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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
15/01/2025

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)
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
Secondary ID [1] 0 0
2023-509590-23-00
Secondary ID [2] 0 0
CSL222_3005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia B 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Bleeding Rate (ABR)
Timepoint [1] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [1] 0 0
Number of participants with Treatment Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Up to 18 months after CSL222 treatment
Secondary outcome [2] 0 0
Percentage of participants with TEAEs
Timepoint [2] 0 0
Up to 18 months after CSL222 treatment
Secondary outcome [3] 0 0
Number of TEAEs
Timepoint [3] 0 0
Up to 18 months after CSL222 treatment
Secondary outcome [4] 0 0
Change in Liver ultrasound
Timepoint [4] 0 0
Baseline and up to 18 months after CSL222 treatment
Secondary outcome [5] 0 0
Number of participants who develop Factor IX (FIX) Inhibitors
Timepoint [5] 0 0
Up to 18 months after CSL222 treatment
Secondary outcome [6] 0 0
Percentage of participants who develop FIX Inhibitors
Timepoint [6] 0 0
Up to 18 months after CSL222 treatment
Secondary outcome [7] 0 0
Change in hematology and biochemistry parameters
Timepoint [7] 0 0
Baseline and up to 18 months after CSL222 treatment
Secondary outcome [8] 0 0
Number of participants with clinically significant increase in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)
Timepoint [8] 0 0
Up to 18 months after CSL222 treatment
Secondary outcome [9] 0 0
Percentage of participants with clinically significant increase in ALT or AST
Timepoint [9] 0 0
Up to 18 months after CSL222 Treatment
Secondary outcome [10] 0 0
Corticosteroid use for ALT or AST increases after CSL222 treatment
Timepoint [10] 0 0
Up to 18 months after CSL222 treatment
Secondary outcome [11] 0 0
Number of participants with clinically significant Alpha-fetoprotein (AFP)
Timepoint [11] 0 0
Baseline and up to 18 months after CSL222 treatment
Secondary outcome [12] 0 0
Percentage of participants with clinically significant AFP
Timepoint [12] 0 0
Baseline and up to 18 months after CSL222 treatment
Secondary outcome [13] 0 0
Number of participants with infusion related reactions or hypersensitivity reactions
Timepoint [13] 0 0
Throughout CSL222 infusion period and up to 18 months after CSL222 treatment
Secondary outcome [14] 0 0
Percentage of participants with infusion related reactions or hypersensitivity reactions
Timepoint [14] 0 0
Throughout CSL222 infusion period and up to 18 months after CSL222 treatment
Secondary outcome [15] 0 0
Change in the Endogenous FIX activity
Timepoint [15] 0 0
Baseline and up to Months 6, 12, and 18 after CSL222 treatment
Secondary outcome [16] 0 0
Annualized consumption of FIX replacement therapy
Timepoint [16] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [17] 0 0
Annualized infusion rate of FIX replacement therapy
Timepoint [17] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [18] 0 0
Number of participants remaining free of continuous routine FIX prophylaxis
Timepoint [18] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [19] 0 0
Percentage of participants remaining free of continuous routine FIX prophylaxis
Timepoint [19] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [20] 0 0
ABR for spontaneous bleeding episodes
Timepoint [20] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [21] 0 0
ABR for joint bleeding episodes
Timepoint [21] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [22] 0 0
ABR for FIX-treated bleeding episodes
Timepoint [22] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [23] 0 0
Correlation analysis of FIX activity levels with baseline AAV5 NAb titers
Timepoint [23] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [24] 0 0
Number of participants with new target joints and resolved preexisting target joints
Timepoint [24] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [25] 0 0
Number of participants with zero bleeds and zero FIX-treated bleeds
Timepoint [25] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [26] 0 0
Percentage of participants with zero bleeds and zero FIX-treated bleeds
Timepoint [26] 0 0
Months 7 to 18 after CSL222 treatment
Secondary outcome [27] 0 0
Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score
Timepoint [27] 0 0
Baseline and up to 18 months after CSL222 treatment
Secondary outcome [28] 0 0
Change in the EQ-5D-5L Index Scores
Timepoint [28] 0 0
Baseline and up to 18 months after CSL222 treatment

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 (= 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/10/2028
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - 03600044 - Camperdown
Recruitment hospital [2] 0 0
Royal Brisbane Hospital - 03600045 - Herston
Recruitment hospital [3] 0 0
The Alfred Hospital - 03600043 - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Michigan
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Israel
State/province [3] 0 0
Tel Hashomer
Country [4] 0 0
Korea, Republic of
State/province [4] 0 0
Daegu
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Seoul
Country [6] 0 0
Mexico
State/province [6] 0 0
Distrito Federal
Country [7] 0 0
Saudi Arabia
State/province [7] 0 0
Riyadh
Country [8] 0 0
South Africa
State/province [8] 0 0
Johannesburg

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
CSL Behring
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/study/NCT06003387
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
CSL Behring
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Registration Coordinator
Address 0 0
Country 0 0
Phone 0 0
1-610-878-4697
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06003387