Evaluation of the Safety and Efficacy of BBM-D101 to Treat Patients with Duchenne Muscular Dystrophy

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

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

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Genetic: BBM-D101

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.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jiwen Wang; Phone Number: 18916613192; Email: wangjiwen@scmc.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine
      • Contact: Jiwen Wang; Phone Number: 18916613192; Email: wangjiwen@scmc.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 < 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'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) <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'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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose intravenous injection of BBM-D101	Genetic: BBM-D101; BBM-D101 is a recombinant adeno-associated virus vector-based gene therapy for DMD treatment. It is a suspension for single intravenous (IV) infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicity (DLT) events	To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after BBM-D101 injection infusion.	12 weeks
The incidence of adverse events (AEs) and serious adverse events (SAEs)	To assess the safety of BBM-D101 Injection by AEs and SAEs.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in the North Star Ambulatory Assessment (NSAA)	To assess changes in NSAA from baseline within 12 weeks, 26 weeks, and 52 weeks after BBM-D101 injection infusion; The NSAA is a scale that rates performance of various motor abilities in ambulant children with Duchenne Muscular Dystrophy and is used to monitor disease progression and treatment effects. The NSAA total score is defined as the sum of all 17items, ranging from 0 (worst) to 34 (best).	52 weeks
Changes from baseline in the time to ascend 10-meter walk/run test (10MWR) without assistance	To assess changes in 10MWR from baseline within 12 weeks, 26 weeks, and 52 weeks after BBM-D101 injection infusion	52 weeks
Changes from baseline in the time to ascend time to rise (TTR) without assistance without assistance	To assess changes in TTR from baseline within 12 weeks, 26 weeks, and 52 weeks after BBM-D101 injection infusion	52 weeks
Changes from baseline in the time to ascend 4 steps (4-stair climb, 4SC) without assistance	To assess changes in 4-SC from baseline within 12 weeks, 26 weeks, and 52 weeks after BBM-D101 injection infusion	52 weeks
Changes from baseline in the time to ascend 100-meter walk/run test (100MWR) without assistance	To assess changes in 100MWR from baseline within 12 weeks, 26 weeks, and 52 weeks after BBM-D101 injection infusion	52 weeks
Changes from baseline in BBM-D101 genome copies in muscle biopsy samples	To assess changes of BBM-D101 genome from baseline in muscle in 12 weeks and 52 weeks following BBM-D101 administration. BBM-D101 genome was detected by Quantitative Polymerase Chain Reaction (QPCR).	52 weeks
Changes from baseline in BBM-D101 therapeutic protein level in muscle biopsy samples	To assess changes of BBM-D101 therapeutic protein from baseline in muscle in 12 weeks and 52 weeks following BBM-D101 administration. BBM-D101 therapeutic protein was detected by western blot (Jess) and tissue immunofluorescence.	52 weeks

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Shanghai Mianyi Biopharmaceutical Co., Ltd.
• Investigators: Study Chair: Jiwen Wang, Shanghai Children's Medical Center, affiliated to Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2030

Study Registration Dates

• First Submitted: October 8, 2024
• First Submitted That Met QC Criteria: October 14, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 23, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: gene therapy; Duchenne muscular dystrophy; Adeno-Associated Virus
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: BBM041-IIT1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No