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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophilia B Without Inhibitor
• Intervention / Treatment: Drug: Low dose KL001; Drug: Middle dose KL001; Drug: High dose KL001

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 Type: Interventional
• Enrollment (Estimated): 9
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Liang Liang, MD; Phone Number: +86 13560539300; Email: 13560539300@139.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KL001 injection solution; Subjects will be dosed with three different dose of KL001 injection solution at 2.5x10^12 vg/kg to 1.0x10^13 vg/kg.	Drug: Low dose KL001; Subjects will be dosed with single dose of KL001 at 2.5x10^12 vg/kg.; Other Names: rAAV vector; Drug: Middle dose KL001; Subjects will be dosed with single dose of KL001 at 5.0x10^12 vg/kg.; Other Names: rAAV vector; Drug: High dose KL001; Subjects will be dosed with single dose of KL001 at 1.0x10^13 vg/kg.; Other Names: rAAV vector

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
vector-derived FIX: C activity levels	Peak and steady-state activity levels of vector-derived FIX: C	From dosing day to week 52
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
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

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Guangdong Medical University
• Investigators: Principal Investigator: Liang Liang, MD, Affiliated Hospital of Guangdong Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 20, 2023
• Primary Completion (Estimated): September 20, 2024
• Study Completion (Estimated): October 30, 2025

Study Registration Dates

• First Submitted: October 31, 2023
• First Submitted That Met QC Criteria: November 5, 2023
• First Posted (Estimated): November 9, 2023

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 5, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: CP-KL001-001/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No