Gene Therapy for Chinese Hemophilia A

NCT04728841 | Recruiting

• 1 other identifier: IIT2020030
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

IHBDH-GTHA-2020 is an open- label, non- randomized study to evaluate the safety, tolerability and kinetics of a single intravenous infusion of GS001 in hemophilia A subjects with \<1 IU/dl residual FVIII levels.

Conditions

Hemophilia A; Gene Therapy

Outcome Measures

Primary Outcomes (8)

• Incidence of treatment- related adverse events

  Number of patients experiencing treatment-related adverse events.

  From screening through up to the end of study (about 5 years).

• Percentage of subjects in each dose group with newly occurred clinically significant abnormalities in physical examination compared to the baseline.

  The number of subjects in each dose group with clinically significant changes in physical examination compared to the baseline.

  From the start of study treatment (Day 1) through up to the end of study (about 5 years).

• Changes of Weighted Mean of vital signs (systolic blood pressure [SBP] and diastolic blood pressure [DBP], pulse rate, temperature, respiratory rate) from baseline at each assessment time point for each dose group

  The vital signs (SBP, DBP, pulse rate, temperature, respiratory rate) of the subjects were measured. The maximum, minimum, and mean observed values of vital signs (SBP, DBP, pulse rate, temperature, respiratory rate) from the dosing (Day 1) to the end of the study were calculated for each subject.

  From the start of study treatment (Day 1) through up to the end of study (about 5 years).

• Changes of Mean Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amio Transferase (AST) from baseline at each assessment time point for each dose group

  Blood samples of subjects were collected for the evaluation of liver function throughout this study. All of these parameters are measured to help assess the condition of the liver. For ALP, AST and ALT, the percentage of subjects with the worst post-treatment results in each dose group will be summarized as follows: \> 1.0 x ULN ≤ 1.5x ULN; \> 1.5 x ULN ≤ 3.0 x ULN; \> 3.0 x ULN ≤ 5.0 x ULN; \> 5.0 x ULN

  From the start of study treatment (Day 1) through up to the end of study (about 5 years).

• Immune response to AAV capsid proteins

  Changes in the expression levels of neutralizing and binding antibodies of AAV.

  From screening period through up to 5 years.

• Immune response to FVIII transgene

  The changes of FVIII inhibitor and antibody levels

  From screening period through up to 5 years.

• Viral vector shedding of GS001

  The vector shedding in serum, PMBC, saliva, urine, semen and feces will be monitored

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

• Thrombosis risk assessment

  For any individual who reaches \>150% vector-derived FVIII: C activity levels following the infusion of GS001, laboratory parameters of thrombotic potential will be assessed.

  From the start of study treatment (Day 1) through up to the end of study (about 5 years).

Secondary Outcomes (4)

• Vector- derived FVIII:C and FVIII antigen levels

  From pre-dose phase through up to 1 years post-dose

• FVIII usage within 1 year after GS001 infusion

  From week 3 to week 52 post GS001 infusion.

• Number of bleeding events requiring exogenous FVIII replacement therapy within 1 year after GS001 infusion

  Week 3 to Week 52 post GS001 Infusion

• Number of bleeding events within 1 year after GS001 infusion

  Week 3 to Week 52 post GS001 infusion

Other Outcomes (8)

• Long-term FVIII: C activity Level

  From year 2 to year 5 post GS001 infusion.

• Annualized number of bleeding episodesrequiring exogenous FVIII replacement therapy during long-term follow up.

  From year 2 to year 5 post GS001 infusion.

• Total utilization of FVIII replacement therapy (IU/kg) per year for long-term follow up.

  From year 2 to year 5 post GS001 infusion.

Study Arms (1)

Treatment group

EXPERIMENTAL

Arm of GS001

Genetic: Injection of GS001

Interventions

Injection of GS001 GENETIC

Patients will be enrolled sequentially every 3 weeks or more between cohorts. Dose escalation may occur after a single patient has been safely dosed if the resulting FVIII activity at Week 3 is \< 5 IU/dL.The dose levels are as follows: 1. 2×10\^12 vg/kg 2. 6×10\^12vg/kg or other recommended doses 3. 2×10\^13 vg/kg or other recommended doses

Treatment group

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 informed consent according to national and local privacy laws;
• Male subjects and ≥ 18 years of age;
• Have hemophilia A with ≤1 IU/dL (≤1%) endogenous FVIII activity levels at the time of screening. If the screening result is \>1% due to previous treatment with FVIII product, then it may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤1% FVIII activity levels ;
• No history of hypersensitivity or anaphylaxis associated with FVIII product administration;
• Have no measurable FVII inhibitor as assessed by laboratory two times that were at least one week apart; or documented no prior history of FVIII inhibitor after 150 EDs and no clinical signs or symptoms of decreased response to FVIII infusion ;
• Have acceptable laboratory values sampled at screening and repeated prior to Day 0; A. Hemoglobin ≥ 11 g/dL; B. Platelets ≥ 100 x 10\^9/L; C. AST, ALT, alkaline phosphatase ≤ 1.25 upper limit of normal (ULN); D. Bilirubin ≤ 1.25 ULN; E. Creatinine ≤ 2 mg/dL.
• Agree to use reliable barrier contraception until the end of the 52 weeks observation period, and three consecutive semen samples are negative for vector sequences after GS001 infusion.

You may not qualify if:

• Have Hepatitis B, hepatitis C or HBsAg, HCVAb, HBV-DNA, HCV-RNA are positive and have clinical significance. Both natural clearers and those who have cleared HCV on antiviral therapy are deemed eligible;
• Currently Receiving antiviral therapy for hepatitis B and C;
• Have history of chronic infections or other chronic diseases that may pose a risk to the study participation;
• 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 past 30 days;
• The subject has any concurrent diseases that cannot tolerate treatments of prednisone or prednisolone as judged by the investigator;
• History of arterial or venous thromboembolic events (e.g., deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolism);
• Known inherited or acquired thrombophilia, including conditions associated with increased risk of thromboembolism, such as atrial fibrillation;
• Major surgery planned in 1 year period following the infusion with GS001;
• Hypersensitivity to the study vector;
• Have clinically major diseases or any other unspecified conditions that, in the opinion of the Investigator, makes the subject unsuitable for participating in the study;
• Patients who are unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;
• Evidence of other bleeding disorders not associated with hemophilia A.

Sponsors & Collaborators

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

Study Sites (1)

Chinese Academy of Medical Science and Blood Disease Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

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

Study Officials

• Lei Zhang, MD

  Chinese Academy of Medical Science and Blood Disease Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Liu, MD

CONTACT

+82223909240; liuwei1@ihcams.ac.cn

Lei Zhang, MD

CONTACT

+82223909240; zhanglei1@ihcams.ac.cn

Study Design

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

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 28, 2021
• Study Start: March 4, 2021
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: August 1, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)