Trial Outcomes & Findings for Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy (NCT NCT02354781)

Last Updated: 2023-10-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

3 participants

Primary outcome timeframe

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.

Results posted on

2023-10-11

Participant Flow

Participant milestones

Participant milestones
Measure	2.4E12 vg/kg CMV.huFollistatin344 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 Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Group 1 n=3 Participants 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
Age, Categorical <=18 years	3 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	3 participants n=93 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	2.4E12 vg/kg CMV.huFollistatin344 n=3 Participants Participants enrolled who receive a total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.
Number of Dose Limiting Toxicity (DLT) Adverse Events as Assessed by 21 CFR 312.32.	0 Number of Events

SECONDARY outcome

Timeframe: 2 years

Population: 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

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.

Outcome measures

Outcome measures
Measure	2.4E12 vg/kg CMV.huFollistatin344 n=3 Participants Participants enrolled who receive a total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.
Muscle Function Measured by Six-minute Walk Test (6MWT)	0 Participants

SECONDARY outcome

Timeframe: 180.days

Population: All muscle biopsies were canceled per PI discretion due to the disease progression of each participant.

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)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Participants enrolled who receive a single dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.

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.

Outcome measures

Outcome measures
Measure	2.4E12 vg/kg CMV.huFollistatin344 n=3 Participants Participants enrolled who receive a total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) of rAAV1.CMV.huFollistatin344.
Improvement of Muscle Function as Measured by North Star Ambulatory Assessment (NSAA)	1 Participants

Adverse Events

2.4E12 vg/kg (1.2E12vg/kg/Limb) of rAAV1.CMV.huFollistatin344

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	2.4E12 vg/kg (1.2E12vg/kg/Limb) of rAAV1.CMV.huFollistatin344 n=3 participants at risk 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
Injury, poisoning and procedural complications Head Injury From Fall	33.3% 1/3 • Number of events 1 • 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

Other adverse events
Measure	2.4E12 vg/kg (1.2E12vg/kg/Limb) of rAAV1.CMV.huFollistatin344 n=3 participants at risk 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
Injury, poisoning and procedural complications Pain	100.0% 3/3 • Number of events 5 • 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.
Respiratory, thoracic and mediastinal disorders Pharyngitis	33.3% 1/3 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	33.3% 1/3 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders Abrasion	33.3% 1/3 • Number of events 2 • 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.
Psychiatric disorders Anxiety	33.3% 1/3 • Number of events 2 • 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.
Psychiatric disorders Behavioral Changes/Agitation	33.3% 1/3 • Number of events 1 • 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.
Psychiatric disorders Insomnia	33.3% 1/3 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders Bruising	66.7% 2/3 • Number of events 3 • 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.
Gastrointestinal disorders GERD	33.3% 1/3 • Number of events 1 • 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.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • 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.
Eye disorders Stye	33.3% 1/3 • Number of events 1 • 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.
Musculoskeletal and connective tissue disorders Increased Muscle Weakness	33.3% 1/3 • Number of events 1 • 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.
Injury, poisoning and procedural complications Compression Fracture	33.3% 1/3 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Nasal congestion	33.3% 1/3 • Number of events 1 • 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.
Infections and infestations Influenza	33.3% 1/3 • Number of events 1 • 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.

Additional Information

Dr. Jerry Mendell

Nationwide Children's Hospital

Phone: 1-614-722-4877

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place