This is an open-label, single-dose, single-arm, multi-center trial, with a screening, a treatment + post-treatment follow-up phase, and a long-term follow-up phase. The IMP 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 IMP is identified as AAV5-hFIXco-Padua (AMT- 061). The pharmaceutical form of AMT-061 is a solution for intravenous infusion. The administered dose of AMT-061 will be 2 x 10\^13 gc/kg.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
Phoenix Childrens Hospital
Phoenix, Arizona, United States
University of California, Davis
Sacramento, California, United States
University of California, San Diego
San Diego, California, United States
University of Michigan
Ann Arbor, Michigan, United States
Factor IX Activity Levels
To confirm that a single dose of 2x10\^13 gc/kg AMT-061 (CSL222) resulted in factor IX activity levels of ≥5% at 6 weeks after dosing measured by the one-stage (activated partial thromboplastin \[aPTT\]-based) assay.
Time frame: 6 weeks post-dose
Annualized Exogenous Factor IX Usage
Annualized use was calculated as the normalized amount of therapy administered per baseline weight, extrapolated where necessary from any time period less or greater than 1 year. Therapy administered included the total dosage of FIX given as prophylaxis and on-demand. Use for invasive procedures was not included.
Time frame: 52 weeks post-dose
Annualized Bleeding Rate (ABR)
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: 5 years post-dose
Factor IX Activity Levels
Measured by the one-stage (aPTT-based) assay.
Time frame: 52 weeks post-dose
Number of Participants Remaining Free of Continuous Prophylaxis
Participants with no usage of continuous factor IX prophylaxis after AMT-061 (CSL222) treatment were considered free from continuous factor IX prophylaxis use.
Time frame: 1 year post-dose
Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis
The post-continuous-prophylaxis period began on the day after the end of continuous (routine) prophylaxis.Therapy administered included the total dosage of FIX given as prophylaxis and on-demand. Use for invasive procedures was not included.
Time frame: Up to 5 years post-dose
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Number of Participants With Treatment Emergent (TE): Adverse Events (AE), Mild, Moderate, and Severe AEs, AEs Related and Unrelated to the Study Treatment, and Serious AEs
Time frame: Up to 5 years post-dose
Number of Participants With Clinically Meaningful Findings in Hematology and Serum Chemistry Parameters
Clinically meaningful findings were defined as values which were outside the standard normal reference ranges for hematology and serum chemistry parameters.
Time frame: Up to 5 years post-dose
Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Changes in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels
Post-baseline newly occurring or worsening potentially clinically significant ALT and AST levels were defined as values greater than twice the baseline value.
Time frame: From baseline and up to 5 years post-dose
Number of Participants Receiving Corticosteroids for AST and ALT Elevations
Time frame: Up to 5 years post-dose
Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum
Time frame: Baseline and at 5 years post-dose
Number of Participants With AAV5 Capsid-specific T Cell Response
Time frame: Up to Week 52
Number of Participants With Inflammatory Marker Levels Outside Normal Ranges
Inflammatory markers included interleukin (IL)-1β, IL-2, IL-6, interferon gamma (IFNγ), and monocyte chemotactic protein-1 (MCP-1). Only those biomarkers for which the data were higher than the normal range at the specified timepoints have been presented.
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 26, 31, 36, 40, 44, 48 and 52
Time to First Negative Results for Vector Deoxyribonucleic Acid (DNA) From Semen and Blood
Time in weeks until the first negative result confirmed by negative result in 3 consecutive timepoints. A participant was considered to no longer be shedding vector DNA if they had a negative laboratory result for 3 or more consecutive timepoints.
Time frame: Up to 5 years post-dose
Number of Participants With Abnormal Values in Alpha-fetoprotein (AFP) Levels
Participants who were outside the normal limit range were to be reported.
Time frame: Up to 5 years post-dose
Number of Participants With Abnormal Results in Abdominal Ultrasound
Ultrasounds were evaluated by qualified personnel and abnormalities were assessed by the Investigator.
Time frame: At Months 36, 42, 48, 54, and 60 post-dose