Clinical trial NCT06641895: Evaluation of the Safety and Efficacy of BBM-D101 to Treat Patients with Duchenne Muscular Dystrophy
Official title: A Single-Arm, Open-Label, Single-Dose Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of BBM-D101 Injection in Patients with Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Duchenne Muscular Dystrophy (DMD)
Keywords: Adeno-Associated Virus
gene therapy
Duchenne muscular dystrophy
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai Mianyi Biopharmaceutical Co., Ltd.
First posted: 2024-10-15
Enrollment: 6
Sex: MALE
Minimum age (years): 4
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the safety, tolerability, and efficacy of BBM-D101 to treat patients with Duchenne Muscular Dystrophy.

Detailed description: This is a single-arm, open-label study to evaluate the safety, tolerability, efficacy, pharmacokinetic, pharmacodynamic, and immune response of BBM-D101 within 52 weeks after a single intravenous infusion in DMD boys, as well as the long-term safety and efficacy of BBM-D101 for up to 5 years post infusion.

BBM-D101 is gene addition therapy based on engineered AAV delivery therapeutic protein gene cassette into muscle for treating DMD. Therapeutic protein could mediate the dystrophin-associated protein complex to prevent muscular dystrophy and to rescue the function of muscle.

Eligibility criteria: Inclusion Criteria:

1. The legal guardian of the subject fully understands the purpose, nature, methods, and possible risks of the study, and signs a written informed consent form;
2. The study includes ambulatory male subjects who are at least 4 years old and less than 8 years old (4 years old ≤ age \&lt; 8 years old) ;
3. Genetically confirmed diagnosis of DMD;
4. Have at least 1 of the following typical clinical signs or laboratory abnormalities of DMD: proximal muscle weakness, waddling gait, pseudo gastrocnemius hypertrophy, Gower\&#39;s sign, pterygoid scapula;
5. Ability to cooperate with motor assessment testing, magnetic resonance imaging (MRI) and muscle biopsy according to the requirements of the study.

Exclusion Criteria:

1. Hepatitis B surface antigen (HBsAg) positive, hepatitis B virus deoxyribonucleic acid (HBV-DNA) ≥1000U/mL, hepatitis C virus ribonucleic acid (HCV-RNA) positive or human immunodeficiency virus (HIV) positive;
2. Receiving antiviral therapy for hepatitis B, hepatitis C, HIV, etc.;
3. Left ventricular ejection fraction (LVEF) \&lt;50% or ≥ class III cardiac function defined by New York Heart Association (NYHA);
4. With severe or persistent arrhythmias and congenital heart disease.
5. The subject\&#39;s preventive treatment/cardiomyopathy treatment changes within 1 month before the start of the study treatment;
6. With underlying liver disease, such as previous diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy, or hepatic fibrosis ≥ stage 3; or nodules, cysts found by B-ultrasound in the past, or elevated alpha-fetoprotein in laboratory tests during the screening period, etc., and these abnormalities are judged by the investigator to be clinically significant;

Primary outcomes:
measure: Incidence of dose limiting toxicity (DLT) events
timeFrame: 12 weeks
measure: The incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 52 weeks
Secondary outcomes:
measure: Changes from baseline in the North Star Ambulatory Assessment (NSAA)
timeFrame: 52 weeks
measure: Changes from baseline in the time to ascend 10-meter walk/run test (10MWR) without assistance
timeFrame: 52 weeks
measure: Changes from baseline in the time to ascend time to rise (TTR) without assistance without assistance
timeFrame: 52 weeks
measure: Changes from baseline in the time to ascend 4 steps (4-stair climb, 4SC) without assistance
timeFrame: 52 weeks
measure: Changes from baseline in the time to ascend 100-meter walk/run test (100MWR) without assistance
timeFrame: 52 weeks
measure: Changes from baseline in BBM-D101 genome copies in muscle biopsy samples
timeFrame: 52 weeks
measure: Changes from baseline in BBM-D101 therapeutic protein level in muscle biopsy samples
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Children's Medical Center, affiliated to Shanghai Jiao Tong University School of Medicine
name: Jiwen Wang
role: STUDY_CHAIR
References: