None listed
Conditions
Interventions
Genetic : Substance name : CSL222, Trade name : HEMGENIX, Dose : 2 × 10^13 gc/kg, one-time infusion in a peripheral vein
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years. 2. Has congenital hemophilia B with known severe or moderately severe FIX deficiency (= 2% of normal circulating FIX) for which the subject is on continuous routine FIX prophylaxis. Note: Continuous routine FIX prophylaxis is defined as the intent of treating with an a priori defined frequency of infusions (eg, twice weekly, once every 2 weeks, etc.) as documented in the medical records. 3. 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). Note: Subjects who do not have detectable AAV5 NAb titer at Prescreening or Screening can be rescreened once. Study Number: CSL222_3005 Study Product: CSL222 (etranacogene dezaparvovec) Protocol version: Amendment 1 Page 45 of 95 Protocol date: 12 April 2023 Confidential RnD-FORM-000203241 Version 4.0 4. Has > 150 previous exposure days to FIX replacement therapy. 5. Has been on stable FIX prophylaxis for at least 2 months before Screening. 6. Has demonstrated capability to independently, accurately, and in a timely manner complete the eDiary during the Lead-in Period, as judged by the investigator. 7. Acceptance to barrier contraception protection for 1 year starting the day of CSL222 treatment. 8. Able to provide informed consent after receipt of verbal and written information about the study. 9. Investigator believes that the subject (or the subject’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
Exclusion criteria: 1. History of FIX inhibitors or positive FIX inhibitor test at Screening or Visit L-Final (based on central laboratory results). 2. 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): - Food and Drug Administration (FDA) or European Medicines Agency (EMA) Child Pugh Grade C (10 to 15 points) or - Total bilirubin > 3 × the upper limit of normal (ULN) and elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > the ULN. 3. ALT > 2 × the ULN at Screening and Visit L-Final laboratory values (based on central laboratory results) 4. Any condition other than hemophilia B resulting in an increased bleeding tendency. 5. Thrombocytopenia, defined as a platelet count below 50 × 109/L, at Screening and Visit L-Final (based on central laboratory results). 6. Any uncontrolled or untreated infection (human immunodeficiency virus [HIV], hepatitis C, etc) 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. 7. Known significant medical condition that may significantly impact the intended transduction of the vector and / or expression and activity of the protein, including but not limited to: a. Disseminated intravascular coagulation. b. Accelerated fibrinolysis. c. Advanced liver fibrosis (suggestive of or equal to Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] Stage 3 disease, eg, a FibroScan™ score of = 9 kPa is considered equivalent, or alternatively shear wave elastography or magnetic resonance imaging elastography). 8. Known history of allergy to corticosteroids or known medical condition that would require chronic administration of steroids. 9. Known uncontrolled allergic conditions or allergy / hypersensitivity to any component of the CSL222 excipients. 10. Previous gene therapy treatment. 11. Receipt of an experimental agent or device within 60 days before Screening until the end of the study. 12. Received any vaccination(s) 30 days prior to CSL222 treatment or have a vaccination planned within 16 weeks after CSL222 treatment. 13. Alcohol, drug, or medication abuse within 1 year before providing informed consent. 14. Currently receiving a therapy not permitted during the study, as defined in Section 6.8.3. 15. Pregnant or breastfeeding. 16. Involved in the planning and / or conduct of the study (applies to CSL Behring [CSLB] staff, staff at the study site, and third-party vendors).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Descriptive statistics of ABR(annualized bleeding rate) in the Lead-in Period and during the 52 weeks following stable FIX expression (Months 7 to 18 postdose). | — |
Secondary
| Measure | Time frame |
|---|---|
| TEAE (treatment-emergent adverse event), TESAE (treatment-emergent serious adverse event), and TEAESI (treatment-emergent adverse event of special interest);Abdominal ultrasound;FIX inhibitors;Hematology and serum chemistry parameters;ALT (alanine aminotransferase) / AST (aspartate aminotransferase) levels;Corticosteroid treatment for ALT (alanine aminotransferase) / AST (aspartate aminotransferase) increases;AFP (alpha-fetoprotein);Infusion Related Reactions / Hypersensitivity Reactions;Endogenous FIX activity and change from baseline;Annualized consumption of FIX replacement therapy;Annualized infusion rate of FIX replacement therapy;Subjects remaining free of previous continuous routine FIX prophylaxis;ABR (annualized bleeding rate) for spontaneous bleeding episodes, ABR (annualized bleeding rate) for joint bleeding episodes, and ABR (annualized bleeding rate) for FIX-treated bleeding episodes;Paired data of FIX activity levels and baseline AAV5 (adeno-associated virus serotype 5) Nab (neutralizing antibody) titers; Occurrence (and resolution) of new target joints ;Subjects with zero bleeds;EQ-5D-5L (EuroQol-5 dimensions-5 levels) VAS (Visual Analogue Scale) and Index scores and the change from baseline | — |
Countries
Korea, Republic of
Contacts
Public ContactHyojung Jung
Yonsei University Health System, Severance Hospital
Outcome results
None listed