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

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2015-002069-52-FR
• Date of registration: 12/01/2017
• Prospective Registration: Yes
• Primary sponsor: Sarepta Therapeutics, Inc.
• Public title: A research study of a new investigational medicinal product for the treatment of Duchenne Muscular Dystrophy patients
• Scientific title: A Double-Blind, Placebo-Controlled, Multicenter Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy - N/A
• Target sample size: 99
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002069-52
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, France, Germany, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trial Operations
• Affiliation: Voisin Consulting

• Name: Clinical Trial Operations
• Affiliation: Voisin Consulting

Key inclusion & exclusion criteria

Inclusion criteria:
1. Is a male with an established clinical diagnosis of DMD and an out-of-frame deletion amenable to:
? Exon 45 skipping (including but not limited to deletions of exons such as 12-44, 18-44, 44, 46-47, 46-48, 46-49, 46-51, 46-53, or 46-55) OR
? Exon 53 skipping (including but not limited to deletions of exons such as 42-52, 45-52, 47-52, 48-52,49-52, 50-52, 52, or 54-58) as documented by a genetic report from an accredited laboratory confirming deletion endpoints by multiplex ligation-dependent probe amplification or sequencing.
2. Is 7 to 13 years of age, inclusive.
3. Has stable pulmonary function (forced vital capacity % of predicted [FVC%] =50% and no requirement for nocturnal ventilation) that, in the Investigator’s opinion, is unlikely to decompensate over the duration of the study.
4. Has intact right and left biceps muscles (the preferred biopsy site) or 2 alternative upper arm muscle groups.
5. Has been on a stable dose or dose equivalent of oral corticosteroids for at least 24 weeks prior to Week 1 and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the study. Note: patients are allowed to take other medications (excluding other ribonucleic
acid [RNA] antisense or gene therapy agents) including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blocking agents (ARBs), ß adrenergic blockers, potassium, and coenzyme Q,
provided they have been on a stable dose for 12 weeks prior to Week 1 and the dose is expected to remain constant throughout the study.
6. Achieved a mean 6MWT distance of =300 to =450 meters (without assistance) at both the Screening and Baseline visits (prior to Week 1). The mean 6MWT distance at the Screening and Baseline visits is the average of 2 separate assessments on 2 consecutive days at each visit. The Baseline mean (average of Baseline Days 1 and 2) must be within 15% of the Screening mean distance (average of Screening Days 1 and 2).
7. Sexually active subjects must agree to use contraceptives for the entire duration of the study and for 90 days following the last dose. Both a male condom and a medically acceptable form of female
contraceptive (e.g., oral contraceptives) must be used.
8. Has (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with all the study requirements.
9. Is willing to provide 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: 99
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:
1. Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to Week 1 that may have an effect on muscle strength or function. Growth hormone for short stature and testosterone for delayed puberty are permitted if an endocrinologist has documented the diagnosis and medical necessity of treatment, and the patient has been on a stable dose for at least 24 weeks prior to Week 1.
2. Previous treatment with SMT C1100 (BMN-195) at any time.
3. Previous treatment with PRO045 or PRO053 within 24 weeks prior to Week 1.
4. Current or previous treatment with any other experimental treatment (other than deflazacort) within 12 weeks prior to Week 1.
5. Major surgery within 3 months prior to Week 1 or planned surgery for any time during this study, except for protocol-specified surgery, as applicable.
6. Presence of any other significant genetic disease other than DMD (e.g., dwarfism).
7. Presence of other clinically significant illness including significant cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or malignancy.
8. Use of any aminoglycoside antibiotic or statin within 12 weeks prior to Week 1 or anticipated need for an aminoglycoside antibiotic or statin during the study.
9. LVEF <50% on the Screening echocardiogram (ECHO) or QTcF =450 msec based on the Screening and Baseline ECG.
10. Loss of =30 degrees of plantar flexion from the normal range of movement at the ankle joint due to contracture (i.e., fixed loss of more than 10 degrees of plantar flexion from plantigrade, assuming normal range of dorsiflexion of 20 degrees).
11. 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. Additionally, patients who seem unable / unwilling to comply with the study procedures, in the Investigator’s opinion, are to be excluded.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Patients with Duchenne Muscular Dystrophy Amenable to Exon 45 or 53 Skipping
MedDRA version: 19.1 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: SRP-4045
Product Code: SRP-4045
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not yet available
CAS Number: 1422958-19-7
Current Sponsor code: SRP-4045
Other descriptive name: Phosphorodiamidate morpholino oligomer for exon 45 skipping
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: SRP-4053
Product Code: SRP-4053
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not yet available
CAS Number: 1422959-91-8
Current Sponsor code: SRP-4053
Other descriptive name: Phosphorodiamidate morpholino oligomer for exon 53 skipping
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Screening, Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96

Main Objective: The primary objective of this study is to evaluate the effect of SRP-4045 and SRP-4053 (combined-active group) compared to placebo on ambulation, endurance, and muscle function at Week 96, as measured by the 6-minute walk test (6MWT)

Primary end point(s): Change from Baseline at Week 96 on the 6MWT for the combined-active group compared to placebo

Secondary Objective: The secondary objectives are to evaluate the effect of SRP-4045 and SRP-4053 (combined-active group) on:
- Dystrophin protein expression in biopsied muscle tissue as measured by:
Western blot (quantification)
Immunohistochemistry (IHC) fiber intensity
- Functional status as measured by:
Ability to rise independently from the floor (without external support)
Loss of ambulation (LOA)
North Star Ambulatory Assessment (NSAA)
Respiratory muscle function, as measured by forced vital capacity (FVC) % predicted
Frequency of falls
Cardiac function, as measured by left ventricular ejection fraction (LVEF)
- Safety and tolerability of SRP-4045 and SRP-4053

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: ? Quantity of dystrophin protein expression: Baseline, week 48
? Intensity of dystrophin expression: Baseline, week 48
? Ability to rise independently from the floor: Screening, Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96
? LOA status: Week 96

Secondary end point(s): ?Change from Baseline at Week 48 in the quantity of dystrophin protein expression as measured by Western blot of biopsied muscle tissue
?Change from Baseline at Week 48 in the intensity of dystrophin expression in biopsied muscle tissue, as measured by IHC
? Ability to rise independently from the floor (without external support) at Week 96, as indicated by an NSAA subscore of "2" (without modification) or "1" (Gower's maneuver)
? LOA status at Week 96, defined as an inability to perform the 6MWT, or result of "0" meters on 6MWT
? Change from Baseline at Week 96
- NSAA total score
- FVC% predicted
- Frequency of falls
- LVEF

Secondary ID(s)

2015-002069-52-GB

4045-301

NCT02500381

Source(s) of Monetary Support

Sarepta Therapeutics, Inc.