AOC 1020 for Facioscapulohumeral Muscular Dystrophy

(FORTITUDE Trial)

Recruiting at 20 trial locations

Overseen By Avidity Biosciences, Inc.

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Avidity Biosciences, Inc.

Must not be taking: Investigative medications

Disqualifiers: Pregnancy, BMI >35, Bleeding disorders, others

Compensation: Varies

Number of Visits: Unknown

Duration: 9-10 months

90 Participants Needed

Trial Summary

What is the purpose of this trial?

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)

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken any investigative medication within 1 month before the screening.

What makes the drug AOC 1020 unique for treating facioscapulohumeral muscular dystrophy?

Currently, there is no established consensus on medication treatments for facioscapulohumeral muscular dystrophy, making AOC 1020 a potentially novel option. Other treatments like albuterol and vitamins have shown some benefits, but more clinical trials are needed to determine the effectiveness of new drugs like AOC 1020. ^{1 2 3 4 5}

Eligibility Criteria

Adults with confirmed FSHD1 or FSHD2 who can walk at least 10 meters and have at least one muscle region suitable for biopsy. They should not be pregnant, breastfeeding, or planning pregnancy soon, must follow contraceptive guidelines, and have a BMI under 35.0 kg/m^2. Those with recent biopsies, bleeding disorders, severe muscle wasting, or conditions that could affect study participation are excluded.

Inclusion Criteria

I have muscle weakness in both my arms and legs.

My FSHD (type 1 or 2) is confirmed by genetic testing.

I can walk 10 meters on my own or with a cane, stick, or braces.

Exclusion Criteria

Pregnancy, intent to become pregnant within 9 months after last planned dose of Study Drug, or active breastfeeding

Blood or plasma donation within 16 weeks of Study Day 1

Unwilling or unable to continue to comply with contraceptive requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AOC 1020 or placebo intravenously. Cohorts A & B receive five doses over 9 months, and Cohort C receives eight doses over approximately 10 months.

9-10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment. Cohorts A & B have a 12-week follow-up, and Cohort C has a 7-week follow-up.

7-12 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term after completing the main trial.

Treatment Details

Interventions

• AOC 1020
• Placebo

Trial Overview The trial is testing AOC 1020 against a placebo in adults with Facioscapulohumeral Muscular Dystrophy (FSHD). It's randomized and double-blind meaning neither the participants nor the researchers know who gets the real treatment versus placebo. The study will assess safety, tolerability of doses given intravenously and any potential benefits on muscle function.

Participant Groups

Group I: AOC 1020 Regimen 3 Experimental Treatment 1 Intervention

Cohort C: AOC 1020 Dose Regimen 3; Eight doses administered intravenously over approximately 10 months

Group II: AOC 1020 Regimen 2 Experimental Treatment 1 Intervention

Cohort B1: AOC 1020 Dose Regimen 2; Five doses administered intravenously over 9 months

Group III: AOC 1020 Regimen 1 Experimental Treatment 1 Intervention

Cohort A: AOC 1020 Dose Regimen 1; Five doses administered intravenously over 9 months

Group IV: Placebo (Saline) Regimen 1 Placebo Group 1 Intervention

Cohort A \& B: Placebo; Five doses administered intravenously over 9 months

Group V: Placebo (Saline) Regimen 2 Placebo Group 1 Intervention

Cohort C: Placebo; Eight doses administered intravenously over approximately 10 months

AOC 1020 is already approved in United States for the following indications:

Approved in United States as AOC 1020 for:

• Facioscapulohumeral muscular dystrophy (FSHD)

Who Is Running the Clinical Trial?

Avidity Biosciences, Inc.

Lead Sponsor

Trials

8

Recruited

960+

Findings from Research

The FSHD-COM, a new functional outcome measure for facioscapulohumeral muscular dystrophy (FSHD), showed excellent test-retest reliability with an intraclass correlation coefficient of 0.96, indicating it is a consistent tool for assessing patient function.

This composite measure demonstrated strong correlations with established disease metrics, suggesting it effectively reflects the severity and impact of FSHD, making it suitable for use in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facioscapulohumeral muscular dystrophy functional composite outcome measure. Eichinger, K., Heatwole, C., Iyadurai, S., et al.[2020]

Albuterol showed statistically significant improvements in elbow flexor muscle strength in three out of four clinical trials involving patients with facioscapulohumeral muscular dystrophy (FSHD).

Vitamins C and E, zinc gluconate, and selenomethionine also demonstrated significant benefits in muscle strength and endurance, while diltiazem and MYO-029 did not show any improvements, indicating varying efficacy among treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD): A Systematic Review. Aguirre, AS., Astudillo Moncayo, OM., Mosquera, J., et al.[2023]

In a study of 96 patients with facioscapulohumeral muscular dystrophy (FSHD), six early-onset cases were identified, indicating that early-onset FSHD can occur both in familial and sporadic forms.

The early-onset cases exhibited significant variability in symptoms, including progression of muscle weakness and associations with hearing loss and retinopathy, suggesting that early-onset FSHD is part of a broader clinical spectrum rather than a distinct form of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facioscapulohumeral muscular dystrophy in early childhood. Brouwer, OF., Padberg, GW., Wijmenga, C., et al.[2019]

The study involved 55 affected individuals and 48 at-risk individuals from a large family with facioscapulohumeral muscular dystrophy (FSHMD), showing that their clinical symptoms are similar to those seen in chromosome 4-linked FSHMD.

Genetic analyses revealed no linkage to known genetic markers for FSHMD on chromosome 4, suggesting that this family has a different genetic cause for their condition, supporting the idea of genetic heterogeneity in FSHMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Studies in Non-chromosome 4-Linked Facioscapulohumeral Muscular Dystrophy. Tim, RW., Gilbert, JR., Stajich, JM., et al.[2019]

Early onset facioscapulohumeral dystrophy (FSHD) affects about 10% of patients and is characterized by a more severe muscle phenotype and a higher prevalence of systemic features, such as hearing loss and retinal abnormalities, compared to adult-onset FSHD.

A study of 227 early onset FSHD patients revealed that 40% were wheelchair-dependent by an average age of 18.8 years, highlighting the need for more longitudinal studies to better understand the disease's progression and improve treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early onset facioscapulohumeral dystrophy - a systematic review using individual patient data. Goselink, RJM., Voermans, NC., Okkersen, K., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Facioscapulohumeral muscular dystrophy functional composite outcome measure. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD): A Systematic Review. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Facioscapulohumeral muscular dystrophy in early childhood. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical Studies in Non-chromosome 4-Linked Facioscapulohumeral Muscular Dystrophy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Early onset facioscapulohumeral dystrophy - a systematic review using individual patient data. [2018]