Facioscapulohumeral Dystrophy, Facio-Scapulo-Humeral Dystrophy, Facioscapulohumeral Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy 1, Facioscapulohumeral Muscular Dystrophy 2, Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1), Fascioscapulohumeral Muscular Dystrophy, Fascioscapulohumeral Muscular Dystrophy Type 1, Fascioscapulohumeral Muscular Dystrophy Type 2, FSHD, FSHD1, FSHD2, FSHD - Facioscapulohumeral Muscular Dystrophy, FSH Muscular Dystrophy, Landouzy Dejerine Dystrophy, Landouzy-Dejerine Muscular Dystrophy, Landouzy-Dejerine Syndrome
Conditions
Keywords
Avidity, Avidity Biosciences, del-brax, del brax, delbrax, AOC1020, AOC 1020, delpacibart braxlosiran, FORTITUDE-3, FORTITUDE Phase 3, FORTITUDE, FORTITUDE 3
Brief summary
A Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous AOC 1020 for the Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD)
Detailed description
The study duration is approximately 22 months, consisting of a screening period of up to 6 weeks, a 78-week active treatment period, and a 12-week follow-up period (18 weeks from the last dose). Participants will be randomized to receive an intravenous infusion of either delbrax or placebo at the clinical study site every 6 weeks for a total of 13 doses. The final dose will occur at Week 72, followed by a final assessment at Week 78. After completion of the Week 78 visit, eligible participants will have the option to enroll in an open-label extension (OLE) study, pending regulatory approval. Participants who decline participation in the OLE will be followed for 12 weeks for safety. An Independent Data Monitoring Committee (IDMC) comprising members independent and external to the Sponsor will review safety, tolerability, and efficacy (as needed) data of this study at regular intervals.
Interventions
DRUGAOC-1020
Del-brax will be administered by intravenous (IV) infusion.
DRUGPlacebo
Placebo will be administered by intravenous (IV) infusion.
Sponsors
Avidity Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Clinical and genetic diagnosis of FSHD1 or FSHD2 * Ability to walk independently at pre-specified walking speed (orthoses and ankle braces allowed) for at least 10 meters at screening * Adequate muscle strength based on QMT composite score
Exclusion criteria
* Breastfeeding, pregnancy, or intent to become pregnant during the study * Unwilling or unable to comply with contraceptive requirements * Abnormal lab values, conditions or diseases that would make the participant unsuitable for the study * Blood Pressure \> 140/90 mmHg at Screening * Treatment with another investigational drug or biological agent within 1 month of Screening or 5 half-lives of the drug, whichever is longer * Treatment with an oligonucleotide within 9 months of Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to Week 78 in Quantitative Muscle Testing (QMT) total composite score (PPN) | Baseline through Week 78 | Assessment of muscle strength using standardized quantitative measurements |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to Week 78 in 10MWRT | Baseline through Week 78 | Assessment of the time required to walk or run 10 meters as quickly and safely as possible |
| Change from Baseline to Week 78 in Timed Up-and-Go (TUG) | Baseline through Week 78 | Assessment of functional mobility by measuring the time required to stand up from a chair, walk 3 meters, turn, return, and sit down |
| Change from Baseline to Week 78 in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Item Bank v2.0-Physical Function-Short Form 20a Questionnaire | Baseline through Week 78 | Assessment of patient-reported physical function using the PROMIS Physical Function Short Form 20a questionnaire |
| Change from Baseline to Week 78 in PROMIS Fatigue | Baseline through Week 78 | Assessment of patient-reported fatigue using the PROMIS Fatigue questionnaire |
| Change from Baseline to Week 78 in Worst Pain Numeric Rating Scale (NRS) | Baseline through Week 78 | Assessment of the severity and impact of fatigue over the previous 7 days using the self-reported PROMIS Fatigue Short Form 6a questionnaire |
| Change from Baseline to Week 78 in Patient Global Impression of Severity/Change (PGI-S/PGI-C) | Baseline through Week 78 | Assessment of participant-reported disease severity and change in disease status using the Patient Global Impression of Severity/Change (PGI-S/PGI-C) scales |
| Change from Baseline to Week 78 in Quality of Life in Neurological Disorders (NeuroQoL) Upper Extremity Function | Baseline through Week 78 | Assessment of health-related quality of life using the Quality of Life in Neurological Disorders (Neuro-QoL) questionnaire |
| Change from Baseline to Week 78 in NeuroQoL Sleep Disturbance | Baseline through Week 78 | Assessment of participant-reported sleep disturbance using the Neuro-QoL Sleep Disturbance questionnaire |
| Change from Baseline to Week 78 in DUX4-regulated plasma KHDC1L | Baseline through Week 78 | Assess of changes from baseline in circulating PD biomarkers relevant to FSHD |
| Change from Baseline to Week 78 in Serum CK | Baseline through Week 78 | Assess of changes from baseline in circulating PD biomarkers relevant to FSHD |
Countries
Canada, Denmark, France, Germany, Italy, Japan, Netherlands, Spain, United Kingdom, United States
Contacts
CONTACTAvidity Biosciences, Inc., A Novartis Company
Outcome results
None listed