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Dose Confirmation Trial of AAV5-hFIXco-Padua

Primary Purpose

Hemophilia B

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AAV5-hFIXco-Padua (AMT-061)
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia B focused on measuring Hemophilia,, Gene Therapy, Bleeding, Factor IX, FIX, viral vector, Padua

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Phoenix Childrens Hospital
  • University of California, Davis
  • University of California, San Diego
  • University of Michigan

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single infusion of AMT-061

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
FIX Activity Levels
Measured by the one-stage (aPTT-based) assay.
Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis
The Post-Continuous-Prophylaxis period began on the day after the end of continuous (routine) prophylaxis.
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

Full Information

First Posted
March 19, 2018
Last Updated
October 9, 2023
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT03489291
Brief Title
Dose Confirmation Trial of AAV5-hFIXco-Padua
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
July 24, 2018 (Actual)
Primary Completion Date
October 30, 2018 (Actual)
Study Completion Date
September 21, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
Keywords
Hemophilia,, Gene Therapy, Bleeding, Factor IX, FIX, viral vector, Padua

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
open-label, single-dose, single-arm, multi-center trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single infusion of AMT-061
Arm Type
Experimental
Arm Description
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).
Intervention Type
Genetic
Intervention Name(s)
AAV5-hFIXco-Padua (AMT-061)
Intervention Description
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
Primary Outcome Measure Information:
Title
FIX Activity Levels
Description
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.
Time Frame
6 weeks post-dose
Secondary Outcome Measure Information:
Title
Annualized Exogenous Factor IX Usage
Description
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
30 months post-dose
Title
Annualized Bleeding Rate (ABR)
Description
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
30 months post-dose
Title
FIX Activity Levels
Description
Measured by the one-stage (aPTT-based) assay.
Time Frame
52 weeks post-dose
Title
Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis
Description
The Post-Continuous-Prophylaxis period began on the day after the end of continuous (routine) prophylaxis.
Time Frame
30 months post-dose
Title
Safety Endpoints
Description
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
Time Frame
5 years post-dose

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Hemophilia B is an X-linked, recessive condition, since it occurs almost exclusively in males. Females typically are asymptomatic carriers. Therefore eligibility is restricted to male participants.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Pipe, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Phoenix Childrens Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
University of California, Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92122
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31698454
Citation
Von Drygalski A, Giermasz A, Castaman G, Key NS, Lattimore S, Leebeek FWG, Miesbach W, Recht M, Long A, Gut R, Sawyer EK, Pipe SW. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv. 2019 Nov 12;3(21):3241-3247. doi: 10.1182/bloodadvances.2019000811. Erratum In: Blood Adv. 2020 Aug 11;4(15):3668.
Results Reference
derived

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Dose Confirmation Trial of AAV5-hFIXco-Padua

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