Safety and Tolerability of VGB-R04 in Patients With Haemophilia B

NCT05152732 | Recruiting Early Phase 1

• 1 other identifier: IIT2021043
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

An Open-Label, Non-Randomized, uncontrolled, single-dose pilot study of VGB-R04 in subjects with Hemophilia B.

Conditions

Hemophilia B

Keywords

Hemophilia; AAV; safety; gene therapy

Outcome Measures

Primary Outcomes (5)

• Incidence of adverse events

  An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment.

  Baseline up to Week 52

• Incidence of serious adverse events

  A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening; require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect

  Baseline up to Week 52

• Number of Participants with Clinically Significant Change from Baseline in Vital Signs

  Vital signs (temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure) will be obtained with participants in the seated position, after having sat calmly for at least 5 minutes. The clinical significance of vital signs will be determined at the investigator's discretion

  Baseline up to Week 52

• Number of Participants with Clinically Significant Change From Baseline in Physical Examination Findings

  The physical examination will include examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination will assess the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings will be considered to be clinically significant based on the investigator's decision

  Baseline up to Week 52

• Number of Participants with Clinical Laboratory Abnormalities

  Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings were considered to be clinically significant based on the investigator's decision.

  Baseline up to Week 52

Secondary Outcomes (6)

• Vector- derived FIX:C Activity

  Baseline up to Week 52

• Vector- derived FIX antigen levels

  Baseline up to Week 52

• Annualized bleeding rate changes from baseline

  Baseline up to Week 52

• Annualized FIX consumption changes from baseline

  Baseline up to Week 52

• Number of target joints

  Baseline up to Week 52

Study Arms (1)

VGB-R04

EXPERIMENTAL

Single intravenous (i.v.) infusion of VGB-R04 Intervention: Gene Therapy / Gene Transfer

Genetic: VGB-R04

Interventions

VGB-R04 GENETIC

A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant

VGB-R04

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male ≥18 years and ≤75years of age;
• Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal or documented history of FIX activity ≤2%);
• At least 100 days exposure history to FIX;
• Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding;
• Have acceptable laboratory values:
• Hemoglobin ≥110 g/L;
• Platelets ≥100×10'9 cells/L;
• AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory;
• Bilirubin ≤3× ULN ;
• Creatinine ≤1.5× ULN.
• No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein;
• Agree to use reliable barrier contraception until 3 consecutive samples are negative for vector sequences;
• Able to provide informed consent and comply with the requirements of the study.

You may not qualify if:

• Have significant underlying liver disease within the past 6 months prior to or at Screening, including but not limited to:
• Preexisting diagnosis of portal hypertension;
• Splenomegaly;
• Encephalopathy;
• Reduction of serum albumin;
• Evidence of significant liver fibrosis;
• Have anti-VGB-R04 neutralizing antibody titers ≥1:5;
• Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.;
• Evidence of active hepatitis B virus infection (HBV-DNA \>103 IU/ml) or hepatitis C virus infection (HCV antigen and HCV-RNA positive);
• Evidence of malignant tumours or those with a previous history of malignant tumours;
• Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;
• Any immunodeficiency;
• Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational drug within the last 4 weeks;
• Have used glucocorticoids, immunosuppressive drugs, or antipsychotics within the last 3 months;
• Previous history of hypersensitivity or allergic reaction to any FIX products or any immunoglobulin;

Sponsors & Collaborators

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

Study Sites (1)

Blood diseases hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Hemophilia B; Hemophilia A

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, Doctor

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lei Zhang, Doctor

CONTACT

+86-13502118379; zhanglei1@ihcams.as.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: December 10, 2021
• Study Start: December 28, 2021
• Primary Completion: March 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 21, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: IPD will be shared with other researchers when VGB-R04 is fully approved.
• Access Criteria: IPD will be shared with other researchers when VGB-R04 is fully approved.

Locations

CN (1)