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Dose Confirmation Trial of AAV5-hFIXco-Padua

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03489291
Recruitment Status : Active, not recruiting
First Posted : April 5, 2018
Results First Posted : June 16, 2022
Last Update Posted : April 6, 2023
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Description
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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.


Condition or disease Intervention/treatment Phase
Hemophilia B Genetic: AAV5-hFIXco-Padua (AMT-061) Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: open-label, single-dose, single-arm, multi-center trial
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 24, 2018
Actual Primary Completion Date : October 30, 2018
Estimated Study Completion Date : September 20, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Single infusion of AMT-061
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)
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)


Outcome Measures
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Primary Outcome Measures :
  1. FIX Activity Levels [ Time Frame: 6 weeks post-dose ]
    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 :
  1. Annualized Exogenous Factor IX Usage [ Time Frame: 30 months post-dose ]
    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.

  2. Annualized Bleeding Rate (ABR) [ Time Frame: 30 months post-dose ]
    ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.

  3. FIX Activity Levels [ Time Frame: 52 weeks post-dose ]
    Measured by the one-stage (aPTT-based) assay.

  4. Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis [ Time Frame: 30 months post-dose ]
    The Post-Continuous-Prophylaxis period began on the day after the end of continuous (routine) prophylaxis.

  5. Safety Endpoints [ Time Frame: 5 years post-dose ]
    • 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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   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.
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03489291


Locations
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United States, Arizona
Phoenix Childrens Hospital
Phoenix, Arizona, United States, 85016
United States, California
University of California, Davis
Sacramento, California, United States, 95817
University of California, San Diego
San Diego, California, United States, 92122
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
CSL Behring
Investigators
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Principal Investigator: Steven Pipe, MD University of Michigan
  Study Documents (Full-Text)

Documents provided by CSL Behring:
Study Protocol  [PDF] February 8, 2022
Statistical Analysis Plan  [PDF] December 7, 2021

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT03489291    
Other Study ID Numbers: CSL222_2001 (CT-AMT-061-01)
First Posted: April 5, 2018    Key Record Dates
Results First Posted: June 16, 2022
Last Update Posted: April 6, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by CSL Behring:
Hemophilia,
Gene Therapy
Bleeding
Factor IX
 FIX
viral vector
Padua
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
 Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked