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

Phase 3RecruitingNCT07080905

CSL Behring20 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemophilia B

Interventions

CSL222 (Adeno-associated viral vector serotype 5 [AAV5]-hFIXco-Padua)GENETIC

Administered as a single IV infusion.

Eligibility

Sex: MALEMin age: 138 MonthsMax age: 206 Months

Medical Language ↔ Plain English

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).

Locations (14)

Center for Inherited Blood Disorders

Orange, California, United States

RECRUITING

University of Florida

Gainesville, Florida, United States

Outcomes

Primary Outcomes

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 Outcomes

Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) total score and change from baseline

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.

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

Mean annualized consumption (IU/year) of FIX replacement therapy (excluding FIX replacement for invasive procedures).

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

Mean annualized infusion rate (infusions/year) of FIX replacement therapy (excluding FIX replacement for invasive procedures).

Central Contacts

Trial Registration Coordinator

CONTACT

1-610-878-4697 clinicaltrials@cslbehring.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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

Queensland Children's Hospital

Brisbane, Australia

RECRUITING

Medical University Vienna

Vienna, Austria

RECRUITING

UZ Leuven - Centrum voor Moleculaire en Vasculaire Biologie

Leuven, Belgium

RECRUITING

CHU Hopital de la Timone

Marseille, France

RECRUITING

Chaim Sheba Medical Center

Ramat Gan, Israel

RECRUITING

...and 4 more locations

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

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

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.

Time frame: At baseline, during the Lead-In Period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years)

Change in the EQ-5D-5L Index Scores

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.

Time frame: At baseline, during the Lead-In Period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years)

Change in the Patient-Reported Outcomes Measurement Information System (PROMIS)-25 total score

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).

Time frame: At baseline, during the Lead-In Period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years)

Change from baseline in PROMIS-29 total score

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).

Time frame: At baseline, during the Lead-In Period (at least 6 months), and in the Posttreatment Follow-up Period (up to 5 years)

Number of participants with endogenous FIX activity of ≥ 5%

Time frame: Up to 5 years after treatment with CSL222

Percentage of participants with endogenous FIX activity of ≥ 5%

Time frame: Up to 5 years after treatment with CSL222

Adverse events - number of participants

Time frame: 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

Time frame: 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

Time frame: During the Lead-in Period (at least 6 months) and during the Posttreatment Follow-up Period (up to 5 years).

Change in liver ultrasound

Time frame: At baseline, month 12 and every 6 months thereafter up to 5 years after CSL222 treatment

Number of participants with antibodies against AAV5

Time frame: From treatment with CSL222 through end of study (up to 5 years after treatment with CSL222)

Number of participants who develop FIX inhibitors

Time frame: 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

Time frame: At baseline and up to 5 years after treatment with CSL222

Number of participants with clinically significant ALT/AST levels

Time frame: At baseline and up to 5 years after treatment with CSL222

Percentage of participants with clinically significant ALT/AST levels

Time frame: At baseline and up to 5 years after treatment with CSL222

Number of participants using corticosteroid for change in AST/ALT levels

Time frame: Up to 5 years after treatment with CSL222

Duration of corticosteroid use for change in AST/ALT levels

Time frame: Up to 5 years after treatment with CSL222

Mean inflammatory markers values

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).

Time frame: Up to 5 years after treatment with CSL222

Change from baseline in Inflammatory markers

Inflammatory markers include IL -1-beta, IL-2, IL-6, interferon-gamma, and MCP-1

Time frame: At baseline and up to 5 years after treatment with CSL222