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

Official title

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

Overview

This is a phase 3, prospective, open-label, single-arm, single-dose, multicenter study investigating the efficacy, safety, and tolerability of CSL222 (AAV5-hFIXco-Padua) in adolescent male participants with severe or moderately severe hemophilia B.

Interventions

• Genetic CSL222 (Adeno-associated viral vector serotype 5 [AAV5]-hFIXco-Padua)
  Administered as a single IV infusion.

Primary outcome measures

• Annualized Bleeding Rate (ABR) [Time frame: For the Lead-In Period (at least 6 months) and for the 52 weeks after stable FIX expression (months 7 to 18 after treatment with CSL222)]

Secondary outcome measures (12)

• Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) total score and change from baseline [Time frame: At baseline and Month 18 post treatment]
• Endogenous FIX activity [Time frame: At baseline, and at months 6, 12, and 18 after treatment with CSL222]
• Change from baseline in endogenous FIX activity [Time frame: At baseline, and at months 6, 12, and 18 after treatment with CSL222]
• Annualized consumption of FIX replacement therapy [Time frame: For the Lead-In Period (at least 6 months), for the 52 weeks following stable FIX expression (months 7 to 18 after treatment with CSL222), and annually in the Posttreatment Follow-up Period (up to 5 years)]
• Annualized infusion rate of FIX replacement therapy [Time frame: For the Lead-In Period (at least 6 months), for the 52 weeks following stable FIX expression (months 7 to 18 after treatment with CSL222), and annually in the Posttreatment Follow-up Period (up to 5 years)]
• Number of participants remaining free of continuous FIX prophylaxis [Time frame: During the 52 weeks after stable FIX expression (months 7 to 18 after treatment with CSL222), and during months 7 to: 24, 36, 48, and 60 after treatment with CSL222]
• Percentage of participants remaining free of continuous FIX prophylaxis [Time frame: During the 52 weeks after stable FIX expression (months 7 to 18 after treatment with CSL222), and during months 7 to: 24, 36, 48, and 60 after treatment with CSL222]
• ABR for spontaneous, joint, and FIX-treated bleeding episodes [Time frame: For the Lead-In Period (at least 6 months) and during the 52 weeks after stable FIX expression (months 7 to 18 after treatment with CSL222)]
• Correlation of FIX activity levels and pre-CSL222 AAV5 NAb titer [Time frame: At the end of the Lead-in Period and during 6 to 18 months after treatment with CSL222]
• Number of new target joints and resolution of preexisting target joints [Time frame: During the 52 weeks after stable FIX expression (months 7 to 18 after treatment with CSL222), and then annually during the Posttreatment Follow-up Period (up to 5 years)]
• Number of participants with zero bleeds and zero FIX-treated bleeds [Time frame: During the 52 weeks after stable FIX expression (months 7 to 18 after treatment with CSL222), and during months 7 to: 24, 36, 48, and 60 after treatment with CSL222]
• Percentage of participants with zero bleeds and zero FIX-treated bleeds [Time frame: During the 52 weeks after stable FIX expression (months 7 to 18 after treatment with CSL222), and during months 7 to: 24, 36, 48, and 60 after treatment with CSL222]

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• Center for Inherited Blood Disorders — Orange
• University of Florida — Gainesville
• Arthur M. Blank Hospital - Children's Healthcare of Atlanta — Atlanta
• University of Michigan Medical Center — Ann Arbor
• St. Jude Children's Research Hospital — Memphis

Spain · 2 centers

• Hospital Sant Joan de Déu — Barcelona
• La Paz University Hospital — Madrid

United Kingdom · 2 centers

• St Thomas Hospital — London
• John Radcliffe Hospital - Oxford University Hospitals NHS — Oxford

Austria · 1 center

• Medical University Vienna — Vienna

Belgium · 1 center

• UZ Leuven - Centrum voor Moleculaire en Vasculaire Biologie — Leuven

France · 1 center

• CHU Hopital de la Timone — Marseille

Israel · 1 center

• Chaim Sheba Medical Center — Ramat Gan

Identifiers

NCT: NCT07080905 · CSL222_3004 · 2023-505805-18-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗