Clinical Trials in China / NCT04728841
Recruiting
Not applicable
Gene Therapy for Chinese Hemophilia A
NCT04728841 · tracked via the Priya Life Science China tracker
Condition(s) studied
Hemophilia AGene Therapy
Investigational drug(s) / intervention(s)
Injection of GS001
Injection of GS001: 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
Study 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.
Eligibility
Inclusion Criteria:
1. Be able to understand the purpose and risks of the study and provide informed consent according to national and local privacy laws;
2. Male subjects and ≥ 18 years of age;
3. 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 ;
4. No history of hypersensitivity or anaphylaxis associated with FVIII product administration;
5. 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 ;
6. 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.
7. 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.
Exclusion Criteria:
1. 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;
2. Currently Receiving antiviral therapy for hepatitis B and C;
3. Have history of chronic infections or other chronic diseases that may pose a risk to the study participation;
4. 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;
5. The subject has any concurrent diseases that cannot tolerate treatments of prednisone or prednisolone as judged by the investigator;
6. History of arterial or venous thromboembolic events (e.g., deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolism);
7. Known inherited or acquired thrombophilia, including conditions associated with increased risk of thromboembolism, such as atrial fibrillation;
8. Major surgery planned in 1 year period following the infusion with GS001;
9. Hypersensitivity to the study vector;
10. 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;
11. Patients who are unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;
12. Evidence of other bleeding disorders not associated with hemophilia A.
Primary outcome measure(s)
- Incidence of treatment- related adverse events — From screening through up to the end of study (about 5 years).
Number of patients experiencing treatment-related adverse events. - Percentage of subjects in each dose group with newly occurred clinically significant abnormalities 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).
The number of subjects in each dose group with clinically significant changes in physical examination compared to the baseline. - 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 — From the start of study treatment (Day 1) through up to the end of study (about 5 years).
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. - 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 — From the start of study treatment (Day 1) through up to the end of study (about 5 years).
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 - Immune response to AAV capsid proteins — From screening period through up to 5 years.
Changes in the expression levels of neutralizing and binding antibodies of AAV. - Immune response to FVIII transgene — From screening period through up to 5 years.
The changes of FVIII inhibitor and antibody levels - Viral vector shedding of GS001 — From date of infusion until the date of 3 consecutive documented negative results, assessed up to 1 year.
The vector shedding in serum, PMBC, saliva, urine, semen and feces will be monitored - Thrombosis risk assessment — From the start of study treatment (Day 1) through up to the end of study (about 5 years).
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.
Trial sites (1)
| Facility | City | Region | Status |
|---|---|---|---|
| Chinese Academy of Medical Science and Blood Disease Hospital | Tianjin | Tianjin Municipality | Recruiting |
More Institute of Hematology & Blood Diseases Hospital, China trials in China
Other trials for the same condition
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT04728841 on ClinicalTrials.gov ↗ ← All trials in China