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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
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.
Annualized Bleeding Rate (ABR) for All Bleeding Episodes
ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.
Time frame: Lead-in period and months 7-18 post-treatment of AMT-061
Factor IX Activity Levels After AMT-061 Dosing
Time frame: Baseline and 6,12, and 18 months after AMT-061 dosing
Annualized Exogenous Factor IX Consumption
Time frame: Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing
Adjusted Annualized Infusion Rate of FIX Replacement Therapy
Time frame: 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
Time frame: Months 7-18 after AMT-061 dosing
Percentage of Subjects With Trough FIX Activity <12% of Normal
Time frame: Lead-in and 3, 12, and 18 months after AMT-061 dosing
ABR for FIX-treated Bleeding Episodes
Time frame: Lead-in and Months 7-18 after AMT-061 dosing
Number of Spontaneous Bleeding Episodes
Time frame: Lead-in period and months 7-18 after AMT-061 dosing
Number of Joint Bleeding Episodes
Time frame: Lead-in period and months 7-18 after AMT-061 dosing
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Phoenix Children's Hospital
Phoenix, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Los Angeles Orthopedic Hospital
Los Angeles, California, United States
Children's Hospital of Los Angeles
Los Angeles, California, United States
University of California, Davis
Sacramento, California, United States
University of California, San Diego
San Diego, California, United States
University of Colorado Denver
Aurora, Colorado, United States
Children's National Medical Center Hematology and Oncology
Washington D.C., District of Columbia, United States
University of South Florida
Tampa, Florida, United States
University of Michigan
Ann Arbor, Michigan, United States
...and 23 more locations
Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing
Time frame: 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
Time frame: Baseline and 6,12, and 18 months after AMT-061 dosing
Number of New Target Joints and the Number of New Target Joints Resolved.
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.
Time frame: Up to 18 months after AT-061 dosing
Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing
Time frame: Lead-in period and months 7-18 post-treatment of AMT-061
International Physical Activity Questionnaire (iPAQ) Overall Score
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.
Time frame: Lead-in period and up to 12 months after AT-01 dosing
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score
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.
Time frame: Lead-in period and up to 12 months after AMT-061 dosing
Number of Adverse Events
Follow up and assess any adverse events reported for safety
Time frame: 5 years