Duchenne Muscular Dystrophy (DMD)Phase 2NCT02420379

Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy

A Phase 2 study testing eteplirsen in people with Duchenne Muscular Dystrophy (DMD), run by Sarepta Therapeutics, Inc. at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is an open-label study to assess the safety, tolerability, efficacy and pharmacokinetics of eteplirsen in patients with early stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping. Read more about this study

Who is it for?: Ages 4 to 6 years, men only
Conditions the study is for: Duchenne Muscular Dystrophy (DMD)
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: 33 participants
Where: 13 sitesUnited States
Study dates: 30 Jun 2015to 17 Dec 2018
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 4 to 6 years
Men only
No healthy volunteers
Child

Who may be able to join

Male 4-6 years of age.
Diagnosis of DMD, genotypically confirmed.
Stable dose of oral corticosteroids for at least 12 weeks or has not received corticosteroids for at least 12 weeks.
Intact right and left biceps muscles or two alternative upper arm muscle groups.
Parent that is willing to provide consent and comply with study procedures.

Who cannot join

Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks that may have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids).
Previous or current treatment with any other experimental treatments within 12 weeks or participation in any other clinical trial within 6 months.
Major surgery within 3 months prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study activities.
Presence of other clinically significant illness.

Trial locations and contacts

13 sites in 1 country.

City, postcode or hospital

13 sites in 1 country

United States13 sites

Rare Disease Research Center
Atlanta, Georgia, 30318
Children's Hospital of Atlanta
Atlanta, Georgia, 30324
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Florida, Shands Hospital
Gainesville, Florida, 32610
University of Iowa Children's Hospital
Iowa City, Iowa, 52242
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Neuromuscular Research Center of Arizona
Phoenix, Arizona, 85028
Shriners Hospital for Children
Portland, Oregon, 97239
University of California, Davis Medical Center
Sacramento, California, 95817
Seattle Children's Hospital
Seattle, Washington, 98105
St. Louis Children's Hospital
St Louis, Missouri, 63110
Stanford University Medical Center
Stanford, California, 94305

Other trials in United States

About this study

Official title: An Open-Label, Multi-Center Study to Evaluate the Safety, Efficacy and Tolerability of Eteplirsen in Early Stage Duchenne Muscular Dystrophy

Read the detailed description

Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients.

Clinical efficacy, including functional tests and MRI, will be assessed at regularly scheduled study visits. Patients will undergo one baseline and one follow-up muscle biopsy.

Population and serial PK will be collected.

Conditions: Duchenne Muscular Dystrophy (DMD)
Being tested: eteplirsen
Keywords: DMD, Duchenne muscular dystrophy, eteplirsen, 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®
Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks.

Study groups in NCT02420379
Study group	Role	What they receive
Open-Label	Experimental	Approximately 20 patients will receive weekly infusions of eteplirsen 30 mg/kg . Receives: Drug: eteplirsen
Control Group	No intervention	Approximately 20 patients with DMD not amenable to exon 51 skipping will be observed for 96 weeks.

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 TEAEs, and TEAEs Leading to Discontinuation
Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment emergent adverse events were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug [up to 100 weeks]) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Measured: Baseline up to 100 weeks
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs
Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Measured: Baseline up to 100 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Measured: Baseline up to 100 weeks
Number of Participants With at Least One Abnormal Physical Examination Finding
Physical examinations, full and brief, were performed by the Investigator, a physician Sub-Investigator, or a Nurse Practitioner (if licensed in the state or province to perform physical examinations). Full physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; skin; lymph nodes; and musculoskeletal and neurological systems. Number of participants with at least one abnormal physical examination findings were reported. Abnormality in physical examinations was based on Investigator's discretion.
Measured: Baseline up to 100 weeks
Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs
Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECGs were reported as TEAEs.
Measured: Baseline up to 96 weeks
Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECHO were reported as TEAEs.
Measured: Baseline up to 96 weeks

Secondary outcomes (2)

Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96
Change from baseline in dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Week 48 and 96 was reported. For each time point, 2 blocks of tissues were analyzed by Western blot, each with 2 replicates of gels to determine the dystrophin level as compared to a healthy individual (Percent Normal). The block average value from 2 replicate gels was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for all analyses. In case only 1 gel was available for a block, then that value was used as the block average value.
Measured: Baseline, Week 48 and 96
Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96
Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry at Week 48 and 96 was reported.
Measured: Baseline, Week 48 and 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jun 201517 Dec 2018

First posted17 Apr 2015 (estimated)
Study start30 Jun 2015
Primary completion17 Dec 2018
Study completion17 Dec 2018

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.
Other trials for Duchenne Muscular Dystrophy (DMD)Studies 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02420379
Sponsor's protocol ID: 4658-203
Status last verified: Dec 2020
First submitted: 10 Apr 2015
Last updated: 25 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 25 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Multi-Center Study to Evaluate the Safety, Efficacy and Tolerability of Eteplirsen in Early Stage Duchenne Muscular Dystrophy
ClinicalTrials.gov ID: NCT02420379
Acronym / sponsor ID: 4658-203
Conditions: Duchenne Muscular Dystrophy (DMD)
Keywords: DMD, Duchenne muscular dystrophy, eteplirsen, Dystrophin, exon 51
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: Sarepta Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 30 Jun 2015 (actual)
Primary completion: 17 Dec 2018 (actual)
Study completion: 17 Dec 2018 (actual)
First posted: 17 Apr 2015 (estimated)
Results: Posted 22 Jul 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients.

Clinical efficacy, including functional tests and MRI, will be assessed at regularly scheduled study visits. Patients will undergo one baseline and one follow-up muscle biopsy.

Population and serial PK will be collected.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Open-Label	Experimental	Drug: eteplirsenApproximately 20 patients will receive weekly infusions of eteplirsen 30 mg/kg .
Control Group	No intervention	–Approximately 20 patients with DMD not amenable to exon 51 skipping will be observed for 96 weeks.

Who may qualify

Ages: 4 to 6 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

Male 4-6 years of age.
Diagnosis of DMD, genotypically confirmed.
Stable dose of oral corticosteroids for at least 12 weeks or has not received corticosteroids for at least 12 weeks.
Intact right and left biceps muscles or two alternative upper arm muscle groups.
Parent that is willing to provide consent and comply with study procedures.

Key exclusion criteria (4 listed)

Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks that may have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids).
Previous or current treatment with any other experimental treatments within 12 weeks or participation in any other clinical trial within 6 months.
Major surgery within 3 months prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study activities.
Presence of other clinically significant illness.

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®Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks.	Drug	Open-Label

Primary outcome

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Time frame: Baseline up to 100 weeks
Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment emergent adverse events were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug [up to 100 weeks]) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs
Time frame: Baseline up to 100 weeks
Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs
Time frame: Baseline up to 100 weeks
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Number of Participants With at Least One Abnormal Physical Examination Finding
Time frame: Baseline up to 100 weeks
Physical examinations, full and brief, were performed by the Investigator, a physician Sub-Investigator, or a Nurse Practitioner (if licensed in the state or province to perform physical examinations). Full physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; skin; lymph nodes; and musculoskeletal and neurological systems. Number of participants with at least one abnormal physical examination findings were reported. Abnormality in physical examinations was based on Investigator's discretion.
Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs
Time frame: Baseline up to 96 weeks
Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECGs were reported as TEAEs.
Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs
Time frame: Baseline up to 96 weeks
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECHO were reported as TEAEs.

2 secondary outcomes

Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96
Time frame: Baseline, Week 48 and 96
Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96
Time frame: Baseline, Week 48 and 96

Results and safety

Results posted to the registry on 22 Jul 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Eteplirsen 30 mg/kg	26	25
Control Group (Untreated) (Non-exon 51 Amenable Participants)	7	3

Primary outcome: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation

Time frame: Baseline up to 100 weeks. Count of participants. Unit: Participants

Measure	Eteplirsen 30 mg/kg n = 26	Control Group (Untreated) (Non-exon 51 Amenable Participants) n = 7
Participants with TEAEs	26	5
Participants with Serious TEAEs	4	0
Participants with TEAEs leading to discontinuation	0	0

Population analysed: Full set included all participants who were enrolled in the eteplirsen group and received at least 1 dose of eteplirsen as well as all participants who were enrolled in the untreated group and had at least 1 assessment post-enrollment assessment.

Primary outcome: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs

Time frame: Baseline up to 100 weeks. Count of participants. Unit: Participants

Measure	Eteplirsen 30 mg/kg n = 26	Control Group (Untreated) (Non-exon 51 Amenable Participants) n = 7
SC: Blood creatine phosphokinase increased	1	0
Hematology: Anaemia	1	0
Hematology: Iron deficiency Anaemia	1	0
Urinalysis: chromaturia	3	0
Urinalysis: pollakiuria	1	0
Coagulation: Thrombocytopenia	0	0

Population analysed: Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment post-enrollment assessment.

Primary outcome: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs

Time frame: Baseline up to 100 weeks. Count of participants. Unit: Participants

Measure	Eteplirsen 30 mg/kg n = 26	Control Group (Untreated) (Non-exon 51 Amenable Participants) n = 7
Pyrexia	11	1
Pulse pressure increased	1	0
Tachycardia	1	0

Population analysed: Full set included all participants who were enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment post-enrollment assessment.

Primary outcome: Number of Participants With at Least One Abnormal Physical Examination Finding

Time frame: Baseline up to 100 weeks. Count of participants. Unit: Participants

Measure	Eteplirsen 30 mg/kg n = 26	Control Group (Untreated) (Non-exon 51 Amenable Participants) n = 7
Value	23	4

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to 100 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Eteplirsen 30 mg/kg	4 of 26 (15.4%)	26 of 26 (100%)	0 of 26
Control Group (Untreated) (Non-exon 51 Amenable Participants)	0 of 7 (0%)	5 of 7 (71.4%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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 director

Sarepta Therapeutics, Inc.

13 sites in 1 country: 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 (DMD), run by Sarepta Therapeutics, Inc. at 13 sites in United States.

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 5 inclusion and 4 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 25 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. 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 22 Jul 2020). 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 TEAEs, and TEAEs Leading to Discontinuation (time frame: Baseline up to 100 weeks). The study lists 6 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 NCT02420379.

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 25 Jan 2021.