Phase 3, Open-label, Single-dose Study of CSL222 in Adolescent Male Subjects (≥ 12 to < 18 Years of Age) with Severe or Moderately Severe Hemophilia B

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CSL Behring LLC

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

27 May 2026 → ongoing

Decision date (initial)

2025-07-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

CSL Behring LLC

External identifiers

EU CT number

2023-505805-18-00

ClinicalTrials.gov

NCT07080905

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The objective of this study is to investigate the efficacy, safety, and tolerability of CSL222 (International Nonproprietary Name: etranacogene dezaparvovec, previously termed AMT 061) administered to adolescent male subjects (≥ 12 to < 18 years of age) with severe or moderately severe hemophilia B.

Conditions and MedDRA coding

Hemophilia B

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002722-PIP01-19

Plan to share IPD

Yes

IPD plan description

CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at [email protected].

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Assigned male sex at birth.
2. 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.
3. 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.
4. 4. On stable FIX continuous prophylaxis for at least 2 months before Screening.
5. 5. Minimum of 75 previous exposure days of treatment with FIX protein before Screening.
6. 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.
7. 7. Additional Key Inclusion Criteria for the Treatment Period: Aged >= 12 to < 18 years at the time of CSL222 treatment.

Exclusion criteria 9

1. 1. History of FIX inhibitors or positive FIX inhibitor test at Screening (based on central laboratory results).
2. 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.
3. 3. Any condition other than hemophilia B resulting in an increased bleeding tendency.
4. 4. Thrombocytopenia, defined as a platelet count below 50 x 10^9/Liter, at Screening (based on central laboratory results).
5. 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.
6. 6. Additional Key Exclusion Criteria for the Treatment Period: Positive FIX inhibitor test at Visit L-Final (based on central laboratory results).
7. 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).
8. 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.
9. 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 and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized Bleeding Rate (ABR)

Secondary endpoints 31

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CSL Behring LLC

Sponsor organisation

CSL Behring LLC

Address

1020 1st Avenue

City

King Of Prussia

Postcode

19406-1310

Country

United States

Scientific contact point

Organisation

CSL Behring LLC

Contact name

Study Director

Public contact point

Organisation

CSL Behring LLC

Contact name

Trial Registration Coordinator

Third parties 18

Locations

4 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 67 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications