Gene Therapy for Hemophilia B Patients Aged 12-18 Years Old

NCT05709288 | Recruiting Phase 1 DMC

• 1 other identifier: IIT2022051
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels and aged 12-18 years old. 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

gene therapy; AAV

Outcome Measures

Primary Outcomes (4)

• The incidence of treatment related adverse events deemed related to BBM-H901 within 10 weeks after vector administration

  the type and incidence of TRAE after BBM-H901 infusion according to the CTCAE(v5.0)

  infusion to 10 weeks after vector infusion.

• The incidence of adverse events and serious adverse events within 52 weeks after BBM-H901 administration

  Number of patients experiencing treatment-related adverse events from vector infusion to 52 weeks after vector infusion.

  Vector infusion to 52 weeks after gene therapy.

• Change from baseline aspartate amino transferase

  number of subjects with elevation of AST. Number of episodes of elevating AST

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

• Change from baseline alanine aminotransferase

  number of subjects with elevation of ALT. Number of episodes of elevating ALT

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

Secondary Outcomes (6)

• Vector shedding after BBM-H901 infusion

  multiple timepoints until 2 consecutive negative results achieved usually within 52 weeks

• Vector derived Factor IX(FIX) activity

  infusion to 52 weeks after gene therapy

• Annualized bleeding rate(ABR) after gene therapy

  vector infusion to 52 weeks after gene therapy

• Times of infusion of factor IX agents

  vector infusion to 52 weeks after gene therapy

• number of target joint

  vector infusion to 52 weeks after gene therapy

Other Outcomes (2)

• Long term factor IX activity

  52 weeks after gene therapy to up to 10 years

• Long term Annualized bleeding rate

  52 weeks after gene therapy to up to 10 years

Study Arms (1)

BBM-H901 administration group

EXPERIMENTAL

Subjects will be administered with single dose intravenous infusion of BBM-H901.

Drug: BBM-H901

Interventions

BBM-H901 DRUG

Single dose intravenous infusion of BBM-H901, an adeno-associated viral (AAV) vector designed to drive expression of an hyper active human factor IX mutant(FIX Padua) transgene in liver. The dose of BBM-H901 is 5x10'12 vg/Kg.

BBM-H901 administration group

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects and statutory guardian must be able to understand the purpose and risks of the study and provide signed and dated informed consent;
• Be male and 12≤ age \<18 years of age, body wight ≥ 50kg;
• 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) ;
• Had had ≥75 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subject's record/history;
• With ≤ 1:4 neutralizing antibodies and ≤1:200 binding antibodies against BBM-H901 capsid;
• Subjects with bleeding episode and/ or FIX agents infusion events within 12 weeks prior to screening;
• 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 (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 ≤1.5x upper limit of normal at the testing laboratory;
• Bilirubin ≤1.5x ULN ;
• glomerular filtration rate eGFR ≥ 60ml/min.
• For those subjects with sexual maturity, subject and statutory guardian must know that subjects must agree to use reliable barrier contraception until 52 weeks;

You may not qualify if:

• Hepatitis B surface antigen antibody (HBSAg-Ab) or HBV-DNA positive; hepatitis C antibody or HCV-RNA positive;
• Currently on antiviral therapy for hepatitis B or C;
• With coagulation disorders other than hemophilia B;
• Had immunosuppressive therapy other than steroid and other suggested IST agents within 30 days prior to screening;
• Had vaccine 30 days prior to screening or have scheduled vaccination plan during the study (up to 52 weeks);
• Have significant underlying liver disease, as defined by a preexisting diagnosis of portal hypertension, splenomegaly, encephalopathy, etc; other liver conditions unsuitable to gene therapy judged by investigator;
• Have surgery plan within 52 weeks after gene therapy;
• Have history of chronic infection or high rish of infection that the Investigator considers to constitute an unacceptable risk;
• Had 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;
• Had any herb that may affect the liver function within 4 weeks prior to screening;
• Have history of fatal bleeding episode, eg intracranial hemorrhage, etc;
• 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;

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of haematology and Blood diseases hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

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

  Insitute of haematology and blood diseases hospital, chinese academy of medical sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Xue, MD

CONTACT

+862223909240; xuefeng@ihcams.ac.cn

Shuo Chen, BS

CONTACT

+862223909009; Chenshuo@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: January 19, 2023
• First Posted: February 2, 2023
• Study Start: March 23, 2023
• Primary Completion (Estimated): June 1, 2035
• Study Completion (Estimated): November 1, 2035
• Last Updated: February 21, 2025

Record last verified: 2025-01

Data Sharing

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

Locations

CN (1)