Safety and Efficacy Clinical Study of Severe Hemophilia B Treatment With KL001

Early Phase 1

Not yet recruiting

• Conditions: Hemophilia B Without Inhibitor
• Interventions: Drug: Low dose KL001; Drug: Middle dose KL001; Drug: High dose KL001

• Registration Number: NCT06125756
• Lead Sponsor: Affiliated Hospital of Guangdong Medical University

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.

Study Timeline

• Study First Submitted: 2023-10-31
• Status Verified: 2023-11
• Study First Submitted QC: 2023-11-05
• Last Update Submitted: 2023-11-05
• Study First Posted: 2023-11-09
• Last Update Posted: 2023-11-09
• Study Start: 2023-12-20
• Primary Completion: 2024-09-20
• Study Completion: 2025-10-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
KL001 injection solution	Low dose KL001	Subjects will be dosed with three different dose of KL001 injection solution at 2.5x10\^12 vg/kg to 1.0x10\^13 vg/kg.
KL001 injection solution	Middle dose KL001	Subjects will be dosed with three different dose of KL001 injection solution at 2.5x10\^12 vg/kg to 1.0x10\^13 vg/kg.
KL001 injection solution	High dose KL001	Subjects will be dosed with three different dose of KL001 injection solution at 2.5x10\^12 vg/kg to 1.0x10\^13 vg/kg.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.