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

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.


Eligibility Criteria:
Inclusion Criteria:

1. 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.
2. Be 7 years of age or older.
3. 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.
4. 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:

   1. Condition is not secondary to acute worsening of mobility due to orthopedic morbidity (eg, fracture, sprain, or injury) or surgical procedure.
   2. Unable to perform 10-meter walk run test.
5. Has stable pulmonary function that, in the opinion of the Investigator, is unlikely to decompensate over the study period.
6. 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).
7. 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.
8. 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.

Exclusion Criteria:

1. 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).
2. Previous treatment with any investigational drug or exon skipping therapy within the last 3 months.
3. Major change in physiotherapy regimen within the past 3 months or expected change over the study period.
4. Major surgery within 3 months of study drug administration or planned major surgery for any time during this study.
5. 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.
6. 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.
7. 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.
8. If the patient is asymptomatic but has a LVEF \< 40% at Screening or clinically significant at the discretion of Investigator, the Investigator should discuss inclusion of patient in the study with the appropriate institutional safety committee or medical monitor.
9. 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.