A research study to compare different doses of a new investigational medicinal product for treatment of certain patients with Duchenne muscular dystrophy

Phase 1

• Conditions: Duchenne Muscular Dystrophy; MedDRA version: 20.0Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2018-001762-42-NL
• Lead Sponsor: Sarepta Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-21
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 154

Inclusion Criteria

A patient must meet all of the following criteria to be eligible to participate in this study.
1. Be a male with an established clinical diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping (for example, deletions of exons 45-50, 47-50, 48-50, 49-50, 50, 52, and 52-63).
2. Be aged 4 to 13 years, inclusive
3. Ambulatory patient, able to perform TTRISE in 10 seconds or less at the time of screening visit.
4. Able to walk independently without assistive devices.
5. Has intact right and left biceps muscles (the preferred biopsy site) or an alternative upper arm muscle group that will allow for sufficiently sized (1 cm3) muscle biopsies to be obtained prior to and on treatment (for patients in the double-blind part of the study).
6. Has been on a stable dose or dose equivalent of oral corticosteroids for at least 12 weeks prior to randomization, and the dose is expected to remain constant (except for modifications to accommodate changes in weight and stress-related needs as per the recently published guidelines [Birnkrant 2018, Kinnett 2017]) throughout the study).
7. For ages 7 years and older, has stable pulmonary function (forced vital capacity =50% of predicted and no requirement for nocturnal ventilation) that, in the Investigator’s opinion, is unlikely to decompensate significantly over the duration of the study.
For ages 4 to 6 years , does not require support from ventilator or non-invasive ventilation at time of screening.
8. If sexually active, agree to use a male condom during such activity for the entire duration of the study and for 90 days after the last dose. The sexual partner must also use a medically acceptable form of contraceptive (ie, female oral contraceptives) during this timeframe. Acceptable methods of contraception include combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intra-uterine hormone-releasing system; bilateral tubal occlusion; vasectomized partner; sexual abstinence (True abstinence: When this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence [such as calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.); or condom in combination with either cap, diaphragm, or sponge with spermicide (double-barrier contraception).
9. Has (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with all the study requirements.
10. Is willing to provide informed assent (if applicable) and has (a) parent(s) or legal guardian(s) who is (are) willing to provide informed consent for the patient to participate in the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 154
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A patient who meets any of the following criteria will be excluded from this study:
1. Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to randomization that may have an effect on muscle strength or function. Growth hormone for short stature and testosterone for delayed puberty are permitted if physician has documented the diagnosis and medical necessity of treatment and if the patient has been on a stable dose for at least 24 weeks prior to randomization.
2. Current or previous treatment with any other experimental pharmacologic treatment for DMD or any prior exposure to antisense oligonucleotide, gene therapy or gene editing; except the following:
Ezutromid administered at least 12 weeks prior to first dose.
Drisapersen administered at least 36 weeks prior to first dose
Suvodirsen administered at least 12 weeks prior to first dose.
Vamorolone administered at least 12 weeks prior to first dose.
Eteplirsen (previous or current use)
Tamoxifen administered at least 4 weeks prior to first dose.
3. Major surgery within 3 months prior to randomization or planned surgery for any time during this study, except for allowed protocol-specified surgery, as applicable.
4. Presence of any significant neuromuscular or genetic disease other than DMD (eg, dwarfism).
5. Gamma-glutamyl transpeptidase (GGT) > 3 × the upper limit of normal (ULN) or serum bilirubin > ULN unexplained by Gilbert’s Syndrome.
6. Any known impairment of renal function (eg, estimated glomerular filtration rate [eGFR] = 60 mL/min as assessed by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] cystatin C based equation [Inker, 2012, Filler 2012]), or dipstick protein result +2, or persistent and unexplained dipstick protein result +1
7. Platelet count < the lower limit of normal.
8. Presence of other clinically significant illness including significant cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease or malignancy.
9. Has evidence of cardiomyopathy, as defined by left ventricular ejection fraction <50% on the screening ECHO or the Fridericia’s correction formula (QTcF) =450 milliseconds based on the screening ECGs.
10. 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.
11. Known hypersensitivity to eteplirsen or any excipients of eteplirsen.
12. Is, in the Investigator’s opinion, unable or unwilling to comply with the study procedures.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified