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Efficacy and Safety of CSL222 (Etranacogene Dezaparvovec) Gene Therapy in Adults with Hemophilia B with Pretreatment AAV5 Neutralizing Antibodies.

Phase 3
Not yet recruiting
Conditions
Hemophilia B
Interventions
Genetic: CSL222 (AAV5-hFIXco-Padua)
Registration Number
2023-509590-23-00
Lead Sponsor
CSL Behring LLC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised, recruitment pending
Sex
Not specified
Target Recruitment
2
Inclusion Criteria
  1. Age ≥ 18 years and considered legally an adult, as defined by country regulations.

  2. Has congenital hemophilia B with known severe or moderately severe FIX deficiency (≤ 2% of normal circulating FIX) for which the subject is on continuous routine FIX prophylaxis.

  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. Has > 150 previous exposure days to FIX replacement therapy.

  5. Has been on stable FIX prophylaxis for at least 2 months before Screening.

  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. Acceptance to barrier contraception protection for 1 year starting the day of CSL222 treatment.

  8. Able to provide informed consent after receipt of verbal and written information about the study.

  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
  1. History of FIX inhibitors or positive FIX inhibitor test at Prescreening, Screening or Visit L-Final (based on central laboratory results).

  2. Receipt of an experimental agent or device within 60 days before Screening until the end of the study.

  3. 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).

  4. ALT > 2 × the ULN at Screening or Visit L-Final laboratory values (based on central laboratory results).

  5. Any condition other than hemophilia B resulting in an increased bleeding tendency.

  6. Thrombocytopenia, defined as a platelet count below 50 × 10^9/L, at Screening or Visit L-Final (based on central laboratory results).

  7. 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.

  8. Known history of allergy to corticosteroids or known medical condition that would require chronic administration of oral corticosteroids.

  9. 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).

  10. Previous gene therapy treatment.

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
CSL222CSL222 (AAV5-hFIXco-Padua)Participants will receive CSL222 as a single intravenous (IV) infusion of 2 × 10\^13 genome copies per kilogram (gc/kg) on Day D.
Primary Outcome Measures
NameTimeMethod
Annualized bleeding rate (ABR)

Annualized bleeding rate (ABR)

Secondary Outcome Measures
NameTimeMethod
1) Number of participants with Treatment Emergent Adverse Events (TEAEs).

1) Number of participants with Treatment Emergent Adverse Events (TEAEs).

2) Percentage of participants with TEAEs.

2) Percentage of participants with TEAEs.

3) Number of TEAEs.

3) Number of TEAEs.

4) Change in Liver ultrasound.

4) Change in Liver ultrasound.

5) Number of participants who develop Factor IX (FIX) Inhibitors.

5) Number of participants who develop Factor IX (FIX) Inhibitors.

6) Percentage of participants who develop Factor IX (FIX) Inhibitors.

6) Percentage of participants who develop Factor IX (FIX) Inhibitors.

7) Change in hematology and biochemistry parameters.

7) Change in hematology and biochemistry parameters.

8) Number of participants with clinically significant increase in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST).

8) Number of participants with clinically significant increase in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST).

9) Percentage of participants with clinically significant increase in ALT or AST.

9) Percentage of participants with clinically significant increase in ALT or AST.

10) Corticosteroid use for ALT or AST increases after CSL222 treatment.

10) Corticosteroid use for ALT or AST increases after CSL222 treatment.

11) Number of participants with clinically significant Alpha-fetoprotein (AFP).

11) Number of participants with clinically significant Alpha-fetoprotein (AFP).

12) Percentage of participants with clinically significant AFP.

12) Percentage of participants with clinically significant AFP.

13) Number of participants with infusion related reactions or hypersensitivity reactions.

13) Number of participants with infusion related reactions or hypersensitivity reactions.

14) Percentage of participants with infusion related reactions or hypersensitivity reactions.

14) Percentage of participants with infusion related reactions or hypersensitivity reactions.

15) Change in the Endogenous FIX activity.

15) Change in the Endogenous FIX activity.

16)Annualized consumption of FIX replacement therapy.

16)Annualized consumption of FIX replacement therapy.

17) Annualized infusion rate of FIX replacement therapy.

17) Annualized infusion rate of FIX replacement therapy.

18) Number of participants remaining free of continuous routine FIX prophylaxis.

18) Number of participants remaining free of continuous routine FIX prophylaxis.

19) Percentage of participants remaining free of continuous routine FIX prophylaxis.

19) Percentage of participants remaining free of continuous routine FIX prophylaxis.

20) ABR for spontaneous bleeding episodes.

20) ABR for spontaneous bleeding episodes.

21) ABR for joint bleeding episodes.

21) ABR for joint bleeding episodes.

22) ABR for FIX-treated bleeding episodes.

22) ABR for FIX-treated bleeding episodes.

23) Correlation analysis of FIX activity levels with baseline AAV5 NAb titers.

23) Correlation analysis of FIX activity levels with baseline AAV5 NAb titers.

24) Number of participants with new target joints and resolved preexisting target joints.

24) Number of participants with new target joints and resolved preexisting target joints.

25) Number of participants with zero bleeds and zero FIX-treated bleeds.

25) Number of participants with zero bleeds and zero FIX-treated bleeds.

26) Percentage of participants with zero bleeds and zero FIX-treated bleeds.

26) Percentage of participants with zero bleeds and zero FIX-treated bleeds.

27) Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score.

27) Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score.

28) Change in the EQ-5D-5L Index Scores.

28) Change in the EQ-5D-5L Index Scores.

Trial Locations

Locations (2)

Specialized Hospital For Active Treatment Of Hematological Diseases EAD

🇧🇬

Sofiya, Bulgaria

Instytut Hematologii I Transfuzjologii

🇵🇱

Warsaw, Poland

Specialized Hospital For Active Treatment Of Hematological Diseases EAD
🇧🇬Sofiya, Bulgaria
Toshko Lissitchov
Site contact
024542235
t_lissitchkov@yahoo.com
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