Single-dose CSL222 gene therapy for adolescent males (12–17) with severe or moderately severe hemophilia B.

Phase 3, Open-label, Single-dose, Multicenter Study Investigating Efficacy, Safety, and Tolerability of CSL222 (Etranacogene Dezaparvovec) Administered to Adolescent Male Subjects (≥ 12 to < 18 Years of Age) With Severe or Moderately Severe Hemophilia B

This will give a single dose of CSL222 gene therapy to adolescent males with severe or moderately severe hemophilia B to see if it raises factor IX activity and reduces bleeding.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 138 Months to 206 Months
• Sex: Male
• Sponsor: CSL Behring (Industry-sponsored)
• Locations: 11 sites (Orange, California and 10 other locations)
• Trial ID: NCT07080905 on ClinicalTrials.gov

What this trial studies

This is a phase 3, open-label, single-arm, single-dose, multicenter study administering CSL222 (AAV5-hFIXco-Padua) to adolescent males with severe or moderately severe hemophilia B. Eligible participants are males aged 12 to less than 18 with FIX activity ≤2% who have been on stable prophylactic FIX and have at least 75 prior exposure days, and they must complete a minimum 6-month lead-in period. After lead-in confirmation, participants receive a single infusion of CSL222 and are followed for safety, tolerability, and changes in FIX activity and bleeding outcomes. The study is conducted at U.S. centers and collects efficacy and safety data over planned follow-up visits after treatment.

Who should consider this trial

Good fit: Adolescent males aged 12 to less than 18 with congenital severe or moderately severe hemophilia B (FIX ≤2%), who have had ≥75 prior exposure days to FIX, have been on stable prophylaxis, and complete the required lead-in period.

Not a fit: Patients with a history of FIX inhibitors or a positive inhibitor test at screening, those who cannot complete the lead-in requirements, or who have other disqualifying safety issues are not likely to receive benefit from participation.

Why it matters

Potential benefit: If successful, a single CSL222 infusion could increase circulating FIX levels, lower bleeding rates, and reduce or eliminate the need for regular factor infusions in treated adolescents.

How similar studies have performed: AAV‑based FIX Padua gene therapies have produced sustained increases in FIX activity and reduced bleeding in adult trials, leading to regulatory approval for adults, but data in adolescents are still limited.

Eligibility criteria

Inclusion Criteria:

* Key Inclusion Criteria for the Lead-in Period:

Assigned male sex at birth

* 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.
* 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.
* On stable continuous FIX prophylaxis for at least 2 months before Screening.
* Minimum of 75 previous exposure days of treatment with FIX protein before Screening.
* 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.

* Aged ≥ 12 to \< 18 years at the time of CSL222 treatment.

Exclusion Criteria:

* Key Exclusion Criteria for the Lead-in Period:

History of FIX inhibitors or positive FIX inhibitor test at Screening (based on central laboratory results).

* Screening laboratory values (based on central laboratory results):

  * Total bilirubin \> 2 × the upper limit of normal (ULN).
  * Alanine aminotransferase (ALT) \> 2 × the ULN.
  * Aspartate aminotransferase (AST) \> 2 × the ULN.
  * Alkaline phosphatase (ALP) \> 2 × the ULN.
  * Serum creatinine \> 2 × the ULN.
  * Hemoglobin \< 8 g/dL.
* Any condition other than hemophilia B resulting in an increased bleeding tendency.
* Thrombocytopenia, defined as a platelet count below 50 × 10\^9/L, at screening (based on central laboratory results).
* 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.
* Additional Key Exclusion Criteria for the Treatment Period:

Positive FIX inhibitor test at Visit L-Final (based on central laboratory results)

* AAV5 NAb titer \> 1:900 as assessed at Visit LX (last visit before Visit L-Final).
* 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.
* Thrombocytopenia, defined as a platelet count below 50 × 10\^9/L, at Visit L-Final (based on central laboratory results).

Where this trial is running

Orange, California and 10 other locations

• Center for Inherited Blood Disorders — Orange, California, United States (Recruiting)
• University of Florida — Gainesville, Florida, United States (Recruiting)
• Arthur M. Blank Hospital - Children's Healthcare of Atlanta — Atlanta, Georgia, United States (Recruiting)
• University of Michigan Medical Center — Ann Arbor, Michigan, United States (Recruiting)
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)
• Medical University Vienna — Vienna, Austria (Recruiting)
• UZ Leuven - Centrum voor Moleculaire en Vasculaire Biologie — Leuven, Belgium (Recruiting)
• Chaim Sheba Medical Center — Ramat Gan, Israel (Recruiting)
• La Paz University Hospital — Madrid, Spain (Recruiting)
• St Thomas Hospital — London, United Kingdom (Recruiting)
• John Radcliffe Hospital - Oxford University Hospitals NHS — Oxford, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Trial Registration Coordinator

Conditions Hemophilia B