An Open-Label Study of Golodirsen in Non-Ambulant Patients With Duchenne Muscular Dystrophy

NCT04708314 | Terminated Phase 4 FDA Drug

• 1 other identifier: 19-06-001
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label study to evaluate the safety and tolerability of golodirsen injection in Non-ambulant DMD patients with confirmed genetic mutations amenable to treatment by exon 53 skipping (Golodirsen). Golodirsen 30 mg/kg will be administered as an intravenous (IV) infusion over approximately 35 to 60 minutes once a week during the treatment period (up to 96 weeks). After the treatment period, patients can go into a safety extension period (not to exceed 48 weeks) until the patient is able to transition to commercially available drug or a separate golodirsen study. Safety will be regularly assessed throughout the study via the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations. Exploratory assessments, including pulmonary function tests (PFTs), upper extremity testing, and other measurements of functional status, will occur at functional assessment visits every 12 weeks over the first year of treatment and approximately every 24 weeks over the second year of treatment.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• Explore the safety and tolerability of Golodirsen in number of participants with Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment emergent adverse events were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug \[up to 148 weeks\]) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

  Baseline up to 96 weeks

Other Outcomes (4)

• Change from Baseline to Week 96 in Forced Vital Capacity Percent (FVC%) Predicted

  Baseline up to 96 weeks

• Change from Baseline to Week 96 in Performance of Upper Limb (PUL) Score

  Baseline up to 96 weeks

• Change from Baseline to Week 96 in Brooke scale for upper extremity

  Baseline up to 96 weeks

Study Arms (1)

30 mg/kg

OTHER

Golodirsen 30 mg/kg will be administered as an intravenous (IV) infusion over approximately 35 to 60 minutes once a week during the treatment period (up to 96 weeks). After the treatment period, patients can go into a safety extension period (not to exceed 48 weeks) until the patient is able to transition to commercially available drug or a separate golodirsen study.

Drug: Golodirsen 50 MG/1 ML Intravenous Solution [VYONDYS 53]

Interventions

Golodirsen 50 MG/1 ML Intravenous Solution [VYONDYS 53] DRUG

Vyondys 53

30 mg/kg

Eligibility Criteria

• Age: 7 Years+
• Gender Eligibility Details: Only male patients are affected by this condition
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Be a male with DMD with a mutation that may be amenable to exon 53 skipping as documented by a genetic report from an accredited laboratory confirming mutation endpoints by multiplex ligation-dependent probe amplification.
• Be 7 years of age or older.
• Has been on a stable dose of oral corticosteroids for at least 24 weeks prior to study drug administration and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the study or has not received corticosteroids for at least 24 weeks prior to study drug administration and does not expect to start corticosteroids throughout the study.
• Be unable to ambulate ("non-ambulatory"). By definition, loss of ambulation means patient or caregiver reported continuous wheelchair use that has been verified by a clinical evaluator. The following conditions should be met:
• Condition is not secondary to acute worsening of mobility due to orthopedic morbidity (eg, fracture, sprain, or injury) or surgical procedure.
• Unable to perform 10-meter walk run test.
• Has stable pulmonary function that, in the opinion of the Investigator, is unlikely to decompensate over the study period.
• Patients who are post-pubertal and sexually active must agree to use, for the entire duration of the study and for 90 days post last dose, a male condom and the female sexual partner must also use a medically acceptable form of birth control (eg, oral contraceptives).
• Able to understand and comply with all study requirements, in the Investigator's opinion, or if under the age of 18 years, must have a parent(s) or legal guardian(s) who is able to understand.
• Willing to provide informed consent to participate in the study, or if under the age of 18 years, be willing to provide informed assent, if applicable, and have a parent(s) or legal guardian(s) who is willing to provide informed consent for the patient to participate in the study.

You may not qualify if:

• Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks of study drug administration that in the opinion of the Investigator might have an effect on skeletal muscle strength or function (eg, growth hormone, anabolic steroids).
• Previous treatment with any investigational drug or exon skipping therapy within the last 3 months.
• Major change in physiotherapy regimen within the past 3 months or expected change over the study period.
• Major surgery within 3 months of study drug administration or planned major surgery for any time during this study.
• Presence of other clinically significant illness that cannot be attributed to classic Duchenne disease course including significant cardiac, pulmonary, hepatic, renal, hematologic, immunologic, behavioral disease, or malignancy.
• Systemic use of any aminoglycoside antibiotic within 12 weeks of study drug administration or anticipated need for use of an aminoglycoside antibiotic or statin during the study.
• Must not require antiarrhythmic and/or antidiuretic therapy for heart failure. Patients are allowed to take other medication including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blocking agents, β blockers or potassium, provided they have been on a stable dose for 24 weeks prior to study drug administration and the dose is expected to remain constant throughout the study.
• Prior or ongoing medical condition that could, in the Investigator's opinion, adversely affect the safety of the patient, make it unlikely that the course of treatment would be completed, or impair the assessment of study results.

Sponsors & Collaborators

• Rare Disease Research, LLC: lead
• Sarepta Therapeutics, Inc.: collaborator

Study Sites (2)

Rare Disease Research, LLC

Atlanta, Georgia, 30318, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

golodirsen

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: January 13, 2021
• Study Start: October 31, 2020
• Primary Completion: May 13, 2021
• Study Completion: May 13, 2021
• Last Updated: May 17, 2021

Record last verified: 2021-05

Locations

US (2)