Gene Therapy for Chinese Hemophilia B

NCT04135300 | Completed DMC

• 1 other identifier: GT2019001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

GT2019001 is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and kinetics of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels. BBM-H901 is an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene and raise circulating levels of endogenous FIX.

Conditions

Hemophilia B

Keywords

Hemophilia B; gene therapy; ADENO-ASSOCIATED VIRUSES

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment- related adverse events

  Number of patients experiencing treatment-related adverse events. Including inhibitor development.

  Infusion to the end of study, average 1 year.

• Change from baseline alanine aminotransferase ans aspartate amino transferase

  liver function tests include ALT, AST.

  At multiple timepoints from pre-dose through up to 1 years post-dose

• Antibody against AAV capsid protein

  Immune response against AAV capsid will be evaluated by measurement of the total antibody and neutralizing antibody against AAV capsid protein in plasma samples collected at multiple timepoints after dosing up to 1 year.

  from screening through up to 1 years

Secondary Outcomes (1)

• Vector- derived FIX:C and FIX antigen levels.

  At multiple timepoints from pre-dose through up to 1 years post-dose

Other Outcomes (4)

• Vector shedding of BBM-H901

  From date of infusion until the date of 3 consecutive documented negative results, assessed up to 1 year

• annualized bleeding rate changes from baseline

  through study completion, an average of 1 year

• Long- term vector derived factor IX activity level

  Up to twenty years after gene transfer

Study Arms (1)

Arm of BBM-H901

EXPERIMENTAL

Subjects will be dosed with single dose of BBM-H901 at 5x10·12 vg/kg via intravenous infusion.

Genetic: Single dose intravenous injection of BBM-H901

Interventions

Single dose intravenous injection of BBM-H901 GENETIC

Single dose intravenous infusion of BBM-H901, an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene in liver. The dose of BBM-H901 will be 5x10'12 vg/Kg.

Arm of BBM-H901

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations;
• Be male and ≥18 years of age;
• Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels as documented by a certified clinical laboratory at the time of screening. If the screening result is \>2% due to insufficient washout from FIX protein product, then the severity of hemophilia B may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤2% FIX coagulant activity (FIX:C) ;
• Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subject's record/history;
• a. Prophylaxis subjects: have had bleeding events and/or infusions with FIX protein products during the last 12 weeks documented in the subjects' medical records; OR b. On-demand subjects: have had ≥4 bleeding events in the last 52 weeks and/or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints;
• Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
• Have no measurable FIX inhibitor as assessed by laboratory; or documented no prior history of FIX inhibitor after 50 EDs (family history of inhibitors will not exclude the subject) and no clinical signs or symptoms of decreased response to FIX administration;
• Have acceptable laboratory values:
• Hemoglobin ≥11 g/dL;
• Platelets ≥100,000 cells/μL;
• AST, ALT, alkaline phosphatase ≤2x upper limit of normal at the testing laboratory;
• Bilirubin ≤3x ULN ;
• Creatinine ≤2.0 mg/dL.
• Agree to use reliable barrier contraception until 52 weeks and semen samples after the administration of BBM- H901 are negative for vector sequences.

You may not qualify if:

• Have active hepatitis B or C, and HBsAg, hepatitis B core antibody, hepatitis B virus-DNA positivity or hepatitis C virus-RNA viral load positivity, respectively. Negative viral assays in two samples, collected at least six months apart, will be required to be considered negative. Both natural clearers and those who have cleared hepatitis C virus on antiviral therapy are eligible;
• Currently on antiviral therapy for hepatitis B or C;
• Have significant underlying liver disease, as defined by a preexisting diagnosis of portal hypertension, splenomegaly, encephalopathy, reduction below normal limits of serum albumin or evidence of significant liver fibrosis (fibrosis stage ≥ 3) within the past 6 months prior to or at Screening as determined by any of the following diagnostic modalities: AST-to-Platelet Ratio Index (APRI) \>1;
• Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3. Subjects who are HIV-positive and stable, with an adequate CD4 count (\>200/mm3) and undetectable viral load (\<50 gc/mL) measured twice in the six months prior to enrollment, on an antiretroviral drug regimen are eligible to enroll;
• Have anti-BBM-H901 neutralizing antibody titers ≥1:5;
• Have history of chronic infection or other chronic disease that the Investigator considers to constitute an unacceptable risk;
• Have participated in a previous gene therapy research trial within the last 52 weeks or in a clinical study with an investigational drug within the last 12 weeks;
• Any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study;
• Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• East China University of Science and Technology: collaborator

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (1)

• Xue F, Li H, Wu X, Liu W, Zhang F, Tang D, Chen Y, Wang W, Chi Y, Zheng J, Du Z, Jiang W, Zhong C, Wei J, Zhu P, Fu R, Liu X, Chen L, Pei X, Sun J, Cheng T, Yang R, Xiao X, Zhang L. Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. 2022 Jul;9(7):e504-e513. doi: 10.1016/S2352-3026(22)00113-2. Epub 2022 May 19.

  PMID: 35598604 DERIVED

MeSH Terms

Conditions

Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Lei Zhang, MD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Hemophilia B patients

Study Record Dates

• First Submitted: October 8, 2019
• First Posted: October 22, 2019
• Study Start: October 16, 2019
• Primary Completion: January 7, 2022
• Study Completion: January 7, 2022
• Last Updated: February 21, 2025

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: From 12 months 36 months after study completion.
• Access Criteria: Upon request to PI.

Locations

CN (1)