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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06003387
Registration number
NCT06003387
Ethics application status
Date submitted
1/08/2023
Date registered
22/08/2023
Date last updated
15/07/2025
Titles & IDs
Public title
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)
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Scientific title
Phase 3b, Open-label, Multicenter, Single-dose Study Investigating Efficacy and Safety of CSL222 (Etranacogene Dezaparvovec) Gene Therapy Administered to Adult Subjects With Severe or Moderately Severe Hemophilia B With Detectable Pretreatment AAV5 Neutralizing Antibodies
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Secondary ID [1]
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2023-509590-23-00
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Secondary ID [2]
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CSL222_3005
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Hemophilia B
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Condition category
Condition code
Blood
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Clotting disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Other - CSL222 (AAV5-hFIXco-Padua)
Experimental: CSL222 - Participants will receive CSL222 as a single intravenous (IV) infusion of 2 × 10\^13 genome copies per kilogram (gc/kg) on Day 1.
Treatment: Other: CSL222 (AAV5-hFIXco-Padua)
Administered as a single IV infusion.
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Intervention code [1]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Annualized Bleeding Rate (ABR)
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Assessment method [1]
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The total bleeding episodes will be analyzed. ABR is calculated as the total bleeding episodes divided by the total time at risk.
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Timepoint [1]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [1]
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Number of participants with Treatment Emergent Adverse Events (TEAEs)
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Assessment method [1]
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Timepoint [1]
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Up to 60 months after CSL222 treatment
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Secondary outcome [2]
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Percentage of participants with TEAEs
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Assessment method [2]
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Timepoint [2]
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Up to 60 months after CSL222 treatment
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Secondary outcome [3]
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Number of TEAEs
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Assessment method [3]
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Timepoint [3]
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Up to 60 months after CSL222 treatment
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Secondary outcome [4]
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Change in Liver ultrasound
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Assessment method [4]
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Timepoint [4]
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Up to 60 months after CSL222 treatment
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Secondary outcome [5]
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Number of participants who develop Factor IX (FIX) Inhibitors
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Assessment method [5]
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Timepoint [5]
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Up to 60 months after CSL222 treatment
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Secondary outcome [6]
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Percentage of participants who develop FIX Inhibitors
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Assessment method [6]
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Timepoint [6]
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Up to 60 months after CSL222 treatment
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Secondary outcome [7]
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Change in hematology and biochemistry parameters
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Assessment method [7]
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Timepoint [7]
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Up to 60 months after CSL222 treatment
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Secondary outcome [8]
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Number of participants with clinically significant increase in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)
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Assessment method [8]
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Timepoint [8]
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Up to 60 months after CSL222 treatment
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Secondary outcome [9]
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Percentage of participants with clinically significant increase in ALT or AST
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Assessment method [9]
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Timepoint [9]
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Up to 60 months after CSL222 treatment
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Secondary outcome [10]
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Corticosteroid use for ALT or AST increases after CSL222 treatment
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Assessment method [10]
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Timepoint [10]
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Up to 60 months after CSL222 treatment
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Secondary outcome [11]
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Number of participants with clinically significant Alpha-fetoprotein (AFP)
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Assessment method [11]
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Timepoint [11]
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Baseline and up to 60 months after CSL222 treatment
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Secondary outcome [12]
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Percentage of participants with clinically significant AFP
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Assessment method [12]
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Timepoint [12]
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Baseline and up to 60 months after CSL222 treatment
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Secondary outcome [13]
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Number of participants with infusion related reactions or hypersensitivity reactions
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Assessment method [13]
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Timepoint [13]
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Throughout CSL222 infusion period and up to 60 months after CSL222 treatment
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Secondary outcome [14]
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Percentage of participants with infusion related reactions or hypersensitivity reactions
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Assessment method [14]
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Timepoint [14]
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Throughout CSL222 infusion period and up to 60 months after CSL222 treatment
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Secondary outcome [15]
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Change in the Uncontaminated Endogenous FIX activity
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Assessment method [15]
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Timepoint [15]
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Baseline and up to Months 6, 12, and 18 after CSL222 treatment
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Secondary outcome [16]
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Annualized consumption of FIX replacement therapy
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Assessment method [16]
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Timepoint [16]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [17]
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Annualized infusion rate of FIX replacement therapy
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Assessment method [17]
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Timepoint [17]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [18]
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Number of participants remaining free of continuous FIX prophylaxis
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Assessment method [18]
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Timepoint [18]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [19]
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Percentage of participants remaining free of continuous FIX prophylaxis
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Assessment method [19]
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Timepoint [19]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [20]
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ABR for spontaneous bleeding episodes
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Assessment method [20]
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Timepoint [20]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [21]
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ABR for joint bleeding episodes
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Assessment method [21]
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Timepoint [21]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [22]
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ABR for FIX-treated bleeding episodes
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Assessment method [22]
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Timepoint [22]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [23]
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Correlation analysis of FIX activity levels with baseline AAV5 NAb titers
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Assessment method [23]
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Timepoint [23]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [24]
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Number of participants with new target joints and resolved pre-existing target joints
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Assessment method [24]
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Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint.
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Timepoint [24]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [25]
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Number of participants with zero bleeding episodes and zero FIX-treated bleeding episodes
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Assessment method [25]
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Timepoint [25]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [26]
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Percentage of participants with zero bleeding episodes and zero FIX-treated bleeding episodes
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Assessment method [26]
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Timepoint [26]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [27]
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Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score
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Assessment method [27]
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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.
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Timepoint [27]
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Baseline and up to 18 months after CSL222 treatment
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Secondary outcome [28]
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Change in the EQ-5D-5L Index Scores
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Assessment method [28]
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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.
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Timepoint [28]
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Baseline and up to 18 months after CSL222 treatment
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Secondary outcome [29]
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Number of Participants with Uncontaminated Endogenous FIX Activity of Greater than or Equal to (>=) 5%
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Assessment method [29]
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Timepoint [29]
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Months 7 to 18 after CSL222 treatment
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Secondary outcome [30]
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Percentage of Participants with Uncontaminated Endogenous FIX Activity of >= 5%
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Assessment method [30]
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Timepoint [30]
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Months 7 to 18 after CSL222 treatment
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Eligibility
Key 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 (less than or equal to [<=] 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 greater than (>) 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 adhere to contraception guidelines.
* 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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 (based on central laboratory results) of total bilirubin > 2 × the upper limit of normal (ULN) (except if caused by Gilbert's syndrome).
* Screening or Visit L-Final laboratory values (based on central laboratory results) of any of the following laboratory abnormalities:
1. ALT > 2 × the ULN
2. AST > 2 × the ULN
3. Alkaline phosphatase > 2 × the ULN
4. Serum creatinine > 2 × the ULN
5. Hemoglobin less than (<) 8 g/dL
* Any condition other than hemophilia B resulting in an increased bleeding tendency.
* Thrombocytopenia, defined as a platelet count <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 AAV5 gene therapy treatment.
* Receipt of an experimental agent or device within 60 days before Screening until the end of the study.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Not applicable
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
30/01/2024
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
2/04/2032
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Actual
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Sample size
Target
35
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
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Recruitment hospital [1]
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Royal Prince Alfred Hospital - 03600044 - Camperdown
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Recruitment hospital [2]
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Royal Brisbane Hospital - 03600045 - Herston
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Recruitment hospital [3]
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The Alfred Hospital - 03600043 - Melbourne
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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4029 - Herston
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Recruitment postcode(s) [3]
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3004 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Michigan
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Country [2]
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Canada
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State/province [2]
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Ontario
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Country [3]
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Hong Kong
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State/province [3]
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Hong Kong
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Country [4]
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Hong Kong
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State/province [4]
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Sha Tin
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Country [5]
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Israel
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State/province [5]
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Tel Hashomer
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Country [6]
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Korea, Republic of
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State/province [6]
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Daegu
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Country [7]
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Korea, Republic of
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State/province [7]
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Seoul
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Country [8]
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Mexico
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State/province [8]
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Distrito Federal
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Country [9]
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Saudi Arabia
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State/province [9]
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Riyadh
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Country [10]
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Singapore
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State/province [10]
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Singapore
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Country [11]
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South Africa
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State/province [11]
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Johannesburg
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Country [12]
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Taiwan
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State/province [12]
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Neihu District
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Country [13]
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Taiwan
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State/province [13]
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Sanmin District
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Country [14]
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Turkey
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State/province [14]
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Bornova
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Country [15]
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Turkey
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State/province [15]
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Gaziantep
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
CSL Behring
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT06003387
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Study Director
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Address
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CSL Behring
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Trial Registration Coordinator
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Address
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Country
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Phone
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1-610-878-4697
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT06003387
Download to PDF