Severe Hemophilia A
Conditions
Brief summary
This study is a single-arm, open-label study evaluating the safety and efficacy of GS1191-0445 injection as a single dose in Chinese subjects with severe hemophilia A. GS1191-0445 is an adeno-associated virus 8 (AAV8)-delivered gene therapy designed to express B-domain deleted human factor VIII (FVIII) under the regulation of a human liver-specific promoter. Following a single intravenous administration, AAV8 gene expression cassette, which transfects hepatocytes and facilitates the specific expression and secretion of FVIII into the blood.
Interventions
A single intravenous administration of GS1191-0445 injection at a dose of 3E12 vg/kg
Sponsors
Gritgen Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Understand the purpose and risks of the study and provide informed consent in accordance with national and local privacy laws: 2. Subject must be male, aged ≥18 years old at the time of signing informed consent: 3. Participants with confirmed severe hemophilia A in their pre-admission history and based on clinical laboratory examination; 4. Subjects had used FVIII products for at least 150 exposure days (ED) before enrollment; 5. Subject has received continuous prophylactic treatment with exogenous FVIII for one year prior to enrollment or has been treated with exogenous FVIII on demand; 6. Subject has no history of hypersensitivity or allergic reactions related to the administration of FVIII agents; 7. Subject has no history of FVIII inhibitors. 8. Subjects agree to use a reliable barrier contraceptive method from the date of signing the informed consent 9. Subject is willing and able to follow planned visits, treatment plans, and other study procedures.
Exclusion criteria
1. The subject has any hemorrhagic disorder not related to hemophilia A, 2. Abnormal liver function test results of subjects during screening. 3. Abnormal laboratory examination of subjects during screening 4. The subject has acute or chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection; Or are receiving antiviral treatment for hepatitis B and C; 5. Active systemic immune disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with Adverse Events (AE) as assessed by CTCAE v5.0, including Adverse Event of Special Interests (AESI) and Serious Adverse Events (SAE); | Five years after infusion |
| Number of Participants with Thrombosis Risk: In subjects with >150% FⅧ:C post-GS1191-0445 infusion, VTE risk will be assessed via Caprini model, coagulation function, D-dimer, FDP, and TAT; | Five years after infusion |
| The shedding of GS1191-0445 viral vector: Viral vector titers in serum, saliva, urine, semen and fecal will be monitored; | Five years after infusion |
| Total FⅧ Antibody Levels: Total FⅧ antibody levels will be measured to determine the immunogenicity of FⅧ expression protein; | Five years after infusion |
| FVIII inhibitor: Factor Ⅷ inhibitor will be measured to determine the immunogenicity of FⅧ expression protein; | Five years after infusion |
| The number of dose-limiting toxicity (DLT) events will be determined by the Safety Review Committee (SRC), at least 12 weeks after GS1191-0445 infusion. | Five years after infusion |
| The Change of Laboratory Values: Change in serum chemistry values including liver function tests, hematology, and urinalysis; | Five years after infusion |
| Changes for vital signs: Includes sitting blood pressure (mmHg), respiratory rate (breaths/min), body temperature (°C), and pulse rate (beats/min); | Five years after infusion |
| Changes for physical examination: Includes skin, mucous membranes, lymph nodes, head and neck, chest (heart, lungs), abdomen, muscles, nervous system, spine/extremities; | Five years after infusion |
| The immunogenicity of AAV capsid protein: Collection of Peripheral Blood Mononuclear Cell (PBMC) and serum samples for vector shedding detection; | Five years after infusion |
Secondary
| Measure | Time frame |
|---|---|
| Vector-derived FⅧ Activity Level: Validated methods will be used to measure vector-derived FⅧ activity, including peak and steady state following GS1191-0445 infusion； | Day 4 to Week 52 after infusion |
| Total Consumption of Exogenous FⅧ Infusion; | Weeks 3 to 52 and five years after infusion |
| Annualized Consumption of FⅧ Infusion； | Weeks 3 to 52 and five years after infusion |
| Number of bleeding events requiring exogenous FⅧ infusion: To assess the number of bleeding events requiring exogenous FⅧ infusion after administration; | Weeks 3 to 52 and five years after infusion |
| Number of bleeding events: To assess bleeding events, including spontaneous, traumatic and untreated bleeding events after administration | Weeks 3 to 52 and five years after infusion |
| Number of joint bleeding events: To assess joint bleeding events after administration | Weeks 3 to 52 and five years after infusion |
Countries
China
Outcome results
None listed