Gene Therapy for Chinese Hemophilia A
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexMale
Age18+
SponsorInstitute of Hematology & Blood Diseases Hospital, China
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Single group
Treatments tested in this trial
Injection of GS001
GeneticPatients 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 groups
12 Participants
are divided into 1 treatment groupGroup A: Treatment groupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of treatment- related adverse events
Number of patients experiencing treatment-related adverse events.
Time frame
From screening through up to the end of study (about 5 years).2
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.
Time frame
From the start of study treatment (Day 1) through up to the end of study (about 5 years).3
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.
Time frame
From the start of study treatment (Day 1) through up to the end of study (about 5 years).4
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
Time frame
From the start of study treatment (Day 1) through up to the end of study (about 5 years).Secondary outcomes
1
Vector- derived FVIII:C and FVIII antigen levels
Vector- derived FVIII:C and FVIII antigen levels will be measured after dosing.
Time frame
From pre-dose phase through up to 1 years post-dose2
FVIII usage within 1 year after GS001 infusion
Number of FVIII replacement therapies and total utilization of exogenous FVIII (IU/kg) replacement therapy.
Time frame
From week 3 to week 52 post GS001 infusion.3
Number of bleeding events requiring exogenous FVIII replacement therapy within 1 year after GS001 infusion
Number of bleeding events (Spontaneous and Traumatic) requiring exogenous FVIII replacement therapy
Time frame
Week 3 to Week 52 post GS001 Infusion4
Number of bleeding events within 1 year after GS001 infusion
Number of bleeding events (spontaneous or traumatic) including untreated bleeding events
Time frame
Week 3 to Week 52 post GS001 infusionOther outcomes
1
Long-term FVIII: C activity Level
FVIII: C activity Level at Year 2 (Week 104), Year 3 (Week 156), Year 4 (Week 208), Year 5 (Week 260) post GS001 Infusion
Time frame
From year 2 to year 5 post GS001 infusion.2
Annualized number of bleeding episodesrequiring exogenous FVIII replacement therapy during long-term follow up.
Annualized number of bleeding episodes requiring exogenous FVIII replacement therapy during every one-year period from Years 2 to Year 5 (week 53 to week 260) post GS001 infusion
Time frame
From year 2 to year 5 post GS001 infusion.3
Total utilization of FVIII replacement therapy (IU/kg) per year for long-term follow up.
Total utilization of FVIII replacement therapy (IU/kg) per year from Years 2 to Year 5 (week 53 to week 260) post GS001 infusion
Time frame
From year 2 to year 5 post GS001 infusion.4
Annualized number of bleeding episodes (spontaneous and traumatic) per year for long-term follow up.
Annualized number of bleeding episodes (spontaneous and traumatic) per year including untreated bleeding episodes per year from Years 2 to Year 5 (week 53 to week 260) post GS001 infusion.
Time frame
From year 2 to year 5 post GS001 infusion.Sponsors and contacts
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Source ClinicalTrials.gov