This study has been transitioned to CTIS with ID 2024-511492-15-00 check the CTIS register for the current data. Part 1:to evaluate the safety and tolerability of 2 doses (100 milligrams/kilogram [mg/kg] and 200 mg/kg) of eteplirsen in approximately…
ID
Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part 1: Incidence of Adverse Events (AEs)
Time Frame: Up to Week 148
Part 2: Change From Baseline in the NSAA Total Score at Week 144
Time Frame: Baseline, Week 144
Secondary outcome
Part 2: Change From Baseline in Time to Rise From the Floor, Time to Complete
10-Meter Walk/Run, and the Timed Stair Ascend Test Baseline.
Time Frame: Baseline, Week 144
Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk
Test (6MWT)
Time Frame: Baseline, Week 144
Part 2: Change from Baseline in Forced Vital Capacity Percent Predicted (FVC%p)
at Week 144
Time Frame: Baseline, Week 144
Part 2: Time to Loss of Ambulation (LOA)
Time Frame: Baseline up to Week 144
Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression
Time Frame: Baseline, Postdose (at Week 24, Week 48, or Week 144)
Part 2: Incidence of Adverse Events (AEs)
Time Frame: Baseline up to Week 148
Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen
Time Frame: 0 (predose) to 2 hours postdose up to Week 144
Background summary
This study will be comprised of 2 parts: Part 1 (dose escalation) will be
conducted to evaluate the safety and tolerability of 2 doses (100
milligrams/kilogram [mg/kg] and 200 mg/kg) of eteplirsen in approximately 10
participants with DMD; Part 2 (dose finding and dose comparison) will be
conducted for the evaluation of high doses (100 mg/kg and 200 mg/kg) and its
comparison with the 30 mg/kg dose of eteplirsen, in approximately 144
participants with genetically confirmed deletion mutations amenable to
treatment by skipping exon 51.
Study objective
This study has been transitioned to CTIS with ID 2024-511492-15-00 check the CTIS register for the current data.
Part 1:to evaluate the safety and tolerability of 2 doses (100
milligrams/kilogram [mg/kg] and 200 mg/kg) of eteplirsen in approximately 10
participants with DMD;
Part 2 (dose finding and dose comparison) will be conducted for the evaluation
of high doses (100 mg/kg and 200 mg/kg) and its comparison with the 30 mg/kg
dose of eteplirsen, in approximately 144 participants with genetically
confirmed deletion mutations amenable to treatment by skipping exon 51.
Study design
Design Details
Primary Purpose : Treatment
Allocation : Randomized
Interventional Model : Parallel Assignment
Masking : Quadruple (ParticipantCare ProviderInvestigatorOutcomes Assessor)
Masking Description: Part 1 is open-label, dose escalation; Part 2 is
double-blind, dose finding, and dose comparison Arms and Interventions
Participant Group/Arm:
- Experimental: Part 1: Eteplirsen
Participants will receive eteplirsen 100 mg/kg once weekly for at least 4
weeks, followed by eteplirsen 200 mg/kg once weekly for at least 4 weeks.
- Active Comparator: Part 2: Eteplirsen 30 mg/kg
Randomized participants will receive eteplirsen 30 mg/kg once weekly for up to
144 weeks.
- Experimental: Part 2: Eteplirsen 100 mg/kg
Randomized participants will receive eteplirsen 100 mg/kg once weekly before
the evaluation of the high doses occurs and then will receive the selected high
dose once weekly for up to 144 weeks.
- Experimental: Part 2: Eteplirsen 200 mg/kg
Randomized participants will receive eteplirsen 200 mg/kg once weekly before
the evaluation of the high doses occurs and then will receive the selected high
dose once weekly for up to 144 weeks.
Intervention
Drug: Eteplirsen
• Solution for intravenous (IV) infusion.
• Other Names:
• AVI-4658
• EXONDYS 51
• EXONDYS
Study burden and risks
Please refer for the procedures to the protocol tables 2-8 Schedule of events
(pages 8-23) or question E4.
The Possible side effects that are already known are described in the IB,
patient information letter and question E9.
First Street 215
Cambridge, MA 02142
US
First Street 215
Cambridge, MA 02142
US
Listed location countries
Age
Inclusion criteria
Inclusion Criteria:
• 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.
• Ambulatory participant, able to perform TTRISE in 10 seconds or less at the
time of screening visit.
• Able to walk independently without assistive devices.
• Have intact right and left biceps muscles or an alternative upper arm muscle
group.
• Have 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 throughout the
study.
• For ages 7 years and older, has stable pulmonary function (forced vital
capacity >=50 percent (%) of predicted and no requirement for nocturnal
ventilation). For ages 4 to 6 years, does not require support from ventilator
or non-invasive ventilation at time of screening.
Exclusion criteria
Exclusion Criteria:
• Use of any pharmacologic treatment (other than corticosteroids) within 12
weeks prior to randomization.
• 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 in the last 12 weeks
prior to first dose; Drisapersen in the last 36 weeks prior to first dose;
Suvodirsen in the last 12 weeks prior to first dose; Vamorolone in the last 12
weeks prior to first dose; and Eteplirsen (previous or current use).
• Major surgery within 3 months prior to randomization.
• Presence of any other significant neuromuscular or genetic disease other than
DMD.
• Presence of any known impairment of renal function and/or other clinically
significant illness.
• Has evidence of cardiomyopathy, as defined by left ventricular ejection
fraction less than <50% on the screening echocardiogram or Fridericia's
correction formula (QTcF) >=450 millisecond based on the screening
electrocardiograms (ECGs).
Other inclusion/exclusion criteria apply.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-511492-15-00 |
| EudraCT | EUCTR2018-001762-42-NL |
| ClinicalTrials.gov | NCT03992430 |
| CCMO | NL70639.000.20 |