Hemophilia B
Conditions
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.
Interventions
GENETICCSL222 (Adeno-associated viral vector serotype 5 [AAV5]-hFIXco-Padua)
Administered as a single IV infusion.
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
138 Months to 206 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) total score and change from baseline | At baseline and Month 18 post treatment | The CHO-KLAT is designed to measure aspects of quality of life for boys with hemophilia. CHO-KLAT is a 40-item questionnaire, available in both child self-report (for ages 7 to 18) and parent-proxy versions (for ages 4 to 18). Items are categorized into 7 key domains (Activities, Autonomy, Bleeding, Emotional Health, Hemophilia Knowledge, Social Functioning, and Treatment). The measure is scored on a scale of 0 to 100, with 100 indicating best health-related quality of life. |
| 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 | — |
| 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 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 |
Countries
Australia, Austria, Belgium, France, Israel, Spain, United Kingdom, United States
Contacts
CONTACTTrial Registration Coordinator
STUDY_DIRECTORStudy Director
CSL Behring
Outcome results
None listed