Etranacogene dezaparvovec for Hemophilia B (severe or moderately severe)

Inclusion criteria

• {"criterion_text":"- 1) Age ≥ 18 years and considered legally an adult, as defined by country regulations."}
• {"criterion_text":"- 2) Has congenital hemophilia B with known severe or moderately severe FIX deficiency (less than or equal to [≤] 2% of normal circulating FIX) for which the subject is on continuous routine FIX prophylaxis."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 4) Has greater than (>) 150 previous exposure days to FIX replacement therapy"}
• {"criterion_text":"- 5) Has been on stable FIX prophylaxis for at least 2 months before Screening."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 7) Acceptance to adhere to contraception"}
• {"criterion_text":"- 8) Able to provide informed consent after receipt of verbal and written information about the study."}
• {"criterion_text":"- 9) 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

• {"criterion_text":"- 1) History of FIX inhibitors or positive FIX inhibitor test at Prescreening, Screening or Visit L-Final (based on central laboratory results)."}
• {"criterion_text":"- 10) Receipt of an experimental agent or device within 60 days before Screening until the end of the study."}
• {"criterion_text":"- 2) Screening or Visit L-Final laboratory values (based on central laboratory results) of total bilirubin > 2 × the upper limit of normal (ULN) (except if caused by Gilbert’s syndrome)."}
• {"criterion_text":"- 3) Screening or Visit L-Final laboratory values (based on central laboratory results).of any of the following laboratory abnormalities: •\tAlanine aminotransferase (ALT) > 2 × the ULN •\tAspartate aminotransferase (AST) > 2 × the ULN •\tAlkaline phosphatase > 2 × the ULN •\tSerum creatinine > 2 × the ULN •\tHemoglobin < 8 g/dL"}
• {"criterion_text":"- 4) Any condition other than hemophilia B resulting in an increased bleeding tendency."}
• {"criterion_text":"- 5) Thrombocytopenia, defined as a platelet count 50 × 10^9/L, at Screening or Visit L-Final (based on central laboratory results)."}
• {"criterion_text":"- 6) 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."}
• {"criterion_text":"- 7) Known history of allergy to corticosteroids or known medical condition that would require chronic administration of oral corticosteroids."}
• {"criterion_text":"- 8) 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)."}
• {"criterion_text":"- 9) Previous gene therapy treatment."}

Primary endpoints

• {"endpoint_text":"- Annualized bleeding rate (ABR)","definition_or_measurement_approach":"ABR measured as the annualized rate of bleeding events; primary objective frames assessment during the 52 weeks following CSL222 treatment after establishment of stable FIX expression (Months 7 to 18 postdose) compared to standard of care continuous routine FIX prophylaxis during the ≥ 6-month Lead-in Period."}

Secondary endpoints

• {"endpoint_text":"- 1) Number of participants with Treatment Emergent Adverse Events (TEAEs).","definition_or_measurement_approach":"Count of participants experiencing TEAEs."}
• {"endpoint_text":"- 2) Percentage of participants with TEAEs.","definition_or_measurement_approach":"Proportion (%) of participants with TEAEs."}
• {"endpoint_text":"- 3) Number of TEAEs.","definition_or_measurement_approach":"Total count of TEAE events."}
• {"endpoint_text":"- 4) Change in Liver ultrasound.","definition_or_measurement_approach":"Change in liver ultrasound findings over time (imaging assessment)."}
• {"endpoint_text":"- 5) Number of participants who develop Factor IX (FIX) Inhibitors.","definition_or_measurement_approach":"Count of participants with new FIX inhibitors."}
• {"endpoint_text":"- 6) Percentage of participants who develop Factor IX (FIX) Inhibitors.","definition_or_measurement_approach":"Proportion (%) of participants developing FIX inhibitors."}
• {"endpoint_text":"- 7) Change in hematology and biochemistry parameters.","definition_or_measurement_approach":"Change from baseline in laboratory hematology and biochemistry parameters."}
• {"endpoint_text":"- 8) Number of participants with clinically significant increase in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST).","definition_or_measurement_approach":"Count of participants with clinically significant ALT or AST increases."}
• {"endpoint_text":"- 9) Percentage of participants with clinically significant increase in ALT or AST.","definition_or_measurement_approach":"Proportion (%) of participants with clinically significant ALT/AST increases."}
• {"endpoint_text":"- 10) Corticosteroid use for ALT or AST increases after CSL222 treatment.","definition_or_measurement_approach":"Number or proportion of participants requiring corticosteroid use for transaminase increases post-treatment."}
• {"endpoint_text":"- 11) Number of participants with clinically significant Alpha-fetoprotein (AFP).","definition_or_measurement_approach":"Count of participants with clinically significant AFP elevations."}
• {"endpoint_text":"- 12) Percentage of participants with clinically significant AFP.","definition_or_measurement_approach":"Proportion (%) of participants with clinically significant AFP."}
• {"endpoint_text":"- 13) Number of participants with infusion related reactions or hypersensitivity reactions.","definition_or_measurement_approach":"Count of participants with infusion-related or hypersensitivity reactions."}
• {"endpoint_text":"- 14) Percentage of participants with infusion related reactions or hypersensitivity reactions.","definition_or_measurement_approach":"Proportion (%) of participants with infusion-related or hypersensitivity reactions."}
• {"endpoint_text":"- 15) Change in the Uncontaminated Endogenous FIX activity.","definition_or_measurement_approach":"Change from baseline in uncontaminated endogenous FIX activity."}
• {"endpoint_text":"- 16) Annualized consumption of FIX replacement therapy.","definition_or_measurement_approach":"Annualized amount of FIX replacement therapy consumed."}
• {"endpoint_text":"- 17) Annualized infusion rate of FIX replacement therapy.","definition_or_measurement_approach":"Annualized number/rate of FIX infusions."}
• {"endpoint_text":"- 18) Number of participants remaining free of continuous routine FIX prophylaxis.","definition_or_measurement_approach":"Count of participants who discontinue continuous routine FIX prophylaxis."}
• {"endpoint_text":"- 19) Percentage of participants remaining free of continuous FIX prophylaxis.","definition_or_measurement_approach":"Proportion (%) of participants free of continuous routine FIX prophylaxis."}
• {"endpoint_text":"- 20) ABR for spontaneous bleeding episodes.","definition_or_measurement_approach":"Annualized bleeding rate specifically for spontaneous bleeds."}
• {"endpoint_text":"- 21) ABR for joint bleeding episodes.","definition_or_measurement_approach":"Annualized bleeding rate for joint bleeds."}
• {"endpoint_text":"- 22) ABR for FIX-treated bleeding episodes.","definition_or_measurement_approach":"Annualized bleeding rate for bleeds treated with FIX."}
• {"endpoint_text":"- 23) Correlation analysis of FIX activity levels with baseline AAV5 NAb titers.","definition_or_measurement_approach":"Correlation analysis between measured FIX activity levels and baseline AAV5 neutralizing antibody titers."}
• {"endpoint_text":"- 24) Number of participants with new target joints and resolved preexisting target joints.","definition_or_measurement_approach":"Count of participants developing new target joints or with resolution of preexisting target joints."}
• {"endpoint_text":"- 25) Number of participants with zero bleeding episodes and zero FIX-treated bleeding episodes .","definition_or_measurement_approach":"Count of participants with zero total bleeding episodes and zero FIX-treated bleeding episodes."}
• {"endpoint_text":"- 26) Percentage of participants with zero bleeding episodes and zero FIX-treated bleeding episodes","definition_or_measurement_approach":"Proportion (%) of participants with zero total and zero FIX-treated bleeds."}
• {"endpoint_text":"- 27) Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score.","definition_or_measurement_approach":"Change from baseline in EQ-5D-5L VAS overall score."}
• {"endpoint_text":"- 28) Change in the EQ-5D-5L Index Scores.","definition_or_measurement_approach":"Change from baseline in EQ-5D-5L index scores."}
• {"endpoint_text":"- 29) Number of paticipant with Uncontaminated Endogenous FIX Activity of greater than or equal to >=5%","definition_or_measurement_approach":"Count of participants achieving uncontaminated endogenous FIX activity ≥ 5%."}
• {"endpoint_text":"- 30) Percentage of participant with Uncontaminated Endogenous FIX Activity of >=5%","definition_or_measurement_approach":"Proportion (%) of participants with uncontaminated endogenous FIX activity ≥ 5%."}

Poland

Earliest CTIS Part Ii Submission Date

13-01-2025

Latest Decision Or Authorization Date

29-08-2025

Processing Time Days

228

Number Of Sites

1

Number Of Participants

2

Bulgaria

Earliest CTIS Part Ii Submission Date

10-01-2025

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

370

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

CSL Behring LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

Multiple sponsor duties including site payments and other operational tasks (sponsorDuties codes 1,12,13,15,4,5,8).

Name

PAREXEL International GmbH

Responsibilities

Sponsor duties code 10.

Name

Fortrea Inc.

Responsibilities

Sponsor duties include code 6 and code 15 (SAE reconciliation).

Name

Suvoda LLC

Responsibilities

Sponsor duties code 3.

Name

Medidata Solutions Inc.

Responsibilities

Sponsor duties code 7.

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties: code 6; contact Nadine.tavares@fortrea.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"sponsorDuties: code 15: Long term sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"sponsorDuties: codes 1,12,13,15 (Site payments),4,5,8; contact RS-Advisor-Support@medpace.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Preventiongenetics LLC","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties: code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"sponsorDuties: code 15: Long term sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"ProtaGene CGT GmbH","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Unilabs A/S","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties: code 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"PAREXEL International GmbH","duties_or_roles":"sponsorDuties: code 10","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Block Clinical Inc.","duties_or_roles":"sponsorDuties: code 15: Patient Travel","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties: code 15: SAE reconciliation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties: code 7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}