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)

CSL Behring

Status and phase

Enrolling

Phase 3

Conditions

Hemophilia B

Treatments

Genetic: CSL222 (AAV5-hFIXco-Padua)

Study type

Interventional

Funder types

Industry

Identifiers

NCT06003387

2023-509590-23-00 (EU Trial (CTIS) Number)

CSL222_3005

Details and patient eligibility

About

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.

Enrollment

35 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.