AOC 1020 for Facioscapulohumeral Muscular Dystrophy

(FORTITUDE Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AOC 1020 for facioscapulohumeral muscular dystrophy (FSHD), a condition that weakens muscles in the face, shoulders, and upper arms. The researchers aim to determine if AOC 1020 is safe and effective when administered through an IV. Participants may receive either the actual treatment or a placebo (a substance with no active drug) for comparison. Individuals with confirmed FSHD who can walk at least 10 meters, with or without assistance, might qualify for this trial. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AOC 1020 has been tested for safety in people with facioscapulohumeral muscular dystrophy (FSHD). In one study, participants received AOC 1020 through an IV, and researchers closely monitored any side effects.

The safety results from these studies indicated that AOC 1020 was generally well-tolerated. Most side effects were mild to moderate, such as headaches or slight discomfort at the IV site. No major negative effects were directly linked to the treatment, suggesting it is relatively safe for people at this stage.

Since AOC 1020 is in an early phase of testing, its safety continues to be closely monitored. However, the results so far are promising, showing that the treatment does not pose significant safety risks, though more research is needed to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about AOC 1020 for Facioscapulohumeral Muscular Dystrophy (FSHD) because it introduces a new experimental approach to treating this genetic muscle disorder. Unlike traditional treatments that primarily address symptoms, AOC 1020 targets the root cause of FSHD by interfering with the expression of the DUX4 gene, which is linked to muscle degeneration in this condition. This targeted mechanism of action offers the potential for more effective management of the disease by directly addressing its underlying genetic causes. Additionally, AOC 1020 is administered intravenously, which could allow for precise dosing and potentially fewer side effects compared to existing treatments.

What evidence suggests that AOC 1020 might be an effective treatment for Facioscapulohumeral Muscular Dystrophy?

Research shows that AOC 1020, one of the treatments in this trial, may help treat facioscapulohumeral muscular dystrophy (FSHD). Studies found that patients receiving AOC 1020 had better muscle function than those on a placebo, another treatment arm in this trial. The treatment also reduced certain genes linked to FSHD by more than 50%, suggesting it might target the disease's root cause. Early results indicate improvements in patients' abilities. These findings offer hope that AOC 1020 could effectively treat FSHD. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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

Unwilling or unable to continue to comply with contraceptive requirements

Blood or plasma donation within 16 weeks of Study Day 1

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

Timeline for a Trial Participant

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.

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07038200

A Study to Evaluate Del-brax (Also Referred to as AOC ... ... Efficacy and Safety of Intravenous AOC 1020 for the Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD). Detailed Description. The study consists of a ...

2. aviditybiosciences.com aviditybiosciences.com/sites/default/files/2025-04/Final-NMSG-2024-FORTITUDE-Poster-16SEP24.pdf

Final-NMSG-2024-FORTITUDE-Poster-16SEP24.pdf FORTITUDE (AOC 1020-CS1) is a randomized, placebo-controlled, double-blind, global trial designed to evaluate the safety and tolerability of del-brax in adult ...

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06547216

NCT06547216 | Phase 2 Open-label Extension Study of ... This study will continue to evaluate the safety, tolerability, and efficacy of AOC 1020 in participants who were treated in the randomized, placebo-controlled, ...

4. neurologylive.com neurologylive.com/view/fda-accelerated-approval-open-fshd-agent-del-brax-newly-initiated-phase-3-study-confirm-efficacy

FDA Accelerated Approval Open for FSHD Agent Del-Brax ... Notably, treated patients demonstrated improved muscle function compared with both placebo and data from the ReSolve natural history study.

5. aviditybiosciences.com aviditybiosciences.com/pipeline/fshd

pipeline fshd Del-brax data demonstrated unprecedented and consistent reductions of greater than 50% in DUX4 regulated genes, trends of functional improvement, and favorable ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT07038200/a-study-to-evaluate-del-brax-also-referred-to-as-aoc-1020-in-participants-with-fshd?page=44&state=IA&city=Iowa%20city

A Study to Evaluate Del-brax (Also Referred to as AOC ... A Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous AOC 1020 for the Treatment ...