Hemophilia B Without Inhibitor
Conditions
Brief summary
This is an open- label, non- randomized, uncontrolled, dose-escalation pilot study to evaluate the safety and efficacy of KL001 injection solution in hemophilia B subjects with ≤2 IU/dl residual FIX levels.
Detailed description
This is an open- label, non- randomized, uncontrolled, dose-escalation pilot study to evaluate the safety and efficacy of KL001 injection solution in hemophilia B subjects with ≤2 IU/dl residual FIX levels. Nine subjects will be enrolled and administered with three different doses of KL001. Subjects will provide informed consent and then undergo screening assessments up to 1 month prior administration of KL001. All subjects will undergo 52 weeks safety observation and will be encouraged to enroll in an extension study to evaluate long- term safety of KL001 for total 5 years.
Interventions
DRUGLow dose KL001
Subjects will be dosed with single dose of KL001 at 2.5x10\^12 vg/kg.
Subjects will be dosed with single dose of KL001 at 5.0x10\^12 vg/kg.
DRUGHigh dose KL001
Subjects will be dosed with single dose of KL001 at 1.0x10\^13 vg/kg.
Sponsors
Affiliated Hospital of Guangdong Medical University
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Low dose group will be administrated with 2.5×10\^12 vg/kg; Middle dose group will be administrated with 5.0×10\^12 vg/kg; High dose group will be administrated with 1.0×10\^13 vg/kg.
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male ≥12 years of age. 2. Moderate/severe or severe hemophilia B (baseline FIX activity ≤2% of normal or documented history of FIX activity ≤2%). 3. At least 3 bleeding episodes per year that require on-demand treatment with FIX or are treated with a prophylactic regimen of FIX. 4. At least 100 days exposure history to recombinant or plasma-derived FIX protein products. 5. No neutralizing antibodies to exogenous FIX protein products. 6. Willing and able to comply with study procedures and requirements.
Exclusion criteria
1. Suffering from chronic inflammatory muscle disease. 2. Positive in Hepatitis B or Hepatitis C. 3. Infection with HIV-1 or HIV-2 and CD4+T cell count ≤ 200/ μ L. 4. History of thrombosis or susceptibility to thrombosis. 5. Current or previous participation in another gene therapy study. 6. Has any other significant medical condition that the investigator feels would be a risk to the subject or would impede the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment- related adverse events | Infusion to the completion of study, about 52 weeks | Number and severity of adverse events and serious adverse events and relationship to KL001 |
| Antibody against KL001 AAV vector capsid protein | Infusion to the completion of study, about 52 weeks | Immune response against AAV capsid will be evaluated by measurement of the total antibody and neutralizing antibody against AAV capsid protein in plasma samples collected at multiple timepoints after dosing up to 52 weeks |
| Factor IX inhibitor | Infusion to the completion of study, about 52 weeks | Development of inhibitor against vector-derived Factor IX protein will be measured using bethesda method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| vector-derived FIX: C activity levels | From dosing day to week 52 | Peak and steady-state activity levels of vector-derived FIX: C |
| The annualized bleeding rate Before and After KL001 Infusion | From dosing day to week 52 | The annualized bleeding rate (ABR) will be calculated for all subjects through Week 52 |
| The annualized use of FIX | From dosing day to week 52 | The use of on-demand FIX replacement therapy was recorded by dose (IU/kg) administered, and the annualized use of FIX replacement therapy was calculated for all subjects through Week 52. |
Contacts
Primary ContactLiang Liang, MD
Outcome results
None listed