Dose Confirmation Trial of AAV5-hFIXco-Padua

Study Overview
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Brief Summary
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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.

Official Title
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Phase IIb, Open-label, Single-dose, Single-arm, Multi-center Trial to Confirm the Factor IX Activity Level of the Serotype 5 Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene (AAV5-hFIXco-Padua, AMT-061) Administered to Adult Subjects With Severe or Moderately Severe Hemophilia B

Conditions
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Hemophilia B

Intervention / Treatment
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* Genetic: AAV5-hFIXco-Padua (AMT-061)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Age ≥18 years Subjects with congenital hemophilia B classified as severe or moderately severe >20 previous exposure days of treatment with FIX protein Exclusion Criteria: History of FIX inhibitors Positive FIX inhibitor test at screening Select screening laboratory values > 2 times upper normal limit: Positive human immunodeficiency virus (HIV) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open-label, single-dose, single-arm, multi-center trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single infusion of AMT-061<br>Subjects will receive a single infusion of AAV5-hFIXco-Padua (AMT- 061) at baseline. After IMP administration (post IMP), subjects will be monitored for tolerance to the IMP and detection of potential immediate AEs at the clinical trial site for 24 hours (overnight stay). | Genetic: AAV5-hFIXco-Padua (AMT-061)<br>* Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FIX Activity Levels | To confirm that a single dose of 2x10^13 gc/kg AMT-061 will result in FIX activity levels of ≥5% at 6 weeks after dosing measured by the one-stage (aPTT-based) assay. | 6 weeks post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 30 months 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. | 30 months post-dose | 
| FIX Activity Levels | Measured by the one-stage (aPTT-based) assay. | 52 weeks 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. | 30 months post-dose | 
| Safety Endpoints | AEs Hematology and serum chemistry parameters ALT/AST levels and corticosteroid use for ALT/AST elevations Parameters on antibody formation to AAV5 and human factor IX AAV5 capsid-specific T cell response Inflammatory markers Vector DNA in semen and blood AFP | 5 years post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene Therapy, Hemophilia,, Bleeding, Factor IX, FIX, viral vector, Padua