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

Not Applicable

Recruiting

• Conditions: Hemophilia B

• Registration Number: NCT07080905
• Lead Sponsor: CSL Behring

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-07-07
• Study First Submitted QC: 2025-07-15
• Study First Posted: 2025-07-23
• Study Start: 2025-07-28
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-04
• Last Update Posted: 2025-08-07
• Primary Completion: 2033-10-24
• Study Completion: 2033-10-24

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

• Assigned male sex at birth
• Aged >=138 months to less than (<) 206 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

• 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 greater than (> 2) × the upper limit of normal (ULN).
  • ALT > 2 × the ULN.
  • AST > 2 x the ULN.
  • 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Annualized Bleeding Rate (ABR)	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

Name	Time	Method
Endogenous FIX activity	At baseline, and at months 6, 12, and 18 after treatment with CSL222
Change from baseline in endogenous FIX activity	At baseline, and at months 6, 12, and 18 after treatment with CSL222
Annualized consumption of FIX replacement therapy	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)	Mean annualized consumption (IU/year) of FIX replacement therapy (excluding FIX replacement for invasive procedures).
Annualized infusion rate of FIX replacement therapy	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)	Mean annualized infusion rate (infusions/year) of FIX replacement therapy (excluding FIX replacement for invasive procedures).
Number of participants remaining free of continuous FIX prophylaxis	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	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	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	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	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	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	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
Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) total score and change from baseline	At baseline, during the Lead-In period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years)	The CHO-KLAT is designed to measure aspects of quality of life for boys with hemophilia. CHO-KLAT is a 35-item questionnaire, with the items categorized into 8 domains (treatment, physical health, family, future, feelings, understanding of hemophilia, other people and friends, and control over your life). The measure is scored on a scale of 0 to 100, with 100 indicating best health-related quality of life.
Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score	At baseline, during the Lead-In Period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years)	The EQ-5D-5L questionnaire visual analogue scale (VAS) measures overall health status on a vertical VAS ranging from 0 to 100. A higher score indicates better quality of life. The change from baseline in the EQ-5D-5L VAS score will be determined.
Change in the EQ-5D-5L Index Scores	At baseline, during the Lead-In Period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years)	The EQ-5D-5L questionnaire descriptive system of health-related quality of life consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) for which responses will be recorded on 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and extreme problems). The responses will be converted into a single index utility score (typically between -0.6 and 1). A higher score indicates better quality of life. The change from baseline in the EQ-5D-5L index score will be determined.
Change in the Patient-Reported Outcomes Measurement Information System (PROMIS)-25 total score	At baseline, during the Lead-In Period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years)	For participants of age 12-16 years. PROMIS-25 is a collection of short forms measuring quality of life in children. It includes domains of physical function mobility, anxiety, depression, fatigue, peer relationships, and pain interference. Each domain consists of 4 questions and are scored from 1 to 5. PROMIS-25 also includes one question on pain intensity that is available as a numeric rating scale and is scored from 0 (no pain) to 10 (worst imaginable pain).
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)	For participants of age \>=17 years. PROMIS-29 version 2.0 is a collection of short forms consisting of 7 PROMIS domains in depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities. Each domain consists of 4 questions and are scored from 1 to 5. PROMIS-29 also includes 1 question on pain intensity that is available as a numeric rating scale and is scored from 0 (no pain) to 10 (worst imaginable pain).
Number of participants with endogenous FIX activity of => 5%	Up to 5 years after treatment with CSL222
Percentage of participants with endogenous FIX activity of => 5%	Up to 5 years after treatment with CSL222
Adverse events - number of participants	During the Lead-in Period (at least 6 months) and during the Posttreatment Follow-up Period (up to 5 years).
Adverse events - percentage of participants	During the Lead-in Period (at least 6 months) and during the Posttreatment Follow-up Period (up to 5 years).
Adverse events - number of events	During the Lead-in Period (at least 6 months) and during the Posttreatment Follow-up Period (up to 5 years).
Change in liver ultrasound	At baseline, month 12 and every 6 months thereafter up to 5 years after CSL222 treatment
Number of participants with antibodies against AAV5	From treatment with CSL222 through end of study (up to 5 years after treatment with CSL222)
Number of participants who develop FIX inhibitors	From treatment with CSL222 through end of study (up to 5 years after treatment with CSL222)
Number of clinically significant clinical laboratory tests (Hematology and Biochemistry) reported as an AE	At baseline and up to 5 years after treatment with CSL222
Number of participants with clinically significant ALT/AST levels	At baseline and up to 5 years after treatment with CSL222
Percentage of participants with clinically significant ALT/AST levels	At baseline and up to 5 years after treatment with CSL222
Number of participants using corticosteroid for change in AST/ALT levels	Up to 5 years after treatment with CSL222
Duration of corticosteroid use for change in AST/ALT levels	Up to 5 years after treatment with CSL222
Mean inflammatory markers values	Up to 5 years after treatment with CSL222	Inflammatory markers include interleukin (IL) -1-beta, IL-2, IL-6, interferon-gamma, and monocyte chemoattractant protein-1 (MCP-1) will be measured and reported as picograms per milliliter (pg/mL).
Change from baseline in Inflammatory markers	At baseline and up to 5 years after treatment with CSL222	Inflammatory markers include IL -1-beta, IL-2, IL-6, interferon-gamma, and MCP-1

Trial Locations

Locations (2)

University of Florida - 84000399; 🇺🇸 Gainesville, Florida, United States

University of Michigan Medical Center - 84000491; 🇺🇸 Ann Arbor, Michigan, United States