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

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ClinicalTrials.gov Identifier: NCT02354781
Recruitment Status : Completed
First Posted : February 3, 2015
Results First Posted : April 15, 2020
Last Update Posted : April 15, 2020
Sponsor:
Collaborators:
Duchenne Alliance
Milo Therapeutics
Information provided by (Responsible Party):
Jerry R. Mendell, Nationwide Children's Hospital

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Duchenne Muscular Dystrophy
Intervention Biological: rAAV1.CMV.huFollistin344
Enrollment 3
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 2.4E12 vg/kg CMV.huFollistatin344
Hide Arm/Group Description Participants enrolled will receive a single dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344 delivered to the lower limbs
Period Title: Overall Study
Started 3
Completed 3
Not Completed 0
Arm/Group Title Dose Group 1
Hide Arm/Group Description Participants enrolled will receive a single dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344 delivered to the lower limbs
Overall Number of Baseline Participants 3
Hide Baseline Analysis Population Description
The Safety Population included all subjects who received one dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344. The Safety Population is the primary analysis population for safety assessments
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
<=18 years
3
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
Female
0
   0.0%
Male
3
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
3
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
3
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants
3
1.Primary Outcome
Title Number of Dose Limiting Toxicity (DLT) Adverse Events as Assessed by 21 CFR 312.32.
Hide Description

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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: All subjects who receive a single total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.
Arm/Group Title 2.4E12 vg/kg CMV.huFollistatin344
Hide Arm/Group Description:
Participants enrolled who receive a total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: Number of Events
0
2.Secondary Outcome
Title Muscle Function Measured by Six-minute Walk Test (6MWT)
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants enrolled will receive a single dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344 delivered to the lower limbs
Arm/Group Title 2.4E12 vg/kg CMV.huFollistatin344
Hide Arm/Group Description:
Participants enrolled will receive a total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344 delivered to the lower limbs
Overall Number of Participants Analyzed 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Secondary Outcome
Title Expression of Viral DNA (qPCR), and Follistatin Transgene in Muscle Tissue
Hide Description

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)

Time Frame 180.days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants enrolled will receive a single dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344 delivered to the lower limbs
Arm/Group Title 2.4E12 vg/kg CMV.huFollistatin344
Hide Arm/Group Description:
Participants enrolled who receive a total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.
Overall Number of Participants Analyzed 3
Measure Type: Count of Participants
Unit of Measure: Participants
1
  33.3%
4.Secondary Outcome
Title Muscle Function Measured by North Star Ambulatory Assessment (NSAA)
Hide Description

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.

Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants enrolled who receive a single dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.
Arm/Group Title 2.4E12 vg/kg CMV.huFollistatin344
Hide Arm/Group Description:
Participants enrolled who receive a total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.
Overall Number of Participants Analyzed 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 2.4E12 vg/kg (1.2E12vg/kg/Limb) of rAAV1.CMV.huFollistatin344
Hide Arm/Group Description Participants enrolled will receive a total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344 delivered to the lower limbs
All-Cause Mortality
2.4E12 vg/kg (1.2E12vg/kg/Limb) of rAAV1.CMV.huFollistatin344
Affected / at Risk (%)
Total   0/3 (0.00%)    
Hide Serious Adverse Events
2.4E12 vg/kg (1.2E12vg/kg/Limb) of rAAV1.CMV.huFollistatin344
Affected / at Risk (%) # Events
Total   1/3 (33.33%)    
Injury, poisoning and procedural complications   
Head Injury From Fall   1/3 (33.33%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
2.4E12 vg/kg (1.2E12vg/kg/Limb) of rAAV1.CMV.huFollistatin344
Affected / at Risk (%) # Events
Total   3/3 (100.00%)    
Eye disorders   
Stye   1/3 (33.33%)  1
Gastrointestinal disorders   
GERD   1/3 (33.33%)  1
Constipation   1/3 (33.33%)  1
Infections and infestations   
Influenza   1/3 (33.33%)  1
Injury, poisoning and procedural complications   
Pain   3/3 (100.00%)  5
Compression Fracture   1/3 (33.33%)  1
Musculoskeletal and connective tissue disorders   
Increased Muscle Weakness   1/3 (33.33%)  1
Psychiatric disorders   
Anxiety   1/3 (33.33%)  2
Behavioral Changes/Agitation   1/3 (33.33%)  1
Insomnia   1/3 (33.33%)  1
Respiratory, thoracic and mediastinal disorders   
Pharyngitis   1/3 (33.33%)  1
Rhinorrhea   1/3 (33.33%)  1
Nasal congestion   1/3 (33.33%)  1
Skin and subcutaneous tissue disorders   
Abrasion   1/3 (33.33%)  2
Bruising   2/3 (66.67%)  3
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Jerry Mendell
Organization: Nationwide Children's Hospital
Phone: 1-614-722-4877
EMail: Jerry.Mendell@nationwidechildrens.org
Layout table for additonal information
Responsible Party: Jerry R. Mendell, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT02354781    
Other Study ID Numbers: 14-00630
First Submitted: January 26, 2015
First Posted: February 3, 2015
Results First Submitted: January 24, 2020
Results First Posted: April 15, 2020
Last Update Posted: April 15, 2020