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Dose Confirmation Trial of AAV5-hFIXco-Padua

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ClinicalTrials.gov Identifier: NCT03489291
Recruitment Status : Active, not recruiting
First Posted : April 5, 2018
Results First Posted : June 16, 2022
Last Update Posted : June 16, 2022
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE March 19, 2018
First Posted Date  ICMJE April 5, 2018
Results First Submitted Date  ICMJE May 17, 2022
Results First Posted Date  ICMJE June 16, 2022
Last Update Posted Date June 16, 2022
Actual Study Start Date  ICMJE July 24, 2018
Actual Primary Completion Date October 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2022)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 3, 2018)
FIX activity levels [ Time Frame: 6 weeks ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2022)
  • 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.
  • 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.
  • FIX Activity Levels [ Time Frame: 52 weeks post-dose ]
    Measured by the one-stage (aPTT-based) assay.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2018)
  • Usage of FIX replacement therapy [ Time Frame: 52 weeks post-dose ]
    Patients will record all use of prophylactic and on-demand FIX replacement therapy in an e-diary, including reason for FIX use, date and time of infusion and total dose.
  • Annualized Bleeding Rate [ Time Frame: 52 weeks post-dose ]
  • Adverse Events [ Time Frame: 5 years post dose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Confirmation Trial of AAV5-hFIXco-Padua
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Hemophilia B
Intervention  ICMJE Genetic: AAV5-hFIXco-Padua (AMT-061)
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
Study Arms  ICMJE 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).
Intervention: Genetic: AAV5-hFIXco-Padua (AMT-061)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 3, 2018)
3
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 20, 2023
Actual Primary Completion Date October 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
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.
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03489291
Other Study ID Numbers  ICMJE CSL222_2001 (CT-AMT-061-01)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party CSL Behring
Original Responsible Party UniQure Biopharma B.V.
Current Study Sponsor  ICMJE CSL Behring
Original Study Sponsor  ICMJE UniQure Biopharma B.V.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Steven Pipe, MD University of Michigan
PRS Account CSL Behring
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP