Efficacy and Safety of CSL222 (Etranacogene Dezaparvovec) Gene Therapy in Adults With Hemophilia B With Pretreatment Adeno-associated Virus Serotype 5 (AAV5) Neutralizing Antibodies (Nabs)
- Conditions
- Hemophilia B
- Interventions
- Genetic: CSL222 (AAV5-hFIXco-Padua)
- Registration Number
- NCT06003387
- Lead Sponsor
- CSL Behring
- Brief Summary
The purpose of this study is to assess the risk of bleeding due to failure of expected pharmacological action of CSL222 in adults with severe or moderately severe hemophilia B with detectable pretreatment AAV5 Nabs.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 35
- Has congenital hemophilia B with known severe or moderately severe FIX deficiency (≤ 2% of normal circulating FIX) for which the participant is on continuous routine FIX prophylaxis
- Has 2 consecutive detectable AAV5 NAb titer results between Screening and Visit L-Final using a validated AAV5 NAb assay (based on central laboratory results)
- Has > 150 previous exposure days to FIX replacement therapy
- Has been on stable FIX prophylaxis for at least 2 months before Screening
- Has demonstrated capability to independently, accurately, and in a timely manner complete the eDiary during the Lead-in Period, as judged by the investigator
- Acceptance to barrier contraception protection for 1 year starting the day of CSL222 treatment
- Able to provide informed consent after receipt of verbal and written information about the study
- Investigator believes that the participant (or the participant's legally acceptable representative[s]) understands the nature, scope, and possible consequences of the study and is able to adhere to the study procedures.
- History of FIX inhibitors or positive FIX inhibitor test at Screening or Visit L (lead-in period)-Final (based on central laboratory results)
- Screening and Visit L-Final laboratory values that meet the definition of Severe Hepatic Impairment per Common Terminology Criteria for Adverse Events (CTCAE) (based on central laboratory results)
- ALT > 2 × the upper limit of normal (ULN) at Screening and Visit L-Final (based on central laboratory results)
- Any condition other than hemophilia B resulting in an increased bleeding tendency
- Any uncontrolled or untreated infection (human immunodeficiency virus [HIV], hepatitis C, etc.) or any other significant concurrent, uncontrolled medical condition evaluated by the investigator to interfere with adherence to the clinical study protocol or with the degree of tolerance to CSL222.
- Thrombocytopenia, defined as a platelet count below 50 × 10^9/L, at Screening and Visit L-Final (based on central laboratory results)
- Known history of allergy to corticosteroids or known medical condition that would require chronic administration of steroids.
- Known uncontrolled allergic conditions or allergy / hypersensitivity to any component of the CSL222 excipients
- Previous gene therapy treatment
- Receipt of an experimental agent or device within 60 days before Screening until the end of the study.
- Note: Other protocol pre-specified exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CSL222 CSL222 (AAV5-hFIXco-Padua) Participants will receive CSL222 as a single intravenous (IV) infusion of 2 × 10\^13 genome copies per kilogram (gc/kg) on Day D.
- Primary Outcome Measures
Name Time Method Annualized Bleeding Rate (ABR) Post-dose: Months 7 to 18 The total, spontaneous, joint, and Factor IX (FIX)-treated bleeding episodes will be analyzed. ABR is calculated as the total bleeding episodes divided by the total time at risk.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Treated With Corticosteroids For Change in ALT or AST Up to 18 months post dose Percentage of Participants With TEAEs, TESAEs, and TEAESIs Post-dose: At Months 6,12, and 18 Number of TEAEs, TESAEs, and TEAESIs Post-dose: At Months 6,12, and 18 Percentage of Participants who Develop FIX Inhibitors Up to 18 months post dose Number of Participants with Clinically Significant Hematology and Serum Chemistry Parameters Up to 18 months post dose Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs), and TEAEs of Special Interest (TEAESIs) Post-dose: At Months 6,12, and 18 Number of Participants with Clinically Significant Change in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Up to 18 months post dose Percentage of Participants With Infusion Related Reactions or Hypersensitivity Reactions Up to 18 months post dose Change From Baseline in the Endogenous FIX Activity Baseline up to Months 6, 12, and 18 post dose Number of Participants with Change From Baseline in Abdominal Ultrasound Baseline up to 18 months post dose Number of Participants Who Develop Factor IX (FIX) Inhibitors Up to 18 months post dose Percentage of Participants With Clinically Significant Hematology and Serum Chemistry Parameters Up to 18 months post dose Percentage of Participants With Clinically Significant Change in ALT or AST Up to 18 months post dose Number of Participants Treated With Corticosteroids For Change in ALT or AST Up to 18 months post dose Number of Participants With Clinically Significant Alpha-fetoprotein (AFP) Up to 18 months post dose Number of Participants with Infusion Related Reactions or Hypersensitivity Reactions Up to 18 months post dose Annualized Infusion Rate of FIX Replacement Therapy Post-dose: Months 7 to 18 ABR for Spontaneous Bleeding Episodes, Joint Bleeding Episodes, and FIX-treated Bleeding Episodes Separately Post-dose: Months 7 to 18 Percentage of Participants With Clinically Significant AFP Up to 18 months post dose Number of Participants With the Endogenous FIX Activity Post-dose: At Months 6, 12, and 18 Annualized Consumption of FIX Replacement Therapy Post-dose: Months 7 to 18 Hemophilia Quality of Life Questionnaire (Hem-A-QoL) Total Score and Treatment Domain Score Post-dose: Months 6 to 18 The Hem-A-QoL (Hemophilia Quality of Life Questionnaire for Adults) consists of 46 items comprising 10 domains: physical health, feelings, treatment, work and school, dealing with hemophilia, family planning, future, partnerships and sexuality, sports and leisure, and view of yourself for which responses will be recorded from 5 options (never, seldom, sometimes, often, and always; for some items, there is also a "not applicable" option). The Hem-A-QoL Total Score and Treatment Domain Score range from 0 to 100, with lower scores reflecting a better quality of life.
Change From Baseline in the Hem-A-QoL Total Score and Treatment Domain Score Baseline, Months 6 to 18 post dose The Hem-A-QoL consists of 46 items comprising 10 domains: physical health, feelings, treatment, work and school, dealing with hemophilia, family planning, future, partnerships and sexuality, sports and leisure, and view of yourself for which responses will be recorded from 5 options (never, seldom, sometimes, often, and always; for some items, there is also a "not applicable" option). The Hem-A-QoL Total Score and Treatment Domain Score range from 0 to 100, with lower scores reflecting a better quality of life. The change from baseline in the Hem-A-QoL Total Score and Treatment Domain Score will be determined.
Percentage of Participants Remaining Free of Previous Continuous Routine FIX Prophylaxis Post-dose: Months 7 to 18 Number of Participants With New Target Joints and Resolved New or Preexisting Target Joints Post-dose: Months 7 to 18 Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint.
Correlation Analysis of FIX Activity Levels Post-dose: Months 6 to 18 Number of Participants With Zero Bleeds Following Stable FIX Expression Post-dose: Months 7 to 18 EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score Post-dose: Months 6 to 18 The EQ-5D-5L questionnaire visual analogue scale (VAS) measures overall health status on a vertical VAS ranging from 0 to 100. A higher score indicates better quality of life.
Percentage of Participants With Zero Bleeds Following Stable FIX Expression Post-dose: Months 7 to 18 EQ-5D-5L Index Scores Post-dose: Months 6 to 18 The EQ-5D-5L questionnaire descriptive system of health-related quality of life consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) for which responses will be recorded on 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and extreme problems). The responses will be converted into a single index utility score (typically between -0.6 and 1). A higher score indicates better quality of life.
Change from Baseline in the EQ-5D-5L VAS Score Baseline, Months 6 to 18 post dose The EQ-5D-5L questionnaire visual analogue scale (VAS) measures overall health status on a vertical VAS ranging from 0 to 100. A higher score indicates better quality of life. The change from baseline in the EQ-5D-5L VAS score will be determined.
Change From Baseline in the EQ-5D-5L Index Scores Baseline, Months 6 to 18 post dose The EQ-5D-5L questionnaire descriptive system of health-related quality of life consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) for which responses will be recorded on 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and extreme problems). The responses will be converted into a single index utility score (typically between -0.6 and 1). A higher score indicates better quality of life. The change from baseline in the EQ-5D-5L index score will be determined.
Trial Locations
- Locations (11)
Royal Brisbane Hospital - 03600045
🇦🇺Herston, Queensland, Australia
Royal Prince Alfred Hospital - 03600044
🇦🇺Camperdown, New South Wales, Australia
University of Michigan - 84000285
🇺🇸Ann Arbor, Michigan, United States
The Alfred Hospital - 03600043
🇦🇺Melbourne, Victoria, Australia
McMaster University - Hamilton - 12400017
🇨🇦Hamilton, Ontario, Canada
Sheba Medical Center - 37600004
🇮🇱Tel Hashomer, Israel
Kyungpook National University Hospital - 41000014
🇰🇷Daegu, Korea, Republic of
Kyung Hee University Hospital at Gangdong - 41000015
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System - 41000013
🇰🇷Seoul, Korea, Republic of
King Faisal Specialist Hospital and Research Center - 68200001
🇸🇦Riyadh, Saudi Arabia
Haemophilia Comprehensive Care Centre - 71000001
🇿🇦Johannesburg, South Africa