Efficacy and Safety of CSL222 (Etranacogene Dezaparvovec) Gene Therapy in Adults With Hemophilia B With Pretreatment Adeno-associated Virus Serotype 5 (AAV5) Neutralizing Antibodies (Nabs)

Phase 3RecruitingNCT06003387

CSL Behring35 enrolled

Overview

The purpose of this study is to assess the risk of bleeding due to failure of expected pharmacological action of CSL222 in adults with severe or moderately severe hemophilia B with detectable pretreatment AAV5 Nabs.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemophilia B

Interventions

CSL222 (AAV5-hFIXco-Padua)GENETIC

Administered as a single IV infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * nd considered legally an adult, as defined by country regulations. * •Has 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 is on continuous routine FIX prophylaxis. * • Has 2 consecutive detectable AAV5 NAb titer results between Screening and Visit L-Final using a validated AAV5 NAb assay (based on central laboratory results). * • Has greater than (\>) 150 previous exposure days to FIX replacement therapy. * • Has been on stable FIX prophylaxis for at least 2 months before Screening. * • Has demonstrated capability to independently, accurately, and in a timely manner complete the eDiary during the Lead-in Period, as judged by the investigator. * • Acceptance to adhere to contraception guidelines. * • Able to provide informed consent after receipt of verbal and written information about the study. * • Investigator believes that the participant (or the participant's legally acceptable representative\[s\]) understands the nature, scope, and possible consequences of the study and is able to adhere to the study procedures. Exclusion Criteria: * • History of FIX inhibitors or positive FIX inhibitor test at Prescreening, Screening or Visit L-Final (based on central laboratory results). * • Screening or Visit L-Final laboratory values (based on central laboratory results) of total bilirubin \> 2 × the upper limit of normal (ULN) (except if caused by Gilbert's syndrome). * • Screening or Visit L-Final laboratory values (based on central laboratory results) of any of the following laboratory abnormalities: * a) ALT \> 2 × the ULN * b) AST \> 2 × the ULN * c) Alkaline phosphatase \> 2 × the ULN * d) Serum creatinine \> 2 × the ULN * e) Hemoglobin less than (\<) 8 g/dL * • Any condition other than hemophilia B resulting in an increased bleeding tendency. * • Thrombocytopenia, defined as a platelet count \<50 × 10\^9/L, at Screening or Visit L Final (based on central laboratory results). * • Any uncontrolled or untreated infection (human immunodeficiency virus \[HIV\], hepatitis B virus \[HBV\] and hepatitis C virus \[HCV\], or any other significant concurrent, uncontrolled medical condition 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. * • Known history of allergy to corticosteroids or known medical condition that would require chronic administration of oral corticosteroids. * • Known uncontrolled allergic conditions or allergy / hypersensitivity to any component of the CSL222 excipients (ie, sucrose, potassium chloride, potassium dihydrogen phosphate, sodium chloride, and disodium hydrogen phosphate). * • Previous AAV5 gene therapy treatment. * • Receipt of an experimental agent or device within 60 days before Screening until the end of the study.

Locations (25)

Outcomes

Primary Outcomes

Annualized Bleeding Rate (ABR)

The total bleeding episodes will be analyzed. ABR is calculated as the total bleeding episodes divided by the total time at risk.

Time frame: Months 7 to 18 after CSL222 treatment

Secondary Outcomes

Number of participants with Treatment Emergent Adverse Events (TEAEs)

Time frame: Up to 60 months after CSL222 treatment

Percentage of participants with TEAEs

Time frame: Up to 60 months after CSL222 treatment

Number of TEAEs

Time frame: Up to 60 months after CSL222 treatment

Change in Liver ultrasound

Time frame: Up to 60 months after CSL222 treatment

Number of participants who develop Factor IX (FIX) Inhibitors

Time frame: Up to 60 months after CSL222 treatment

Percentage of participants who develop FIX Inhibitors

Time frame: Up to 60 months after CSL222 treatment

Change in hematology and biochemistry parameters

Time frame: Up to 60 months after CSL222 treatment

Number of participants with clinically significant increase in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)

Time frame: Up to 60 months after CSL222 treatment

Percentage of participants with clinically significant increase in ALT or AST

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.

University of California, San Diego (UCSD) - 84000460

San Diego, California, United States

RECRUITING

University of Michigan - 84000285

Ann Arbor, Michigan, United States

RECRUITING

Royal Prince Alfred Hospital - 03600044

Camperdown, New South Wales, Australia

RECRUITING

Royal Brisbane Hospital - 03600045

Herston, Queensland, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

RECRUITING

The Alfred Hospital - 03600043

Melbourne, Victoria, Australia

RECRUITING

McMaster University - Hamilton - 12400017

Hamilton, Ontario, Canada

RECRUITING

Queen Mary Hospital - 34400001

Hong Kong, Hong Kong

RECRUITING

Prince of Wales Hospital Chinese University of Hong Kong - 34400002

Shatin, Hong Kong

RECRUITING

Sheba Medical Center - 37600004

Tel Litwinsky, Israel

RECRUITING

...and 15 more locations

Time frame: Up to 60 months after CSL222 treatment

Corticosteroid use for ALT or AST increases after CSL222 treatment

Time frame: Up to 60 months after CSL222 treatment

Number of participants with clinically significant Alpha-fetoprotein (AFP)

Time frame: Baseline and up to 60 months after CSL222 treatment

Percentage of participants with clinically significant AFP

Time frame: Baseline and up to 60 months after CSL222 treatment

Number of participants with infusion related reactions or hypersensitivity reactions

Time frame: Throughout CSL222 infusion period and up to 60 months after CSL222 treatment

Percentage of participants with infusion related reactions or hypersensitivity reactions

Time frame: Throughout CSL222 infusion period and up to 60 months after CSL222 treatment

Change in the Uncontaminated Endogenous FIX activity

Time frame: Baseline and up to Months 6, 12, and 18 after CSL222 treatment

Annualized consumption of FIX replacement therapy

Time frame: Months 7 to 18 after CSL222 treatment

Annualized infusion rate of FIX replacement therapy

Time frame: Months 7 to 18 after CSL222 treatment

Number of participants remaining free of continuous FIX prophylaxis

Time frame: Months 7 to 18 after CSL222 treatment

Percentage of participants remaining free of continuous FIX prophylaxis

Time frame: Months 7 to 18 after CSL222 treatment

ABR for spontaneous bleeding episodes

Time frame: Months 7 to 18 after CSL222 treatment

ABR for joint bleeding episodes

Time frame: Months 7 to 18 after CSL222 treatment

ABR for FIX-treated bleeding episodes

Time frame: Months 7 to 18 after CSL222 treatment

Correlation analysis of FIX activity levels with baseline AAV5 NAb titers

Time frame: Months 7 to 18 after CSL222 treatment

Number of participants with new target joints and resolved pre-existing target joints

Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint.

Time frame: Months 7 to 18 after CSL222 treatment

Number of participants with zero bleeding episodes and zero FIX-treated bleeding episodes

Time frame: Months 7 to 18 after CSL222 treatment

Percentage of participants with zero bleeding episodes and zero FIX-treated bleeding episodes

Time frame: Months 7 to 18 after CSL222 treatment

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: Baseline and up to 18 months after CSL222 treatment

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: Baseline and up to 18 months after CSL222 treatment

Number of Participants with Uncontaminated Endogenous FIX Activity of Greater than or Equal to (>=) 5%

Time frame: Months 7 to 18 after CSL222 treatment

Percentage of Participants with Uncontaminated Endogenous FIX Activity of >= 5%

Time frame: Months 7 to 18 after CSL222 treatment