Clinical trial NCT06125756: Safety and Efficacy Clinical Study of Severe Hemophilia B Treatment With KL001
Official title: Safety and Dose Finding Study of KL001 in Moderately Severe to Severe Hemophilia B Subjects
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Hemophilia B Without Inhibitor
Lead sponsor: Affiliated Hospital of Guangdong Medical University
Sponsor class: OTHER
First posted: 2023-11-09
Enrollment: 9
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment- related adverse events
timeFrame: Infusion to the completion of study, about 52 weeks
measure: Antibody against KL001 AAV vector capsid protein
timeFrame: Infusion to the completion of study, about 52 weeks
measure: Factor IX inhibitor
timeFrame: Infusion to the completion of study, about 52 weeks
Secondary outcomes:
measure: vector-derived FIX: C activity levels
timeFrame: From dosing day to week 52
measure: The annualized bleeding rate Before and After KL001 Infusion
timeFrame: From dosing day to week 52
measure: The annualized use of FIX
timeFrame: From dosing day to week 52
Other outcomes:
Locations:
Study officials:
affiliation: Affiliated Hospital of Guangdong Medical University
name: Liang Liang, MD
role: PRINCIPAL_INVESTIGATOR
References: