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)

Launched by CSL BEHRING · Aug 14, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new gene therapy called CSL222 (Etranacogene Dezaparvovec) for adults with Hemophilia B, a condition that affects blood clotting and can lead to excessive bleeding. The goal of the trial is to see how well this treatment works and if it is safe for people who have certain antibodies in their system that might affect the therapy's effectiveness. To participate, you need to have severe or moderately severe Hemophilia B and be on regular treatment with blood clotting factor. You also need to have had a significant number of previous treatments and detectable antibodies related to the gene therapy.

If you qualify for the study, you'll receive the CSL222 treatment and will be monitored closely to see how your body responds. Participants will need to keep a daily diary to track their health and any side effects. It's important to know that certain health conditions or previous treatments may prevent you from joining the trial, and you will need to agree to use contraception for a year after treatment. This study aims to improve the management of Hemophilia B and could help many patients in the future.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age ≥ 18 years and considered legally an adult, as defined by country regulations.
• • 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.
• Exclusion Criteria:
• • History of FIX inhibitors or positive FIX inhibitor test at Prescreening, Screening or Visit L Final (based on central laboratory results).
• • Screening or 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 ULN at Screening or Visit L-Final laboratory values (based on central laboratory results).
• • Any condition other than hemophilia B resulting in an increased bleeding tendency.
• • Thrombocytopenia, defined as a platelet count below 50 × 10\^9/L, at Screening or Visit L Final (based on central laboratory results).
• • Any uncontrolled or untreated infection (human immunodeficiency virus \[HIV\], hepatitis B virus \[HBV\] and hepatitis C virus \[HCV\], or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, cardiovascular, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease, alcoholism, drug dependency, or any other psychological disorder evaluated by the investigator to interfere with adherence to the clinical study protocol procedures or with the degree of tolerance to CSL222.
• • Known history of allergy to corticosteroids or known medical condition that would require chronic administration of oral corticosteroids.
• • Known uncontrolled allergic conditions or allergy / hypersensitivity to any component of the CSL222 excipients (ie, sucrose, potassium chloride, potassium dihydrogen phosphate, sodium chloride, and disodium hydrogen phosphate).
• • Previous gene therapy treatment.
• • Receipt of an experimental agent or device within 60 days before Screening until the end of the study.