Duchenne Muscular Dystrophy MedDRA version: 20.1 Level: PT Classification code 10052655 Term: Duchenne muscular dystrophy gene carrier System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: SRP-5051
Product Code: SRP-5051
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: SRP-5051
CAS Number: 2101569-97-3
Current Sponsor code: SRP-5051
Other de
Sponsors
Sarepta Therapeutics, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: A patient must meet all of the following criteria to be eligible to participate in this study: 1. Is male. 2. Has a genetic diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51-skipping treatment. 3. Is 7 to 21 years of age, inclusive. 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. 5. 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 during this timeframe. 6. 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: 24 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 4 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A patient who meets any of the following criteria will be excluded from this study: 1. Has a LVEF < 40.0% based on an ECHO performed within 12 weeks prior to Screening or at the Screening visit. 2. Has a QT interval corrected with Fridericia’s formula = 450 msec on the Screening ECG. 3. Initiation or change of dosing (except for modifications to accommodate changes in weight) within 12 weeks prior to Screening for any of the following: angiotensin-converting enzyme inhibitors, angiotensin receptor-blocking agents, ß-blockers, or potassium. 4. Requires anti-arrhythmic and/or diuretic therapy for heart failure. 5. Has a FVC < 40.0% of predicted value (according to the American Thoracic Society/European Respiratory Society criteria) within 12 weeks prior to Screening or at Screening. 6. Has a current infection, or history of an infection within 12 weeks prior to Screening requiring treatment with an antibiotic. 7. Has a known kidney disease or had an acute kidney injury within 24 weeks prior to Screening. 8. Use of any herbal medication/supplement containing aristolochic acid. 9. Treatment with any exon 51-skipping therapy within 24 weeks prior to Screening, or with any experimental gene therapy for the treatment of DMD at any time. 10. Participation in an interventional clinical trial within 12 weeks prior to Screening. 11. Use of any aminoglycoside antibiotic or statin within 12 weeks prior to Screening. 12. Initiation or change of dosing within 12 weeks prior to Screening for over-the-counter preparations, such as herbal/nonherbal supplements, vitamins, minerals, and homeopathic preparations. 13. Major surgery within 12 weeks prior to Screening, or planned surgery or procedures that would interfere with the conduct of the study. 14. Presence of other clinically significant illness, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy. 15. Any other condition that, in the Investigator’s opinion, could interfere with the patient’s participation in the trial. 16. Inability to comply with the study protocol. 17. 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. 18. Any patient who is taking medications that increase the risk of bleeding, in the Investigator's opinion (eg, anticoagulants, antiplatelet agents, novel oral anticoagulants, selective norepinephrine reuptake inhibitors, etc.) 19. Platelet count < 150 × 103/µL.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: Multiple-Ascending-Dose (MAD) for Dose Determination To evaluate the safety and tolerability of multiple ascending doses of SRP-5051 (4.0, 10.0, 16.0, and 20.0 mg/kg), administered intravenously (IV) every 4 weeks, and determine the maximum tolerated dose (MTD) Part B – Dose Expansion • To evaluate exon-skipping and dystrophin protein production levels (derived from muscle) after additional treatment with SRP-5051, administered IV every 4 weeks at the MTD determined in Part A, in patients who have completed Part A;Secondary Objective: Part A – Multiple-Ascending-Dose (MAD) for Dose Determination To determine the pharmacokinetics (PK) of each dose level of the aforementioned multiple ascending doses of SRP-5051, administered IV every 4 weeks Part B – Dose Expansion • To evaluate the ongoing safety and tolerability of additional treatment with SRP-5051, administered IV every 4 weeks at the MTD determined in Part A, in patients who have completed Part A • To evaluate the clinical effect of additional treatment with SRP-5051, administered IV every 4 weeks at the MTD determined in Part A, in patients who have completed Part A • To determine the PK of SRP-5051, administered IV every 4 weeks at the MTD determined in Part A, in patients who have completed Part A;Primary end point(s): Part A – Multiple-Ascending-Dose (MAD) for Dose Determination • Incidence of AEs • Clinically significant laboratory abnormalities (eg, hematology, chemistry, coagulation, urinalysis) Part B – Dose Expansion • Change from Baseline biopsy in exon-skipping levels (as measured by PCR) in muscle. • Change from Baseline biopsy in dystrophin protein production levels (as measured by Western blot and/or other relevant methods) in muscle.;Timepoint(s) of evaluation of this end point: Part A – Multiple-Ascending-Dose (MAD) for Dose Determination All AEs will be reported from the time of providing signed informed consent/assent through the last follow-up visit. Clinically sign | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A – Multiple-Ascending-Dose (MAD) for Dose Determination • PK parameters Part B – Dose Expansion • Incidence of AEs • Clinically significant laboratory abnormalities (eg, hematology, chemistry, coagulation, urinalysis) • Change from Baseline assessment in the following, conducted at Part B, Week 24: o Forced vital capacity (FVC) (% predicted) calculation o North Star Ambulatory Assessment (NSAA) (in ambulatory patients) o Performance Upper Limb (PUL) o Brooke Upper Extremity Scale score (“Brooke Score”) • PK parameters at the MTD determined in Part A;Timepoint(s) of evaluation of this end point: Part A – Multiple-Ascending-Dose (MAD) for Dose Determination • PK parameters at each dose level Part B – Dose Expansion •All AEs will be reported from Baseline through the last follow-up visit. •Clinically significant laboratory abnormalities will be conducted in part B Week 24 • Change from baseline assessment in functional test conducted at part B, capture all timepoints • PK parameters at MTD | — |
Countries
Belgium, Canada, Germany, Ireland, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public Contactproject management
Syneos Health
Outcome results
None listed