Duchenne Muscular DystrophyPhase 1/2NCT02354781

Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy

A Phase 1/2 study testing rAAV1.CMV.huFollistin344 in people with Duchenne Muscular Dystrophy, run by Jerry R. Mendell at 1 site 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

Who is it for?: Ages 7 years and older, men only
Conditions the study is for: Duchenne Muscular Dystrophy
What is being tested?: rAAV1.CMV.huFollistin344
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 1 siteUnited States
Study dates: Jan 2015to Nov 2017
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
Men only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Age 7 or older
Confirmed DMD gene mutations
Impaired muscle function based on clinical evidence including difficulty climbing stairs, getting from the floor (Gowers' sign), and weakness of individual muscles of extremities
Males of any ethnic group will be eligible
Ability to cooperate with study procedures including muscle testing.
Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception
Subjects must be on stable dose of prednisone for three months at time of enrollment or be started on oral dose of daily prednisone regimen for 30 days prior to gene transfer. Study participants will continue prednisone post gene transfer unless there is adverse event that warrants prednisone taper or withdrawal.

Who cannot join

Active viral infection based on clinical observations.
The presence of a DMD gene mutation without weakness or loss of function
Symptoms or signs of cardiomyopathy, including:
Dyspnea on exertion, pedal edema, shortness of breath upon lying flat, or rales at the base of the lungs
Echocardiogram with ejection fraction below 40%
Serological evidence of HIV infection, or Hepatitis A, B or C infection

Show all 10Show fewer

Diagnosis of (or ongoing treatment for) an autoimmune disease
Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
Subjects with rAAV1 binding antibody titers > 1:50 as determined by ELISA immunoassay
Abnormal laboratory values for liver, kidney, CBC, in the clinically significant range, based upon normal values in the Nationwide Children's Hospital Laboratory

Trial locations and contacts

1 site in 1 country.

United States1 site

Nationwide Children's Hospital
Columbus, Ohio, 43205

Other trials in United States

About this study

Official title: Phase I/II Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy

The proposed clinical trial is an outgrowth of the safety record and functional improvement seen in the BMD follistatin gene therapy trial. In this study the investigators propose to inject AAV1.CMV.huFS344 at a total dose of 2.4E12 vg/kg to six DMD patients. This dose will be divided between gluteal muscles, quadriceps and tibialis anterior. This is a wider distribution of vector than given to BMD patients, who overall improved the distance walked on the 6MWT without adverse events related to viral transduction into a single muscle.

Read the detailed description

The primary objective of this study is safety and endpoints will include hematology, serum chemistry, urinalysis, immunologic response to rAAV1 and follistatin, and reported history and observations of symptoms. Efficacy measures will be used as secondary outcomes and include the distance walked on the 6MWT, functional tests by PT, life quality questionnaire, MRI, EIM, and muscle biopsy. Subject will have follow up visits on days 7, 14, 30, 45, 60, 90, 180 and 9,12, 18 and 24 months post-gene transfer.

Conditions: Duchenne Muscular Dystrophy
Being tested: rAAV1.CMV.huFollistin344
Keywords: DMD, muscular dystrophy, Follistatin
Medical subject headings: Muscular Dystrophy, Duchenne, Muscular Dystrophies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

rAAV1.CMV.huFollistin344Biological
Six DMD patients will receive rAAV1.CMV.huFollistatin344 to both limbs by multiple injections to gluteal muscles, quadriceps and tibialis anterior muscles.

Study groups in NCT02354781
Study group	Role	What they receive
Experimental	Experimental	The vector will be delivered to both limbs via multiple, direct intramuscular injections of rAAV1.CMV.huFollistin344; the number of injections per muscle will depend on the size of the patient. A total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) will be delivered to the lower limbs of 6 DMD subjects Receives: Biological: rAAV1.CMV.huFollistin344

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Dose Limiting Toxicity (DLT) Adverse Events as Assessed by 21 CFR 312.32.
Dose limiting toxicity (DLT) is defined as any adverse event that is possibly, probably, or definitely related to the study agent. This would include any grade 3 according to the classification given above. Study enrollment will be halted by the investigators when any subject experiences a Grade 3, or higher adverse event toxicity that is possibly, probably, or definitely related to the study drug. Only those adverse events requiring treatment will qualify as DLT.
The classification for adverse events to be used is the following:
1. Mild adverse event; did not require treatment
2. Moderate adverse event; resolved with treatment
3. Severe adverse event; inability to carry on normal activities; required professional medical attention
4. Life-threatening or permanently disabling adverse event
5. Fatal adverse event In this grading system, "severe" is not equivalent to seriousness.
Measured: DLT Adverse events will be recorded from the date of dosing and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of dosing and for up to 2 years after gene therapy administration.

Secondary outcomes (3)

Muscle Function Measured by Six-minute Walk Test (6MWT)
Number of subjects with increased distance walked in meters on the Six Minute Walk Test. The participant was asked to walk a set course of 25 meters for 6 minutes (timed) and the distance walked in meters was recorded. Increases from baseline in 6MWT distance are indicative of improvement and decreases from baseline indicate worsening.
Measured: 2 years
Expression of Viral DNA (qPCR), and Follistatin Transgene in Muscle Tissue
Muscle biopsies on quadriceps muscles a muscle biopsy on one leg at baseline screening visit and the post gene transfer biopsy on the opposite leg at day 180. Muscle tissue obtained at biopsy will also be assessed for viral DNA (qPCR), and follistatin transgene expression.
Measured in CMV.FS344 Gene Copy Number in Genomic DNA (Copies/ug DNA)
Measured: 180.days
Improvement of Muscle Function as Measured by North Star Ambulatory Assessment (NSAA)
Overall Improvement in North Star Ambulatory Assessment
The activities are graded as follows:
2 - "Normal" - no obvious modification of activity
1 - Modified method but achieves goal independent of physical assistance from another 0 - Unable to achieve independently This scale is ordinal with 34 as the maximum score indicating fully-independent function.
Measured: 2 years

Timeline

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

Jan 2015Nov 2017

First posted3 Feb 2015 (estimated)
Study startJan 2015
Primary completionNov 2017
Study completionNov 2017

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 (5)Papers the sponsor has linked to this study.
Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
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: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02354781
Sponsor's protocol ID: 14-00630
Status last verified: Sep 2023
First submitted: 26 Jan 2015
Last updated: 11 Oct 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM, Lowes LP, Alfano LN, Berry K, Meadows E, Lewis S, Braun L, Shontz K, Rouhana M, Clark KR, Rosales XQ, Al-Zaidy S, Govoni A, Rodino-Klapac LR, Hogan MJ, Kaspar BK. A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Mol Ther. 2015 Jan;23(1):192-201. doi: 10.1038/mt.2014.200. Epub 2014 Oct 17.
PubMed 25322757
Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall WR, Walker CM, Weisbrode SE, Janssen PM, Clark KR, Sahenk Z, Mendell JR, Kaspar BK. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med. 2009 Nov 11;1(6):6ra15. doi: 10.1126/scitranslmed.3000112.
PubMed 20368179
Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve. 2009 Mar;39(3):283-96. doi: 10.1002/mus.21244.
PubMed 19208403
Miller TM, Kim SH, Yamanaka K, Hester M, Umapathi P, Arnson H, Rizo L, Mendell JR, Gage FH, Cleveland DW, Kaspar BK. Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19546-51. doi: 10.1073/pnas.0609411103. Epub 2006 Dec 12.
PubMed 17164329
Bian X, Snow ZK, Zinn CJ, Gowan CC, Conley SM, Bratulin AL, Elhusseiny KM, Miller J, Tchkonia T, Kirkland JL, Lerman LO, Hickson LJ. Activin A Antagonism with Follistatin Reduces Kidney Fibrosis, Injury, and Cellular Senescence-Associated Inflammation in Murine Diabetic Kidney Disease. Kidney360. 2025 Mar 28;6(8):1278-1291. doi: 10.34067/KID.0000000776.
PubMed 40152935

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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All Duchenne Muscular Dystrophy trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy
ClinicalTrials.gov ID: NCT02354781
Acronym / sponsor ID: 14-00630
Conditions: Duchenne Muscular Dystrophy
Keywords: DMD, muscular dystrophy, Follistatin
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 3 participants (actual)
Lead sponsor: Jerry R. MendellUniversity, hospital or other
Collaborators: Duchenne Alliance, Milo Therapeutics
Study start: Jan 2015
Primary completion: Nov 2017 (actual)
Study completion: Nov 2017 (actual)
First posted: 3 Feb 2015 (estimated)
Results: Posted 15 Apr 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

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Experimental	Experimental	Biological: rAAV1.CMV.huFollistin344The vector will be delivered to both limbs via multiple, direct intramuscular injections of rAAV1.CMV.huFollistin344; the number of injections per muscle will depend on the size of the patient. A total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) will be delivered to the lower limbs of 6 DMD subjects

Who may qualify

Ages: 7 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (7 listed)

Age 7 or older
Confirmed DMD gene mutations
Impaired muscle function based on clinical evidence including difficulty climbing stairs, getting from the floor (Gowers' sign), and weakness of individual muscles of extremities
Males of any ethnic group will be eligible
Ability to cooperate with study procedures including muscle testing.

Key exclusion criteria (10 listed)

Active viral infection based on clinical observations.
The presence of a DMD gene mutation without weakness or loss of function
Symptoms or signs of cardiomyopathy, including:
Dyspnea on exertion, pedal edema, shortness of breath upon lying flat, or rales at the base of the lungs
Echocardiogram with ejection fraction below 40%

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
rAAV1.CMV.huFollistin344Six DMD patients will receive rAAV1.CMV.huFollistatin344 to both limbs by multiple injections to gluteal muscles, quadriceps and tibialis anterior muscles.	Biological	Experimental

Primary outcome

Number of Dose Limiting Toxicity (DLT) Adverse Events as Assessed by 21 CFR 312.32.
Time frame: DLT Adverse events will be recorded from the date of dosing and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of dosing and for up to 2 years after gene therapy administration.
Dose limiting toxicity (DLT) is defined as any adverse event that is possibly, probably, or definitely related to the study agent. This would include any grade 3 according to the classification given above. Study enrollment will be halted by the investigators when any subject experiences a Grade 3, or higher adverse event toxicity that is possibly, probably, or definitely related to the study drug. Only those adverse events requiring treatment will qualify as DLT. The classification for adverse events to be used is the following: 1. Mild adverse event; did not require treatment 2. Moderate adverse event; resolved with treatment 3. Severe adverse event; inability to carry on normal activities; required professional medical attention 4. Life-threatening or permanently disabling adverse event 5. Fatal adverse event In this grading system, "severe" is not equivalent to seriousness.

3 secondary outcomes

Muscle Function Measured by Six-minute Walk Test (6MWT)
Time frame: 2 years
Expression of Viral DNA (qPCR), and Follistatin Transgene in Muscle Tissue
Time frame: 180.days
Improvement of Muscle Function as Measured by North Star Ambulatory Assessment (NSAA)
Time frame: 2 years

Results and safety

Results posted to the registry on 15 Apr 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
2.4E12 vg/kg CMV.huFollistatin344	3	3

Primary outcome: Number of Dose Limiting Toxicity (DLT) Adverse Events as Assessed by 21 CFR 312.32.

Time frame: DLT Adverse events will be recorded from the date of dosing and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of dosing and for up to 2 years after gene therapy administration.. Number. Unit: Number of Events

Measure	2.4E12 vg/kg CMV.huFollistatin344 n = 3
Value	0

Population analysed: Safety Population: All subjects who receive a single total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events will be recorded from the date of informed consent and for up to 2 years after gene therapy administration, the subject's last study visit. Serious adverse events will be recorded from the date of informed consent and for up to 2 years after gene therapy administration, the subject's last study visit.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
2.4E12 vg/kg (1.2E12vg/kg/Limb) of rAAV1.CMV.huFollistatin344	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25322757Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM, Lowes LP, Alfano LN, Berry K, Meadows E, Lewis S, Braun L, Shontz K, Rouhana M, Clark KR, Rosales XQ, Al-Zaidy S, Govoni A, Rodino-Klapac LR, Hogan MJ, Kaspar BK. A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Mol Ther. 2015 Jan;23(1):192-201. doi: 10.1038/mt.2014.200. Epub 2014 Oct 17.
Background: PubMed 20368179Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall WR, Walker CM, Weisbrode SE, Janssen PM, Clark KR, Sahenk Z, Mendell JR, Kaspar BK. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med. 2009 Nov 11;1(6):6ra15. doi: 10.1126/scitranslmed.3000112.
Background: PubMed 19208403Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve. 2009 Mar;39(3):283-96. doi: 10.1002/mus.21244.
Background: PubMed 17164329Miller TM, Kim SH, Yamanaka K, Hester M, Umapathi P, Arnson H, Rizo L, Mendell JR, Gage FH, Cleveland DW, Kaspar BK. Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19546-51. doi: 10.1073/pnas.0609411103. Epub 2006 Dec 12.
Derived from this study: PubMed 40152935Bian X, Snow ZK, Zinn CJ, Gowan CC, Conley SM, Bratulin AL, Elhusseiny KM, Miller J, Tchkonia T, Kirkland JL, Lerman LO, Hickson LJ. Activin A Antagonism with Follistatin Reduces Kidney Fibrosis, Injury, and Cellular Senescence-Associated Inflammation in Murine Diabetic Kidney Disease. Kidney360. 2025 Mar 28;6(8):1278-1291. doi: 10.34067/KID.0000000776.
Click here for Center for Gene Therapy, The Research Institute at Nationwide Children's HospitalLink provided by the sponsor.

Related trials for Duchenne Muscular Dystrophy

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Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy
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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.

Jerry R Mendell, MD principal investigator

Director, Center for Gene Therapy, Nationwide Children's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing rAAV1.CMV.huFollistin344 in people with Duchenne Muscular Dystrophy, run by Jerry R. Mendell at 1 site 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 7 inclusion and 10 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 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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 15 Apr 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 Dose Limiting Toxicity (DLT) Adverse Events as Assessed by 21 CFR 312.32. (time frame: DLT Adverse events will be recorded from the date of dosing and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of dosing and for up to 2 years after gene therapy administration.). 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 NCT02354781, which also lists 5 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 11 Oct 2023.