HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients
- Conditions
- Hemophilia B
- Interventions
- Genetic: AAV5-hFIXco-PaduaBiological: Factor IX (FIX)
- Registration Number
- NCT03569891
- Lead Sponsor
- CSL Behring
- Brief Summary
This is an open-label, single-dose, multi-center, multinational trial to demonstrate the efficacy of AMT-061 and to further describe its safety profile.
The study drug is identified as AAV5-hFIXco-Padua (AMT- 061). AMT-061 is a recombinant adeno-associated viral vector of serotype 5 (AAV5) containing the Padua variant of a codon-optimized human FIX complementary deoxyribonucleic acid (cDNA) under the control of a liver-specific promoter. The pharmaceutical form of AMT-061 is a solution for intravenous infusion administered at a dose of 2 x 10\^13 gc/kg.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 67
- Male
- Age ≥18 years
- Subjects with congenital hemophilia B, classified as severe or moderately severe, and are currently on factor IX prophylaxis
- >150 previous exposure days of treatment with factor IX protein
- History of factor IX inhibitors
- Positive factor IX inhibitor test at screening
- Select screening laboratory value >2 times upper limit of normal
- Positive human immunodeficiency virus (HIV) test at screening, not controlled with anti-viral therapy
- Active infection with hepatitis B or C virus at screening
- History of Hepatitis B or C exposure, currently controlled by antiviral therapy at the end of the lead-in phase
- Previous gene therapy treatment
- Receipt of an experimental agent within 60 days prior to screening
- Current participation or anticipated participation within one year after study drug administration in this trial in any other interventional clinical trial involving drugs or devices
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description AMT-061 AAV5-hFIXco-Padua Single infusion of AMT-061 Subjects will receive a single infusion of AAV5-hFIXco-Padua (AMT- 061) at baseline. After study drug administration (post study drug), subjects will be monitored for tolerance to the study drug and detection of potential immediate AEs at the clinical trial site for a few hours after dosing. FIX replacement (Lead-in Period) Factor IX (FIX) During the lead-in phase, which lasted for a minimum of 26 weeks (i.e., ≥6 months), subjects recorded their use of FIX replacement therapy and bleeding episodes in their dedicated e-diary.
- Primary Outcome Measures
Name Time Method Annualized Bleeding Rate (ABR) for All Bleeding Episodes Lead-in period and months 7-18 post-treatment of AMT-061 ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.
- Secondary Outcome Measures
Name Time Method Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing Baseline and 6,12, and 18 months after AMT-061 dosing Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing Baseline and 6,12, and 18 months after AMT-061 dosing Annualized Exogenous Factor IX Consumption Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing Percentage of Subjects With Trough FIX Activity <12% of Normal Lead-in and 3, 12, and 18 months after AMT-061 dosing Number of Spontaneous Bleeding Episodes Lead-in period and months 7-18 after AMT-061 dosing Percent of Subjects Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 Dosing Months 7-18 after AMT-061 dosing Factor IX Activity Levels After AMT-061 Dosing Baseline and 6,12, and 18 months after AMT-061 dosing Adjusted Annualized Infusion Rate of FIX Replacement Therapy Lead-in period and months 7-18 after AMT-061 dosing Number of Joint Bleeding Episodes Lead-in period and months 7-18 after AMT-061 dosing ABR for FIX-treated Bleeding Episodes Lead-in and Months 7-18 after AMT-061 dosing Number of New Target Joints and the Number of New Target Joints Resolved. Up to 18 months after AT-061 dosing A target joint was defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period prior to the dosing visit and which was not resolved by the time of dosing. An identified target joint with ≤2 spontaneous bleeding episodes within a consecutive 12-month period was considered resolved.
International Physical Activity Questionnaire (iPAQ) Overall Score Lead-in period and up to 12 months after AT-01 dosing The iPAQ was designed to provide an evaluation of daily physical activities in metabolic equivalent of task (MET) minutes/week. To calculate MET minutes a week multiply the MET value given (walking = 3.3, moderate activity = 4, vigorous activity = 8) by the minutes the activity was carried out and again by the number of days that that activity was undertaken. A higher score is considered to be more favorable.
Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing Lead-in period and months 7-18 post-treatment of AMT-061 Number of Adverse Events 5 years Follow up and assess any adverse events reported for safety
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score Lead-in period and up to 12 months after AMT-061 dosing The EQ-5D-5L descriptive system of health-related QoL states consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). The EQ-5D-5L VAS overall score ranges from 0 to 100. A higher score is considered to be more favorable.
Trial Locations
- Locations (33)
University of Texas Health Science Center & Medical School
🇺🇸Houston, Texas, United States
Bloodworks Northwest
🇺🇸Seattle, Washington, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Los Angeles Orthopedic Hospital
🇺🇸Los Angeles, California, United States
Children's National Medical Center Hematology and Oncology
🇺🇸Washington, District of Columbia, United States
Hemophilia Center of Western New York
🇺🇸Buffalo, New York, United States
University of North Carolina, Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Washington Institute for Coagulation
🇺🇸Seattle, Washington, United States
Righospitalet
🇩🇰Copenhagen, Denmark
Klinikum der Johann Wolfgang Goethe Universitat
🇩🇪Frankfurt am main, Germany
Center for Thrombosis and Hemostasis Skåne University Hospital Malmö
🇸🇪Malmö, Sweden
The Cambridge Haemophilia and Thrombophilia Centre Camridge University Hospitals NHS Foundation Trust - Box 217 Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
The Royal London Hospital (Barts Health NHS Trust)
🇬🇧London, United Kingdom
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom
University of California, San Diego
🇺🇸San Diego, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
University Hospital Leuven
🇧🇪Leuven, Belgium
Erasmus MC
🇳🇱Rotterdam, Netherlands
UMC Utrecht, Van Creveldkliniek
🇳🇱Utrecht, Netherlands
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
University of Tennessee Health Science Center
🇺🇸Memphis, Tennessee, United States
National Coagulation Centre, St James's Hospital
🇮🇪Dublin, Ireland
Amsterdam UMC - Locatie AMC
🇳🇱Amsterdam, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Vivantes Klinikum im Friedrichshain
🇩🇪Berlin, Germany
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
University of South Florida
🇺🇸Tampa, Florida, United States
University of California, Davis
🇺🇸Sacramento, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States