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Evaluation of the Safety and Efficacy of Hemophilia B Gene Therapy Drug

Phase 3
Active, not recruiting
Conditions
Hemophilia B
Interventions
Genetic: Single dose intravenous injection of BBM-H901
Registration Number
NCT05203679
Lead Sponsor
Shanghai Belief-Delivery BioMed Co., Ltd
Brief Summary

This is a multi-center, single-arm, open-label, single-dose treatment clinical study to evaluate the safety, tolerability and efficacy of BBM-H901 injection in Hemophilia B subjects with ≤2 International unit per deciliter (IU/dl) residual factor IX (FIX) levels.

BBM-H901 is an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene and raises circulating levels of endogenous FIX.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
32
Inclusion Criteria
  1. Males ≥ 18 years of age;
  2. Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels;
  3. Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subjects' records/histories;
  4. Have had bleeding events and/or injected with FIX protein products (including recombination and plasma source) during the last 12 weeks documented in the subjects' medical records;
  5. Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
  6. Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after administration.
Exclusion Criteria
  1. Being positive for hepatitis B surface antigen (HBsAg) or hepatitis B virus-DNA (HBV-DNA). Being positive for hepatitis C virus antibody (HCV-Ab) or hepatitis C virus RNA (HCV-RNA). Subjects with medical history of hepatitis B or C can be regarded as negative only when 2 required samplings are conducted at least 3 months apart and both test results of indicators aforementioned are negative, i.e. subjects with natural clearance and anti-viral therapy clearance for hepatitis B or C are eligible;
  2. Have potential liver diseases, such as previous diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy or liver fibrosis (fibrosis stage ≥ 3); nodules or cysts were found by B ultrasound, or elevated alpha-fetoprotein was detected by laboratory tests. Subjects who are not eligible for the study if the abnormalities are clinically significant regarding to the medical judgement of the investigator;
  3. HIV positive patients;
  4. Have participated in a previous gene therapy research trial before screening, or in a clinical study with an investigational drug within 5 half-life of the investigational product, whichever is longer;
  5. Have alcohol or drug dependence, or cannot stop drinking throughout the study;
  6. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm of BBM-H901Single dose intravenous injection of BBM-H9011×10\^13 vg/kg, Single-dose treatment
Primary Outcome Measures
NameTimeMethod
Annualized bleeding rate (ABR)52 weeks post-infusion

To assess ABR, including spontaneous bleeding and traumatic bleeding after administration.

Secondary Outcome Measures
NameTimeMethod
Mean FIX Padua Activity Level52 weeks post-infusion

Measurement of mean FIX Padua activity levels over the 52-week period following BBM-H901 injection.

Other FIX Protein Product Usage52 weeks post-infusion

Number and total volume of infusions of exogenous FIX protein products (recombinant or plasma-derived) administered within 52 weeks post-BBM-H901 injection.

Target Joint Count52 weeks post-infusion

Number of target joints recorded within 52 weeks post-BBM-H901 injection.

Joint Bleeding Episodes52 weeks post-infusion

Total number of joint bleeding events occurring within 52 weeks post-BBM-H901 injection.

Bleeding-Free Subjects52 weeks post-infusion

Proportion of subjects experiencing no bleeding events within 52 weeks post-BBM-H901 injection.

Adverse Event Incidence52 weeks post-infusion

Incidence of adverse events (AEs) and serious adverse events (SAEs) within 52 weeks post-BBM-H901 injection.

FIX Inhibitor Incidence52 weeks post-infusion

Incidence of FIX inhibitors measured by Bethesda or Nijmegen-Bethesda assays within 52 weeks post-BBM-H901 injection.

AAV Vector Shedding52 weeks post-infusion

Changes in AAV vector shedding in plasma, urine, semen, saliva, and PBMCs within 52 weeks post-BBM-H901 injection.

Trial Locations

Locations (9)

The Second People's Hospital of Shenzhen

🇨🇳

Shenzhen, Guangdong, China

Peking Union Medical College Hospital

🇨🇳

Beijing, Beijing, China

Anhui Provincial Hospital

🇨🇳

Hefei, Anhui, China

North China University of Science and Technology Affiliated Hospital

🇨🇳

Tangshan, Hebei, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

Nanfang Hospital Southern Medical University

🇨🇳

Guangzhou, Guangdong, China

The Second Hospital of Shanxi Medical University

🇨🇳

Taiyuan, Shanxi, China

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

🇨🇳

Tianjin, Tianjin, China

The second Affiliated Hospital of Kunming Medical University

🇨🇳

Kunming, Yunnan, China

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