Duchenne Muscular DystrophyPhase 2NCT03218995
Study of Eteplirsen in Young Participants With Duchenne Muscular Dystrophy (DMD) Amenable to Exon 51 Skipping
A Phase 2 study testing Eteplirsen in people with Duchenne Muscular Dystrophy, run by Sarepta Therapeutics, Inc. at 4 sites in 4 countries.
Trial summary
This is a multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, and PK of once-weekly IV infusions of eteplirsen in approximately 12 male participants, ages 6 months to 48 months (inclusive), who have genotypically confirmed DMD with a deletion mutation amenable to exon 51 skipping. Read more about this study
- Who is it for?
- Ages 6 to 48 months, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- Eteplirsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 16 Aug 2017to 10 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 48 months
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Male between 6 months to 48 months of age (inclusive)
- Diagnosis of DMD with a deletion mutation amenable to exon 51 skipping
- Parent(s) or legal guardian(s) who is willing to provide written informed consent
Who cannot join
- Received treatment that might have an effect on muscle strength or function within 12 weeks prior to dosing
- Received previous or current treatment with any experimental treatment
- Clinically significant illness other than DMD
- Clinically significant laboratory abnormality
- Any other condition that could interfere with the participation in the study.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
United Kingdom1 site
UCL Great Ormond Street Institute of Child Health
London, WC1N 1EH
About this study
Official title: An Open-Label Safety, Tolerability, and Pharmacokinetics Study of Eteplirsen in Young Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
This is a multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, and PK of once-weekly IV infusions of eteplirsen in approximately 12 male participants, ages 6 months to 48 months (inclusive), who have genotypically confirmed DMD with a deletion mutation amenable to exon 51 skipping.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- Eteplirsen
- Keywords
- DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EteplirsenDrug
Also called AVI-4658, EXONDYS 51®
Infusion for intravenous use.
| Study group | Role | What they receive |
|---|---|---|
| Eteplirsen | Experimental | Eteplirsen will be administered once every 7 days by intravenous (IV) infusion starting on Day 1 for up to 96 weeks. The starting dose will be 2 milligrams/kilogram (mg/kg) eteplirsen, with escalation to 4, 10, 20, and 30 mg/kg for 10 weeks, and then participants will continue to receive eteplirsen at 30 mg/kg for the duration of the study. Receives: Drug: Eteplirsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Abnormalities presented at Baseline were considered AEs if they reoccurred after resolution or worsen during the AE collection period. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Measured: Baseline up to Week 100
Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality
Clinical laboratory parameters that were evaluated included
- Any Grade ≥2 (moderate) or serious event without an alternative etiology that the Investigator deemed was related to study drug
- Two consecutive drug-related serum creatinine levels ≥2*upper limit of normal (ULN) without an alternative etiology
- Creatine kinase (CK) levels >50,000 units/liter (U/L)
- A confirmed, unexplained, increase in gamma glutamyl transferase (GGT) >3*ULN and either an increase in bilirubin >2*ULN or nascent prothrombin time >2*ULN concurrently, without an alternative etiology
Measured: Baseline up to Week 100
Number of Participants With at Least 1 Markedly Abnormal Vital Sign
The vital sign parameters that were evaluated included blood pressure, heart rate, respiration, and temperature. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Measured: Baseline up to Week 100
Abnormal Changes From Baseline or Worsening of Physical Examination Findings
Data not collected during the study for this Outcome Measure. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Measured: Baseline up to Week 100
Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO)
The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the centrally read ECG report were clinically significant. Clinical significance was defined as any variation in ECG findings that had medical relevance resulting in an alteration in medical care. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the ECHO report were clinically significant. Clinical significance was defined as any variation in ECHO findings that had medical relevance resulting in an alteration in medical care. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Measured: Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96
Secondary outcomes (4)
Maximum Plasma Concentration (Cmax) of Eteplirsen
Measured: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen
Measured: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma
Measured: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Amount of Drug Eliminated in Urine
Amount of unchanged drug excreted in urine from time 0 to 4 hours after completion of dosing is reported.
Measured: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2017
- Study start16 Aug 2017
- Primary completion10 Mar 2021
- Study completion10 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by Sarepta Therapeutics, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sarepta Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study chair, Sarepta Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03218995
- Sponsor's protocol ID
- 4658-102
- Status last verified
- Nov 2021
- First submitted
- 9 Jul 2017
- Last updated
- 9 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mercuri E, Seferian AM, Servais L, Deconinck N, Stevenson H, Ni X, Zhang W, East L, Yonren S, Muntoni F; 4658-102 Study Group. Safety, tolerability and pharmacokinetics of eteplirsen in young boys aged 6-48 months with Duchenne muscular dystrophy amenable to exon 51 skipping. Neuromuscul Disord. 2023 Jun;33(6):476-483. doi: 10.1016/j.nmd.2023.03.008. Epub 2023 Mar 24.
PubMed 37207382
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Safety, Tolerability, and Pharmacokinetics Study of Eteplirsen in Young Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
- ClinicalTrials.gov ID
- NCT03218995
- Acronym / sponsor ID
- 4658-102
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Sarepta Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 16 Aug 2017 (actual)
- Primary completion
- 10 Mar 2021 (actual)
- Study completion
- 10 Mar 2021 (actual)
- First posted
- 17 Jul 2017 (actual)
- Results
- Posted 9 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, and PK of once-weekly IV infusions of eteplirsen in approximately 12 male participants, ages 6 months to 48 months (inclusive), who have genotypically confirmed DMD with a deletion mutation amenable to exon 51 skipping.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eteplirsen | Experimental | Drug: EteplirsenEteplirsen will be administered once every 7 days by intravenous (IV) infusion starting on Day 1 for up to 96 weeks. The starting dose will be 2 milligrams/kilogram (mg/kg) eteplirsen, with escalation to 4, 10, 20, and 30 mg/kg for 10 weeks, and then participants will continue to receive eteplirsen at 30 mg/kg for the duration of the study. |
Who may qualify
- Ages
- 6 to 48 months
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Male between 6 months to 48 months of age (inclusive)
- Diagnosis of DMD with a deletion mutation amenable to exon 51 skipping
- Parent(s) or legal guardian(s) who is willing to provide written informed consent
Key exclusion criteria (5 listed)
- Received treatment that might have an effect on muscle strength or function within 12 weeks prior to dosing
- Received previous or current treatment with any experimental treatment
- Clinically significant illness other than DMD
- Clinically significant laboratory abnormality
- Any other condition that could interfere with the participation in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EteplirsenAlso: AVI-4658, EXONDYS 51®Infusion for intravenous use. | Drug | Eteplirsen |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug
Time frame: Baseline up to Week 100
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Abnormalities presented at Baseline were considered AEs if they reoccurred after resolution or worsen during the AE collection period. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality
Time frame: Baseline up to Week 100
Clinical laboratory parameters that were evaluated included * Any Grade ≥2 (moderate) or serious event without an alternative etiology that the Investigator deemed was related to study drug * Two consecutive drug-related serum creatinine levels ≥2*upper limit of normal (ULN) without an alternative etiology * Creatine kinase (CK) levels >50,000 units/liter (U/L) * A confirmed, unexplained, increase in gamma glutamyl transferase (GGT) >3*ULN and either an increase in bilirubin >2*ULN or nascent prothrombin time >2*ULN concurrently, without an alternative etiology
Number of Participants With at Least 1 Markedly Abnormal Vital Sign
Time frame: Baseline up to Week 100
The vital sign parameters that were evaluated included blood pressure, heart rate, respiration, and temperature. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Abnormal Changes From Baseline or Worsening of Physical Examination Findings
Time frame: Baseline up to Week 100
Data not collected during the study for this Outcome Measure. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO)
Time frame: Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96
The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the centrally read ECG report were clinically significant. Clinical significance was defined as any variation in ECG findings that had medical relevance resulting in an alteration in medical care. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the ECHO report were clinically significant. Clinical significance was defined as any variation in ECHO findings that had medical relevance resulting in an alteration in medical care. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
4 secondary outcomes
Maximum Plasma Concentration (Cmax) of Eteplirsen
Time frame: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen
Time frame: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma
Time frame: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Amount of Drug Eliminated in Urine
Time frame: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37207382Mercuri E, Seferian AM, Servais L, Deconinck N, Stevenson H, Ni X, Zhang W, East L, Yonren S, Muntoni F; 4658-102 Study Group. Safety, tolerability and pharmacokinetics of eteplirsen in young boys aged 6-48 months with Duchenne muscular dystrophy amenable to exon 51 skipping. Neuromuscul Disord. 2023 Jun;33(6):476-483. doi: 10.1016/j.nmd.2023.03.008. Epub 2023 Mar 24.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study chair
Sarepta Therapeutics, Inc.
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eteplirsen in people with Duchenne Muscular Dystrophy, run by Sarepta Therapeutics, Inc. at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium, France, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug (time frame: Baseline up to Week 100). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03218995, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2021.