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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

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
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 D.


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
Post-dose: Months 7 to 18
Secondary outcome [1] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs), and TEAEs of Special Interest (TEAESIs)
Timepoint [1] 0 0
Post-dose: At Months 6,12, and 18
Secondary outcome [2] 0 0
Percentage of Participants With TEAEs, TESAEs, and TEAESIs
Timepoint [2] 0 0
Post-dose: At Months 6,12, and 18
Secondary outcome [3] 0 0
Number of TEAEs, TESAEs, and TEAESIs
Timepoint [3] 0 0
Post-dose: At Months 6,12, and 18
Secondary outcome [4] 0 0
Number of Participants with Change From Baseline in Abdominal Ultrasound
Timepoint [4] 0 0
Baseline up to 18 months post dose
Secondary outcome [5] 0 0
Number of Participants Who Develop Factor IX (FIX) Inhibitors
Timepoint [5] 0 0
Up to 18 months post dose
Secondary outcome [6] 0 0
Percentage of Participants who Develop FIX Inhibitors
Timepoint [6] 0 0
Up to 18 months post dose
Secondary outcome [7] 0 0
Number of Participants with Clinically Significant Hematology and Serum Chemistry Parameters
Timepoint [7] 0 0
Up to 18 months post dose
Secondary outcome [8] 0 0
Percentage of Participants With Clinically Significant Hematology and Serum Chemistry Parameters
Timepoint [8] 0 0
Up to 18 months post dose
Secondary outcome [9] 0 0
Number of Participants with Clinically Significant Change in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)
Timepoint [9] 0 0
Up to 18 months post dose
Secondary outcome [10] 0 0
Percentage of Participants With Clinically Significant Change in ALT or AST
Timepoint [10] 0 0
Up to 18 months post dose
Secondary outcome [11] 0 0
Number of Participants Treated With Corticosteroids For Change in ALT or AST
Timepoint [11] 0 0
Up to 18 months post dose
Secondary outcome [12] 0 0
Percentage of Participants Treated With Corticosteroids For Change in ALT or AST
Timepoint [12] 0 0
Up to 18 months post dose
Secondary outcome [13] 0 0
Number of Participants With Clinically Significant Alpha-fetoprotein (AFP)
Timepoint [13] 0 0
Up to 18 months post dose
Secondary outcome [14] 0 0
Percentage of Participants With Clinically Significant AFP
Timepoint [14] 0 0
Up to 18 months post dose
Secondary outcome [15] 0 0
Number of Participants with Infusion Related Reactions or Hypersensitivity Reactions
Timepoint [15] 0 0
Up to 18 months post dose
Secondary outcome [16] 0 0
Percentage of Participants With Infusion Related Reactions or Hypersensitivity Reactions
Timepoint [16] 0 0
Up to 18 months post dose
Secondary outcome [17] 0 0
Number of Participants With the Endogenous FIX Activity
Timepoint [17] 0 0
Post-dose: At Months 6, 12, and 18
Secondary outcome [18] 0 0
Change From Baseline in the Endogenous FIX Activity
Timepoint [18] 0 0
Baseline up to Months 6, 12, and 18 post dose
Secondary outcome [19] 0 0
Annualized Consumption of FIX Replacement Therapy
Timepoint [19] 0 0
Post-dose: Months 7 to 18
Secondary outcome [20] 0 0
Annualized Infusion Rate of FIX Replacement Therapy
Timepoint [20] 0 0
Post-dose: Months 7 to 18
Secondary outcome [21] 0 0
Percentage of Participants Remaining Free of Previous Continuous Routine FIX Prophylaxis
Timepoint [21] 0 0
Post-dose: Months 7 to 18
Secondary outcome [22] 0 0
ABR for Spontaneous Bleeding Episodes, Joint Bleeding Episodes, and FIX-treated Bleeding Episodes Separately
Timepoint [22] 0 0
Post-dose: Months 7 to 18
Secondary outcome [23] 0 0
Correlation Analysis of FIX Activity Levels
Timepoint [23] 0 0
Post-dose: Months 6 to 18
Secondary outcome [24] 0 0
Number of Participants With New Target Joints and Resolved New or Preexisting Target Joints
Timepoint [24] 0 0
Post-dose: Months 7 to 18
Secondary outcome [25] 0 0
Number of Participants With Zero Bleeds Following Stable FIX Expression
Timepoint [25] 0 0
Post-dose: Months 7 to 18
Secondary outcome [26] 0 0
Percentage of Participants With Zero Bleeds Following Stable FIX Expression
Timepoint [26] 0 0
Post-dose: Months 7 to 18
Secondary outcome [27] 0 0
Hemophilia Quality of Life Questionnaire (Hem-A-QoL) Total Score and Treatment Domain Score
Timepoint [27] 0 0
Post-dose: Months 6 to 18
Secondary outcome [28] 0 0
Change From Baseline in the Hem-A-QoL Total Score and Treatment Domain Score
Timepoint [28] 0 0
Baseline, Months 6 to 18 post dose
Secondary outcome [29] 0 0
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score
Timepoint [29] 0 0
Post-dose: Months 6 to 18
Secondary outcome [30] 0 0
EQ-5D-5L Index Scores
Timepoint [30] 0 0
Post-dose: Months 6 to 18
Secondary outcome [31] 0 0
Change from Baseline in the EQ-5D-5L VAS Score
Timepoint [31] 0 0
Baseline, Months 6 to 18 post dose
Secondary outcome [32] 0 0
Change From Baseline in the EQ-5D-5L Index Scores
Timepoint [32] 0 0
Baseline, Months 6 to 18 post dose

Eligibility
Key inclusion criteria
* 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 Screening or Visit L (lead-in period)-Final (based on central laboratory results)
* 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)
* ALT > 2 × the upper limit of normal (ULN) at Screening and Visit L-Final (based on central laboratory results)
* Any condition other than hemophilia B resulting in an increased bleeding tendency
* Any uncontrolled or untreated infection (human immunodeficiency virus [HIV], hepatitis C, etc.) or any other significant concurrent, uncontrolled medical condition evaluated by the investigator to interfere with adherence to the clinical study protocol or with the degree of tolerance to CSL222.
* Thrombocytopenia, defined as a platelet count below 50 × 10^9/L, at Screening and Visit L-Final (based on central laboratory results)
* Known history of allergy to corticosteroids or known medical condition that would require chronic administration of steroids.
* Known uncontrolled allergic conditions or allergy / hypersensitivity to any component of the CSL222 excipients
* Previous gene therapy treatment
* Receipt of an experimental agent or device within 60 days before Screening until the end of the study.
* Note: Other protocol pre-specified exclusion criteria may apply.

Study design
Purpose of the study
Prevention
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
1/10/2028
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
Saudi Arabia
State/province [6] 0 0
Riyadh
Country [7] 0 0
South Africa
State/province [7] 0 0
Johannesburg

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
CSL Behring LLC
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
clinicaltrials@cslbehring.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
Available to whom?
Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.
Available for what types of analyses?
How or where can data be obtained?


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