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)

NCT06003387 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CSL222_30052023-509590-23-00
• Study Type: interventional
• Target: 35
• Locations: 12 countries
• Sites: 26

Brief Summary

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.

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (1)

• 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.

  Months 7 to 18 after CSL222 treatment

Secondary Outcomes (30)

• Number of participants with Treatment Emergent Adverse Events (TEAEs)

  Up to 60 months after CSL222 treatment

• Percentage of participants with TEAEs

  Up to 60 months after CSL222 treatment

• Number of TEAEs

  Up to 60 months after CSL222 treatment

• Change in Liver ultrasound

  Up to 60 months after CSL222 treatment

• Number of participants who develop Factor IX (FIX) Inhibitors

  Up to 60 months after CSL222 treatment

Study Arms (1)

CSL222

EXPERIMENTAL

Participants will receive CSL222 as a single intravenous (IV) infusion of 2 × 10\^13 genome copies per kilogram (gc/kg) on Day 1.

Genetic: CSL222 (AAV5-hFIXco-Padua)

Interventions

CSL222 (AAV5-hFIXco-Padua) GENETIC

Administered as a single IV infusion.

Also known as: Etranacogene dezaparvovec

CSL222

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (26)

University of California, San Diego (UCSD)

San Diego, California, 92121, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

RECRUITING

Royal Brisbane Hospital

Herston, Queensland, 4029, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

McMaster University - Hamilton

Hamilton, Ontario, L8N 3Z5, Canada

RECRUITING

Queen Mary Hospital

Hong Kong, 999077, Hong Kong

RECRUITING

Prince of Wales Hospital Chinese University of Hong Kong

Shatin, 999077, Hong Kong

RECRUITING

Sheba Medical Center

Tel Litwinsky, 5265601, Israel

RECRUITING

Centro de Investigacion Clinica GRAMEL S.C.

Mexico City, Mexico City, 3720, Mexico

RECRUITING

King Faisal Specialist Hospital and Research Center

Riyadh, 11471, Saudi Arabia

RECRUITING

National University Hospital

Singapore, 110974, Singapore

RECRUITING

Singapore General Hospital

Singapore, 169608, Singapore

RECRUITING

Haemophilia Comprehensive Care Centre

Johannesburg, 2193, South Africa

RECRUITING

Kyungpook National University Hospital

Daegu, 41944, South Korea

RECRUITING

Kyung Hee University Hospital at Gangdong

Seoul, 05278, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 3722, South Korea

RECRUITING

Tri-Service General Hospital

Taipei, Neihu District, 114, Taiwan

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)

Kaohsiung City, Sanmin District, 80756, Taiwan

RECRUITING

Changhua Christian Hospital (CCH)

Chang-hua, 500, Taiwan

RECRUITING

Taichung Veterans General Hospital -

Taichung, 40705, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100225, Taiwan

RECRUITING

Ege University Medical Faculty

Bornova, 35100, Turkey (Türkiye)

RECRUITING

Gaziantep University Sahinbey Research and Practice Hospital

Gaziantep, 27310, Turkey (Türkiye)

RECRUITING

Özel Acibadem Adana Hastanesi

Seyhan, 01130, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Study Director

  CSL Behring

  STUDY DIRECTOR

Central Study Contacts

Trial Registration Coordinator

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 22, 2023
• Study Start: January 30, 2024
• Primary Completion (Estimated): October 4, 2028
• Study Completion (Estimated): April 2, 2032
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.
• Access Criteria: Proposed research should seek to answer a previously unanswered important medical or scientific question. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

Locations

ME (1); HK (2); SG (2); AU (4); KR (3); ZA (1); CA (1); US (2); IL (1); SA (1); TW (5); TU (3)