulohumeral Atrophy
Muscular Dystrophies
Muscular Dystrophy, Facioscapulohumeral
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
FSH
Keywords: FORTITUDE
Avidity
Avidity Biosciences
AOC 1020
Lead sponsor: Avidity Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-28
Enrollment: 90
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (Cohorts A & B)
timeFrame: Through study completion, up to Day 365
measure: Change in DUX4-regulated gene expression in muscle biopsies (Cohort C)
timeFrame: Day 120
measure: Change in a circulating biomarker of FSHD disease biology (Cohort C)
timeFrame: Day 120
Secondary outcomes:
measure: Plasma pharmacokinetic (PK) parameters of AOC 1020 (Cohorts A & B)
timeFrame: Through study completion; up to Day 365
measure: Plasma pharmacokinetic (PK) parameters of AOC 1020 (Cohorts A & B)
timeFrame: Through study completion; up to Day 365
measure: Plasma pharmacokinetic (PK) parameters of AOC 1020 (Cohorts A & B)
timeFrame: Through study completion; up to Day 365
measure: Muscle drug concentration (Cohorts A, B & C)
timeFrame: Day 120
measure: Change in DUX4-regulated gene expression in muscle biopsies (Cohort C)
timeFrame: Day 120
measure: % Change in circulating creatine kinase (Cohort C)
timeFrame: Through study completion; up to Day 365
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
city: London
country: United Kingdom
facility: University College London
city: Sheffield
country: United Kingdom
facility: University of Sheffield
Study officials:
References: