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

Hemophilia B Without Inhibitor Clinical Trial

Official title:

Safety and Dose Finding Study of KL001 in Moderately Severe to Severe Hemophilia B Subjects

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06125756
• Other study ID #: CP-KL001-001/01
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: December 20, 2023
• Est. completion date: October 30, 2025

Study information

• Verified date: November 2023
• Source: Affiliated Hospital of Guangdong Medical University
• Contact: Liang Liang, MD
• Phone: +86 13560539300
• Email: 13560539300[@]139.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 9
• Est. completion date: October 30, 2025
• Est. primary completion date: September 20, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B
• Hemophilia B Without Inhibitor

Intervention

Drug:
• Low dose KL001
Subjects will be dosed with single dose of KL001 at 2.5x10^12 vg/kg.
• Middle dose KL001
Subjects will be dosed with single dose of KL001 at 5.0x10^12 vg/kg.
• High dose KL001
Subjects will be dosed with single dose of KL001 at 1.0x10^13 vg/kg.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Hospital of Guangdong Medical University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment- related adverse events	Number and severity of adverse events and serious adverse events and relationship to KL001	Infusion to the completion of study, about 52 weeks
Primary	Antibody against KL001 AAV vector capsid protein	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	Infusion to the completion of study, about 52 weeks
Primary	Factor IX inhibitor	Development of inhibitor against vector-derived Factor IX protein will be measured using bethesda method.	Infusion to the completion of study, about 52 weeks
Secondary	vector-derived FIX: C activity levels	Peak and steady-state activity levels of vector-derived FIX: C	From dosing day to week 52
Secondary	The annualized bleeding rate Before and After KL001 Infusion	The annualized bleeding rate (ABR) will be calculated for all subjects through Week 52	From dosing day to week 52
Secondary	The annualized use of FIX	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.	From dosing day to week 52