Clinical trial • Phase III • Haematology

ETRANACOGENE DEZAPARVOVEC for Hemophilia B

Phase III trial of ETRANACOGENE DEZAPARVOVEC for Hemophilia B. open-label, none/not specified-controlled. 14 participants.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Hemophilia B
Trial Stage
Phase III
Drug Modality
Gene therapy
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
14-03-2025
First CTIS Authorization Date
15-07-2025

Trial design

open-label, none/not specified-controlled Phase III trial in Belgium, Austria, France and others.

Open Label
Yes
Comparator
None/Not specified
Target Sample Size
14
Trial Duration For Participant
2007

Eligibility

Recruits 14 paediatric patients.

Vulnerable Population
Includes adolescent participants (assigned male at birth) aged ≥12 to <18 years. The trial documentation includes age-specific assent and consent handling: adolescent assent forms (Assent 11-14 Years; Assent 15-17 Years), parental/guardian consent forms (Parent-Guardian, Main Parental, Holder of the Parental Authority) and separate adult ICFs; materials are provided in specific language versions (e.g., French and Dutch listed, and English protocol synopses available). Parental/guardian consent is required for minors and assent is obtained from adolescent participants per the provided assent forms.

Inclusion criteria

  • {"criterion_text":"- 1. Assigned male sex at birth."}
  • {"criterion_text":"- 2. Aged >=138 months (11 years and 6 months) to less than (<) 206 months (17 years and 2 months) at the time of informed consent / assent."}
  • {"criterion_text":"- 3. 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 has been on continuous FIX prophylaxis."}
  • {"criterion_text":"- 4. On stable FIX continuous prophylaxis for at least 2 months before Screening."}
  • {"criterion_text":"- 5. Minimum of 75 previous exposure days of treatment with FIX protein before Screening."}
  • {"criterion_text":"- 6. Additional Key Inclusion Criteria for the Treatment Period: Completed the Lead-in Period: minimum of 6 months (26 weeks) of lead-in data collected and eligibility has been confirmed."}
  • {"criterion_text":"- 7. Additional Key Inclusion Criteria for the Treatment Period: Aged >= 12 to < 18 years at the time of CSL222 treatment."}

Exclusion criteria

  • {"criterion_text":"- 1. History of FIX inhibitors or positive FIX inhibitor test at Screening (based on central laboratory results)."}
  • {"criterion_text":"- 2. Screening laboratory values (based on central laboratory results): ◦ Total bilirubin greater than (>) 2 x the upper limit of normal (ULN) ◦ ALT > 2 x the ULN. ◦ AST > 2 x the ULN. ◦ ALP > 2 x the ULN. ◦ Serum creatinine > 2 x the ULN. ◦ Hemoglobin < 8 g/dL."}
  • {"criterion_text":"- 3. Any condition other than hemophilia B resulting in an increased bleeding tendency."}
  • {"criterion_text":"- 4. Thrombocytopenia, defined as a platelet count below 50 x 10^9/Liter, at Screening (based on central laboratory results)."}
  • {"criterion_text":"- 5. Any uncontrolled or untreated infection (human immunodeficiency virus, hepatitis C, etc) or any other significant concurrent, uncontrolled medical condition, as evaluated by the investigator, 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":"- 6. Additional Key Exclusion Criteria for the Treatment Period: Positive FIX inhibitor test at Visit L-Final (based on central laboratory results)."}
  • {"criterion_text":"- 7. Additional Key Exclusion Criteria for the Treatment Period: AAV5 NAb titer > 1:900 as assessed at Visit LX (last visit before Visit L-Final)."}
  • {"criterion_text":"- 8. Additional Key Exclusion Criteria for the Treatment Period: Visit L-Final laboratory values (based on central laboratory results) of: ◦ Total bilirubin > 2 × the ULN ◦ ALT > 2 × the ULN. ◦ AST > 2 × the ULN. ◦ ALP > 2 × the ULN. ◦ Serum creatinine > 2 × the ULN. ◦ Hemoglobin < 8 g/dL."}
  • {"criterion_text":"- 9. Additional Key Exclusion Criteria for the Treatment Period: thrombocytopenia, defined as a platelet count below 50 × 10^9/L, at Visit L-Final (based on central laboratory results)."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Annualized Bleeding Rate (ABR)","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- 1. Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) total score and change from baseline. At baseline and Month 18 post treatment.","definition_or_measurement_approach":"Measured at baseline and Month 18 post treatment (timing specified)."}
  • {"endpoint_text":"- 2. Endogenous FIX activity","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 3. Change from baseline in endogenous FIX activity","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 4. Annualized consumption of FIX replacement therapy","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 5. Annualized infusion rate of FIX replacement therapy","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 6. Number of participants remaining free of continuous FIX prophylaxis","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 7. Percentage of participants remaining free of continuous FIX prophylaxis","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 8. ABR for spontaneous, joint, and FIX-treated bleeding episodes","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 9. Correlation of FIX activity levels and pre-CSL222 AAV5 NAb titer","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 10. Number of new target joints and resolution of preexisting target joints","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 11. Number of participants with zero bleeds and zero FIX-treated bleeds","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 12. Percentage of participants with zero bleeds and zero FIX-treated bleeds","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 13. Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 14. Change in the EQ-5D-5L Index Scores","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 15. Change in the Patient-Reported Outcomes Measurement Information System (PROMIS)-25 total score","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 16. Change from baseline in PROMIS-29 total score. At baseline, during the Lead-In Period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years).","definition_or_measurement_approach":"Measured at baseline, during lead-in (≥6 months) and up to 5 years posttreatment (timing specified)."}
  • {"endpoint_text":"- 17. Number of participants with endogenous FIX activity of => 5%","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 18. Percentage of participants with endogenous FIX activity of => 5%","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 19. Adverse events - number of participants","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 20. Adverse events - percentage of participants","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 21. Adverse events - number of events","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 22. Change in liver ultrasound","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 23. Number of participants with antibodies against AAV5","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 24. Number of participants who develop FIX inhibitors","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 25. Number of clinically significant clinical laboratory tests (Hematology and Biochemistry) reported as an AE","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 26. Number of participants with clinically significant ALT/AST levels","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 27. Percentage of participants with clinically significant ALT/AST levels","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 28. Number of participants using corticosteroid for change in AST/ALT levels","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 29. Duration of corticosteroid use for change in AST/ALT levels","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 30. Mean inflammatory markers values","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 31. Change from baseline in Inflammatory markers","definition_or_measurement_approach":""}

Recruitment

Registry Or Advocacy Recruitment
True, Center For Information And Study On Clinical Research Participation Inc.
Digital Remote Recruitment
True, includes a Study Portal (site-facing and patient-facing) and electronic recruitment/consent navigation materials (Consent Navigator documents).
Planned Sample Size
14
Recruitment Window Months
99
Consent Approach
Informed consent and assent procedures are age-specific: parental/guardian consent required for minors with dedicated parent/guardian consent forms; adolescent assent forms available (Assent 11-14 Years; Assent 15-17 Years). Separate adult ICFs and pregnant-partner information/forms are provided. Documents exist in country/language-specific versions (examples include French and Dutch versions and English protocol synopses). Contact/email for trial registration and site contacts provided (e.g., clinicaltrials@cslbehring.com).

Methods

  • Use of recruitment arrangements and materials (documents titled 'K1_Recruitment arrangements' and 'K2_Recruitment Material' including Consent Navigator, Patient Journey Map, Patient Education Handouts) targeted at patients and caregivers.
  • Patient-facing study portal and site-facing portal (Study Portal: Site facing and Patient facing) for study information and training (Advarra responsibility).
  • Patient concierge services to support enrollment/retention (Block Clinical Inc. responsibility).
  • Patient educational, enrollment and retention materials and Patient Advisory Board involvement (Center For Information And Study On Clinical Research Participation Inc.).

Geography

Total Number Of Sites
6
Total Number Of Participants
6

Belgium

Earliest CTIS Part Ii Submission Date
02-06-2025
Latest Decision Or Authorization Date
19-02-2026
Processing Time Days
262
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
UZ Leuven
Department Name
Department of Pediatric Hematology and Oncology
Contact Person Name
Veerle Labarque
Contact Person Email
veerle.labarque@uzleuven.be
Number Of Participants
1

Austria

Earliest CTIS Part Ii Submission Date
11-06-2025
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
257
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Medical University Of Vienna
Department Name
Department of Paediatrics and Adolescent Medicine
Contact Person Name
Christoph Male-Dressler
Number Of Participants
1

France

Earliest CTIS Part Ii Submission Date
23-06-2025
Latest Decision Or Authorization Date
03-03-2026
Processing Time Days
253
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Hemostasis and Transfusion Department, Institut Cœur Poumon
Contact Person Name
Antoine Rauch
Contact Person Email
antoine.rauch@chu-lille.fr
Number Of Participants
1
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Pediatric Haematology, Immunology and Oncology Department
Contact Person Name
Herve Chambost
Contact Person Email
herve.chambost@ap-hm.fr
Number Of Participants
1

Spain

Earliest CTIS Part Ii Submission Date
05-05-2025
Latest Decision Or Authorization Date
11-02-2026
Processing Time Days
282
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
Hospital Universitario La Paz
Department Name
Hematology
Contact Person Name
Víctor Manuel Jiménez Yuste
Contact Person Email
vjyuste.ensayos@gmail.com
Number Of Participants
1
Site Name
Hospital Sant Joan De Deu Barcelona
Department Name
Pediatric - Hematologic
Contact Person Name
Rubén Berrueco Moreno
Contact Person Email
ruben.berrueco@sjd.es
Number Of Participants
1

Sponsor

Primary sponsor

Full Name
CSL Behring LLC
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Suvoda LLC
Responsibilities
sponsorDuties codes: 3
Name
Block Clinical Inc.
Responsibilities
Patient concierge services
Name
Scarritt Group Inc.
Responsibilities
Organization of the Investigators Meetings (IM)
Name
Drugdev Inc.
Responsibilities
Site payment
Name
Precision For Medicine Inc.
Responsibilities
sponsorDuties codes: 4
Name
Advarra Inc.
Responsibilities
Study Portal: Site facing and Patient facing, Site Study Specific Training

Third parties

  • {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long term sample storage","organisation_type":"Pharmaceutical company"}
  • {"country":"Denmark","full_name":"Unilabs A/S","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Psi Cro AG","duties_or_roles":"sponsorDuties codes: 1, 12, 5, 8","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Advarra Inc.","duties_or_roles":"Study Portal: Site facing and Patient facing, Site Study Specific Training","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Center For Information And Study On Clinical Research Participation Inc.","duties_or_roles":"Patient Educational, Enrollment and Retention Materials, Patient Advisory Board","organisation_type":"Patient organisation/association"}
  • {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"Organization of the Investigators Meetings (IM)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Atorus Research Inc.","duties_or_roles":"sponsorDuties codes: 6","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Preventiongenetics LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Block Clinical Inc.","duties_or_roles":"Patient concierge services","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Drugdev Inc.","duties_or_roles":"Site payment","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"ProtaGene CGT GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Charles River Laboratories Edinburgh Limited","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Off-Site Research Nursing Services","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
Hemgenix 1x10^13 genome copies/mL concentrate for solution for infusion
Active Substance
ETRANACOGENE DEZAPARVOVEC
Modality
Gene therapy
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation EU/1/22/1715/001)
Orphan Designation
Yes
Starting Dose
Single intravenous infusion of 2 × 10^13 genome copies per kilogram of body weight (gc/kg)
Dose Levels
Single-dose: 2 × 10^13 gc/kg
Frequency
Single-dose
Maximum Dose
2 millilitre(s)/kilogram (maxTotalDoseAmount from product record)

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