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

Primary Purpose

Hemophilia B

Status

Active

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Single dose intravenous injection of BBM-H901

About this trial

This is an interventional treatment trial for Hemophilia B focused on measuring Hemophilia B;gene therapy;Adeno-Associated Virus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Males ≥ 18 years of age;
Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels;
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;
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;
Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after administration.

Exclusion Criteria:

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;
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;
HIV positive patients;
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;
Have alcohol or drug dependence, or cannot stop drinking throughout the study;
Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.

Sites / Locations

Anhui Provincial Hospital
Peking Union Medical College Hospital
Nanfang Hospital Southern Medical University
The Second People's Hospital of Shenzhen
North China University of Science and Technology Affiliated Hospital
Henan Cancer Hospital
The Second Hospital of Shanxi Medical University
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
The second Affiliated Hospital of Kunming Medical University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm of BBM-H901

Arm Description

1×10^13 vg/kg, Single-dose treatment

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicity (DLT) events.

To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) within 6 or 10 weeks after administration.

The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

To assess the safety of BBM-H901 Injection by TEAEs and SAEs.

Changes in liver function

To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT).

Secondary Outcome Measures

FIX activity

All samples collected from participants for plasma FIX activity levels were analyzed and used to determine peak and steady-state vector-derived circulating FIX activity levels.

FIX antigen level

To assess FIX antigen level within 52 weeks after administration.

The viral load of AAV vector

To assess the viral load of AAV vector within 52 weeks after administration.

Annualized bleeding rate (ABR)

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

Improvement in patient's quality of life

To assess the proportion of subjects with life improvement from baseline through Hemophilia Joint Health Score (HJHS), Hemophilic Early Arthropathy Detection with UltraSound in China (HEAD-US-C) and the Medical Outcomes Study (MOS) item short from health survey (SF-36) at 4, 12, 26 and 52 weeks.

Full Information

NCT ID

NCT05203679

First Posted

December 29, 2021

Last Updated

August 9, 2023

Sponsor

Shanghai Belief-Delivery BioMed Co., Ltd

1. Study Identification

Unique Protocol Identification Number

NCT05203679

Brief Title

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

Official Title

A Study to Evaluate the Safety, Tolerability and Efficacy of an Adeno-associated Virus Vector Containing an Expression Cassette of the Human Factor IX Transgene (BBM-H901) Injection in Patients With Hemophilia B

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 30, 2021 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

June 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Belief-Delivery BioMed Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hemophilia B

Keywords

Hemophilia B;gene therapy;Adeno-Associated Virus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm of BBM-H901

Arm Type

Experimental

Arm Description

1×10^13 vg/kg, Single-dose treatment

Intervention Type

Genetic

Intervention Name(s)

Single dose intravenous injection of BBM-H901

Intervention Description

Single dose intravenous infusion of BBM-H901, an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene in liver. The dose of BBM-H901 will be 1×10^13 vg/ kg

Primary Outcome Measure Information:

Title

Incidence of dose limiting toxicity (DLT) events.

Description

To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) within 6 or 10 weeks after administration.

Time Frame

6 or 10 weeks

Title

The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Description

To assess the safety of BBM-H901 Injection by TEAEs and SAEs.

Time Frame

52 weeks

Title

Changes in liver function

Description

Time Frame

52 weeks

Secondary Outcome Measure Information:

Title

FIX activity

Description

All samples collected from participants for plasma FIX activity levels were analyzed and used to determine peak and steady-state vector-derived circulating FIX activity levels.

Time Frame

52 weeks

Title

FIX antigen level

Description

To assess FIX antigen level within 52 weeks after administration.

Time Frame

52 weeks

Title

The viral load of AAV vector

Description

To assess the viral load of AAV vector within 52 weeks after administration.

Time Frame

52 weeks

Title

Annualized bleeding rate (ABR)

Description

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

Time Frame

52 weeks

Title

Improvement in patient's quality of life

Description

Time Frame

52 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males ≥ 18 years of age; Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels; 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; 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; Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration; Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after administration. Exclusion Criteria: 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; 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; HIV positive patients; 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; Have alcohol or drug dependence, or cannot stop drinking throughout the study; Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lei Zhang, MD

Organizational Affiliation

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

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Caifeng Yang, Master

Organizational Affiliation

Shanghai Belief-Delivery BioMed Co., Ltd

Official's Role

Study Director

Facility Information:

Facility Name

Anhui Provincial Hospital

City

Hefei

State/Province

Anhui

ZIP/Postal Code

230022

Country

China

Facility Name

Peking Union Medical College Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100005

Country

China

Facility Name

Nanfang Hospital Southern Medical University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510515

Country

China

Facility Name

The Second People's Hospital of Shenzhen

City

Shenzhen

State/Province

Guangdong

ZIP/Postal Code

518025

Country

China

Facility Name

North China University of Science and Technology Affiliated Hospital

City

Tangshan

State/Province

Hebei

ZIP/Postal Code

063000

Country

China

Facility Name

Henan Cancer Hospital

City

Zhengzhou

State/Province

Henan

ZIP/Postal Code

450003

Country

China

Facility Name

The Second Hospital of Shanxi Medical University

City

Taiyuan

State/Province

Shanxi

ZIP/Postal Code

030001

Country

China

Facility Name

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

City

Tianjin

State/Province

Tianjin

ZIP/Postal Code

300020

Country

China

Facility Name

The second Affiliated Hospital of Kunming Medical University

City

Kunming

State/Province

Yunnan

ZIP/Postal Code

650032

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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