A research study of a new investigational medicinal product for the treatment of Duchenne Muscular Dystrophy patients

Phase 1

Conditions: Duchenne Muscular Dystrophy
MedDRA version: 20.1Level: PTClassification code 10052655Term: Duchenne muscular dystrophy gene carrierSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2019-000601-77-NL

Lead Sponsor: Sarepta Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Male

Target Recruitment: 57

Inclusion Criteria

Inclusion Criteria for Patients Previously Treated with SRP-5051
Patients previously treated with SRP-5051 must meet all of the following criteria to participate in this study:
I 1. Has received prior SRP-5051 treatment in Part A of this study or in Study 5051-102.
I 2. If sexually active, agrees to use a male condom during such activity for the entire duration of the study and for 90 days after the last dose of study drug. The sexual partner must also use a highly effective form of contraceptive (refer to Appendix 1 for guidance on highly effective contraceptive methods) during this timeframe.
I 3. Is willing to provide informed consent or informed assent (if applicable) and has (a) parent(s) or legal guardian(s) who is (are) willing to provide written informed consent for the patient to participate in the study.

Inclusion Criteria for Patients Treatment-Naïve to SRP-5051
Patients who are treatment-naïve to SRP-5051 must meet all of the following criteria to participate in this study:
I 1. Is male.
I 2. Is 7 to 21 years of age, inclusive.
I 3. Has a genetic diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51-skipping treatment.
I 4. Has been on a stable dose of oral corticosteroids for at least 12 weeks prior to study drug administration or has not received corticosteroids for at least 12 weeks prior to study drug administration.
I 5. Has stable pulmonary function (FVC = 40% of predicted and no requirement for nocturnal ventilation as a result of the complications of DMD) that, in the Investigator’s opinion, is unlikely to decompensate significantly over the duration of the study. NOTE: patients on nocturnal ventilation because of sleep apnea, obesity, or other conditions caused by corticosteroid use are allowed to participate in the study if FVC % predicted is = 40
I 6. If sexually active, agrees to use a male condom during such activity for the entire duration of the study and for 90 days after the last dose of study drug. The sexual partner must also use a highly effective form of contraceptive (refer to Appendix 1 for guidance on highly effective contraceptive methods) during this timeframe.
I 7. Is willing to provide informed consent or informed assent (if applicable) and has (a) parent(s) or legal guardian(s) who is (are) willing to provide written informed consent for the patient to participate in the study.).
Are the trial subjects under 18? yes
Number of subjects for this age range: 57
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria for Patients Previously Treated with SRP-5051:
E 1. Has a current infection, or history of an infection within 12 weeks prior to Day -1 requiring intravenous treatment with an antibiotic, or oral antibiotics that may affect renal or cardiac function.
E 2. Has a known kidney disease (identified by eGFR [calculated using Schwartz 2012 cystatin C equation] of < 90 mL/min/1.73 m2) or had an acute kidney injury within 24 weeks prior to Screening.
E 3. Major surgery within 12 weeks prior to Screening, or planned surgery or procedures that would interfere with the conduct of the study.
E 4. Presence of other clinically significant illness, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy.
E 5. Any other condition that, in the Investigator’s opinion, could interfere with the patient’s participation in the trial, including body weight loss to < 18 kg.
E 6. Inability to comply with the study protocol.
E 7. Is an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members of the employees or the Investigator.
E 8. Any patient who is taking medications that increase the risk of bleeding, in the Investigator’s opinion
E 9. Platelet count < 150 × 10^3/µL.
E 10. Known hypersensitivity to the study drug (ie, SRP-5051) or to any of its components.
E 11. Has:
a. Hypomagnesemia (< lower limit of normal) at Screening
b. Other abnormal electrolyte values considered clinically significant by the Investigator upon medical review and in consultation with the Medical Monitor at Screening;
c. Serum creatinine > upper limit of normal (ULN) at Screening.
E 12. Has quantitative urinalysis or urine microscopy findings above the ULN for RBCs or WBCs.
E 13. Urine Protein/Creatinine Ratio = 200 mg/g and UACR = 30 mg/g OR 24-hour urine values for protein = 200 mg/24 hr at Screening and albumin = 30 mg/24 hr. (Note that 24-hour urine protein does not need to be performed during screening if the UPCR/UACR criteria are met).
E 14. GGT > 3 × ULN at Screening
E 15. Is being treated with a proton pump inhibitor, loop diuretic, or thiazide diuretic at the time of study initiation.
E 16. Treatment with any exon 51-skipping therapy within 4 weeks prior to Screening, or with any experimental gene therapy for the treatment of DMD at any time.
For other exclusion criteria please refer to Protocol

Exclusion Criteria for Patients Treatment-Naïve to SRP-5051:
E 1. History of hypomagnesemia within 12 weeks prior to Screening.
For TN Cohort patients entering the study in Part B
E 2. Has body weight < 18 kg.
E 3. Has a diagnosis of diabetes (any type).
E 4. Initiation or change of dosing (except for modifications to accommodate changes in weight or changes in standard of care) within 12 weeks prior to Screening for any of the following: angiotensin-converting enzyme inhibitors, angiotensin receptor-blocking agents, ß-blockers, or potassium.
E 5. Requires anti-arrhythmic and/or diuretic therapy for heart failure.
E 6. Has a current infection, or history of an infection within 12 weeks prior to Day -1 requiring intravenous treatment with an antibiotic, or oral antibiotics that may affect renal or cardiac function.
E 7. Has a known kidney disease (identified by eGFR [calculated using Schwartz cystatin C equation] of < 90 mL/min/1.73 m2) or had an acute kidney injury w

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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