Dose Confirmation Trial of AAV5-hFIXco-Padua

Hemophilia B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03489291
• Other study ID #: CSL222_2001 (CT-AMT-061-01)
• Status: Completed
• Phase: Phase 2
• Start date: July 24, 2018
• Est. completion date: September 21, 2023

Study information

• Verified date: November 2023
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: September 21, 2023
• Est. primary completion date: October 30, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male

2. Age =18 years

3. Subjects with congenital hemophilia B classified as severe or moderately severe

4. >20 previous exposure days of treatment with FIX protein

Exclusion Criteria:

1. History of FIX inhibitors

2. Positive FIX inhibitor test at screening

3. Select screening laboratory values > 2 times upper normal limit:

4. Positive human immunodeficiency virus (HIV) at screening, not controlled with anti-viral therapy

5. Active infection with Hepatitis B or C virus at screening

6. History of Hepatitis B or C exposure, currently controlled by antiviral therapy

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Genetic:
• AAV5-hFIXco-Padua (AMT-061)
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	University of California, Davis	Sacramento	California
United States	University of California, San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	FIX Activity Levels	Measured by the one-stage (aPTT-based) assay.	52 weeks post-dose
Secondary	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
Secondary	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