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

ConditionHemophilia B

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexMale

Age12-18

SponsorInstitute of Hematology & Blood Diseases Hospital, China

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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;

Trial design

Design model

Single group

Treatments tested in this trial

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.

Treatment groups

9 Participants

are divided into 1 treatment group

Group A: BBM-H901 administration groupExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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)

Time frame

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.

Time frame

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

Time frame

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

Time frame

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

Secondary outcomes

Vector shedding after BBM-H901 infusion

Vector genome in plasma, urea, stool, saliva will be monitored

Time frame

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

Vector derived Factor IX(FIX) activity

FIX:C measured using one- stage APTT based method

Time frame

infusion to 52 weeks after gene therapy

Annualized bleeding rate(ABR) after gene therapy

ABR will be prospectively collected at each visit.

Time frame

vector infusion to 52 weeks after gene therapy

Times of infusion of factor IX agents

Times of infusion of factor IX agents, eg FIX concentrates, prothrombin complex concentrate, fresh- frozen plasma.

Time frame

vector infusion to 52 weeks after gene therapy

Other outcomes

Long term factor IX activity

factor IX activity will be measured using one stage APTT based method

Time frame

52 weeks after gene therapy to up to 10 years

Long term Annualized bleeding rate

Annualized bleeding rate will be calculated based on the bleeding times and time interval

Time frame

52 weeks after gene therapy to up to 10 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institute of Hematology & Blood Diseases Hospital, China

Lead sponsor

Source ClinicalTrials.gov

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