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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CSL Behring LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

22 Apr 2026 → ongoing

Decision date (initial)

2025-01-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

CSL Behring LLC

External identifiers

EU CT number

2023-509590-23-00

ClinicalTrials.gov

NCT06003387

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

The primary objective of this study is to assess whether there is a clinically significant correlation of pretreatment AAV5 NAb titers on the risk of bleeding during the 52 weeks following CSL222 treatment after the establishment of stable FIX expression (Months 7 to 18 postdose) compared to standard of care continuous routine FIX prophylaxis during the ≥ 6-month Lead-in Period.

Conditions and MedDRA coding

Hemophilia B

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1) Age ≥ 18 years and considered legally an adult, as defined by country regulations.
2. 2) 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 subject is on continuous routine FIX prophylaxis.
3. 3) 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).
4. 4) Has greater than (>) 150 previous exposure days to FIX replacement therapy
5. 5) Has been on stable FIX prophylaxis for at least 2 months before Screening.
6. 6) Has demonstrated capability to independently, accurately, and in a timely manner complete the eDiary during the Lead-in Period, as judged by the investigator.
7. 7) Acceptance to adhere to contraception
8. 8) Able to provide informed consent after receipt of verbal and written information about the study.
9. 9) 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.

Exclusion criteria 10

1. 1) History of FIX inhibitors or positive FIX inhibitor test at Prescreening, Screening or Visit L-Final (based on central laboratory results).
2. 2) 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).
3. 3) Screening or Visit L-Final laboratory values (based on central laboratory results).of any of the following laboratory abnormalities: • Alanine aminotransferase (ALT) > 2 × the ULN • Aspartate aminotransferase (AST) > 2 × the ULN • Alkaline phosphatase > 2 × the ULN • Serum creatinine > 2 × the ULN • Hemoglobin < 8 g/dL
4. 4) Any condition other than hemophilia B resulting in an increased bleeding tendency.
5. 5) Thrombocytopenia, defined as a platelet count 50 × 10^9/L, at Screening or Visit L-Final (based on central laboratory results).
6. 6) 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.
7. 7) Known history of allergy to corticosteroids or known medical condition that would require chronic administration of oral corticosteroids.
8. 8) 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).
9. 9) Previous gene therapy treatment.
10. 10) Receipt of an experimental agent or device within 60 days before Screening until the end of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized bleeding rate (ABR)

Secondary endpoints 30

1. 1) Number of participants with Treatment Emergent Adverse Events (TEAEs).
2. 2) Percentage of participants with TEAEs.
3. 3) Number of TEAEs.
4. 4) Change in Liver ultrasound.
5. 5) Number of participants who develop Factor IX (FIX) Inhibitors.
6. 6) Percentage of participants who develop Factor IX (FIX) Inhibitors.
7. 7) Change in hematology and biochemistry parameters.
8. 8) Number of participants with clinically significant increase in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST).
9. 9) Percentage of participants with clinically significant increase in ALT or AST.
10. 10) Corticosteroid use for ALT or AST increases after CSL222 treatment.
11. 11) Number of participants with clinically significant Alpha-fetoprotein (AFP).
12. 12) Percentage of participants with clinically significant AFP.
13. 13) Number of participants with infusion related reactions or hypersensitivity reactions.
14. 14) Percentage of participants with infusion related reactions or hypersensitivity reactions.
15. 15) Change in the Uncontaminated Endogenous FIX activity.
16. 16)Annualized consumption of FIX replacement therapy.
17. 17) Annualized infusion rate of FIX replacement therapy.
18. 18) Number of participants remaining free of continuous routine FIX prophylaxis.
19. 19) Percentage of participants remaining free of continuous FIX prophylaxis.
20. 20) ABR for spontaneous bleeding episodes.
21. 21) ABR for joint bleeding episodes.
22. 22) ABR for FIX-treated bleeding episodes.
23. 23) Correlation analysis of FIX activity levels with baseline AAV5 NAb titers.
24. 24) Number of participants with new target joints and resolved preexisting target joints.
25. 25) Number of participants with zero bleeding episodes and zero FIX-treated bleeding episodes .
26. 26) Percentage of participants with zero bleeding episodes and zero FIX-treated bleeding episodes
27. 27) Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score.
28. 28) Change in the EQ-5D-5L Index Scores.
29. 29) Number of paticipant with Uncontaminated Endogenous FIX Activity of greater than or equal to >=5%
30. 30) Percentage of participant with Uncontaminated Endogenous FIX Activity of >=5%

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 14

Locations

2 EU/EEA countries · 2 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 30 files

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

Application history

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