Limb-Girdle Muscular Dystrophy, Type 2DPhase 1/2NCT01976091
A Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D)
A Phase 1/2 study testing SRP-9004 in people with Limb-Girdle Muscular Dystrophy, Type 2D, run by Sarepta Therapeutics, Inc..
Trial summary
This is an open-label, dose escalation gene transfer therapy study evaluating the safety of SRP-9004 (patidistrogene bexoparvovec) via isolated limb infusion (ILI) administration in approximately 6 participants with LGMD2D. Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Limb-Girdle Muscular Dystrophy, Type 2D
- What is being tested?
- SRP-9004
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2015to 14 Mar 2019
- Phase
- Phase 1/2
- 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 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Cohort 1A must be adult and wheelchair-dependent; Cohorts 1B and 2 will be participants of age 7 or older.
- Confirmed alpha-sarcoglycan deficiency or identified sarcoglycan alpha (SGCA) deoxyribonucleic acid (DNA) mutation.
- Participants enrolled in Cohorts 1B or 2 must be able to walk independently, but must exhibit signs of lower extremity weakness (that is, a Gowers' sign, use a handrail for climbing stairs) and walk ≤80% of predicted distance on the 6 minute walk test (6MWT) based on normative data.
Who cannot join
- Active viral infection based on clinical observations.
- The presence of SGCA mutations without weakness or loss of function.
- Symptoms or signs of cardiomyopathy.
- Serological evidence of human immunodeficiency virus (HIV), Hepatitis B, or C infection.
- Diagnosis of (or ongoing treatment for) an autoimmune disease.
- Participants with AAVrh74 or AAV8 binding antibody titers ≥ 1:50 as determined by enzyme-linked immunosorbent assay (ELISA) immunoassay.
- Other inclusion/exclusion criteria apply.
About this study
Official title: Phase I/IIA Gene Transfer Clinical Trial for LGMD2D (Alpha-Sarcoglycan Deficiency) Using scAAVrh74.tMCK.hSGCA
This is an open-label, dose escalation gene transfer therapy study evaluating the safety of SRP-9004 (patidistrogene bexoparvovec) via isolated limb infusion (ILI) administration in approximately 6 participants with LGMD2D.
- Conditions
- Limb-Girdle Muscular Dystrophy, Type 2D
- Being tested
- SRP-9004
- Keywords
- limb girdle muscular dystrophy, LGMD2D, alpha-sarcoglycan, gene transfer, adeno-associated virus
- Medical subject headings
- Sarcoglycanopathies, Muscular Dystrophies, Limb-Girdle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SRP-9004Genetic
Also called patidistrogene bexoparvovec
Isolated Limb Infusion (ILI)
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A: SRP-9004 Low Dose (Single Limb Perfusion) | Experimental | Non-ambulant participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to a single limb on Day 0. Receives: Genetic: SRP-9004 |
| Cohort 1B Low Dose (Bilateral Limb Perfusion) | Experimental | Participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to both limbs on Day 0. Receives: Genetic: SRP-9004 |
| Cohort 2 High Dose (Bilateral Limb Perfusion) | Experimental | Participants with LGMD2D will receive 1 high dose of SRP-9004 via ILI to both limbs on Day 0. Receives: Genetic: SRP-9004 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs).
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug related. An AE was considered serious if, in the view of the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Treatment-related Treatment Emergent Adverse Event (TEAE) is defined as an TEAE that was classified by the investigator as related to treatment.
Measured: Up to 2 Years
Secondary outcomes (1)
Change From Baseline of the Distance Walked in 6 Minutes (6MWT)
The 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course in 6 minutes (timed), and the distance walked (in meters) was recorded.
Measured: Baseline, Up to 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2013 (estimated)
- Study start1 Feb 2015
- Primary completion14 Mar 2019
- Study completion14 Mar 2019
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 (3)Papers the sponsor has linked to this study.
- Other trials for Limb-Girdle Muscular Dystrophy, Type 2DStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sarepta Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Nationwide Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Sarepta Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01976091
- Sponsor's protocol ID
- 9004-101
- Other IDs
- 5U01AR060911
- Status last verified
- Apr 2023
- First submitted
- 24 Jul 2013
- Last updated
- 15 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Mendell JR, Chicoine LG, Al-Zaidy SA, Sahenk Z, Lehman K, Lowes L, Miller N, Alfano L, Galliers B, Lewis S, Murrey D, Peterson E, Griffin DA, Church K, Cheatham S, Cheatham J, Hogan MJ, Rodino-Klapac LR. Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D by Isolated Limb Infusion. Hum Gene Ther. 2019 Jul;30(7):794-801. doi: 10.1089/hum.2019.006. Epub 2019 Apr 19.
PubMed 30838895Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR. Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol. 2010 Nov;68(5):629-38. doi: 10.1002/ana.22251.
PubMed 21031578Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR. Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol. 2009 Sep;66(3):290-7. doi: 10.1002/ana.21732.
PubMed 19798725
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIA Gene Transfer Clinical Trial for LGMD2D (Alpha-Sarcoglycan Deficiency) Using scAAVrh74.tMCK.hSGCA
- ClinicalTrials.gov ID
- NCT01976091
- Acronym / sponsor ID
- 9004-101
- Conditions
- Limb-Girdle Muscular Dystrophy, Type 2D
- Keywords
- limb girdle muscular dystrophy, LGMD2D, alpha-sarcoglycan, gene transfer, adeno-associated virus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Sarepta Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Nationwide Children's Hospital
- Study start
- 1 Feb 2015 (actual)
- Primary completion
- 14 Mar 2019 (actual)
- Study completion
- 14 Mar 2019 (actual)
- First posted
- 5 Nov 2013 (estimated)
- Results
- Posted 1 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, dose escalation gene transfer therapy study evaluating the safety of SRP-9004 (patidistrogene bexoparvovec) via isolated limb infusion (ILI) administration in approximately 6 participants with LGMD2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A: SRP-9004 Low Dose (Single Limb Perfusion) | Experimental | Genetic: SRP-9004Non-ambulant participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to a single limb on Day 0. |
| Cohort 1B Low Dose (Bilateral Limb Perfusion) | Experimental | Genetic: SRP-9004Participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to both limbs on Day 0. |
| Cohort 2 High Dose (Bilateral Limb Perfusion) | Experimental | Genetic: SRP-9004Participants with LGMD2D will receive 1 high dose of SRP-9004 via ILI to both limbs on Day 0. |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Cohort 1A must be adult and wheelchair-dependent; Cohorts 1B and 2 will be participants of age 7 or older.
- Confirmed alpha-sarcoglycan deficiency or identified sarcoglycan alpha (SGCA) deoxyribonucleic acid (DNA) mutation.
- Participants enrolled in Cohorts 1B or 2 must be able to walk independently, but must exhibit signs of lower extremity weakness (that is, a Gowers' sign, use a handrail for climbing stairs) and walk ≤80% of predicted distance on the 6 minute walk test (6MWT) based on normative data.
Key exclusion criteria (7 listed)
- Active viral infection based on clinical observations.
- The presence of SGCA mutations without weakness or loss of function.
- Symptoms or signs of cardiomyopathy.
- Serological evidence of human immunodeficiency virus (HIV), Hepatitis B, or C infection.
- Diagnosis of (or ongoing treatment for) an autoimmune disease.
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 |
|---|---|---|
| SRP-9004Also: patidistrogene bexoparvovecIsolated Limb Infusion (ILI) | Genetic | Cohort 1A: SRP-9004 Low Dose (Single Limb Perfusion), Cohort 1B Low Dose (Bilateral Limb Perfusion), Cohort 2 High Dose (Bilateral Limb Perfusion) |
Primary outcome
Number of Participants With Adverse Events (AEs).
Time frame: Up to 2 Years
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug related. An AE was considered serious if, in the view of the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Treatment-related Treatment Emergent Adverse Event (TEAE) is defined as an TEAE that was classified by the investigator as related to treatment.
1 secondary outcome
Change From Baseline of the Distance Walked in 6 Minutes (6MWT)
Time frame: Baseline, Up to 2 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30838895Mendell JR, Chicoine LG, Al-Zaidy SA, Sahenk Z, Lehman K, Lowes L, Miller N, Alfano L, Galliers B, Lewis S, Murrey D, Peterson E, Griffin DA, Church K, Cheatham S, Cheatham J, Hogan MJ, Rodino-Klapac LR. Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D by Isolated Limb Infusion. Hum Gene Ther. 2019 Jul;30(7):794-801. doi: 10.1089/hum.2019.006. Epub 2019 Apr 19.
- Background: PubMed 21031578Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR. Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol. 2010 Nov;68(5):629-38. doi: 10.1002/ana.22251.
- Background: PubMed 19798725Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR. Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol. 2009 Sep;66(3):290-7. doi: 10.1002/ana.21732.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SRP-9004 in people with Limb-Girdle Muscular Dystrophy, Type 2D, run by Sarepta Therapeutics, Inc..
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 7 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 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 1 Apr 2022). 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 Adverse Events (AEs). (time frame: Up to 2 Years). 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 NCT01976091, which also lists 3 linked publications.
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 15 Jun 2023.