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HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients

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: NCT03569891
Recruitment Status : Active, not recruiting
First Posted : June 26, 2018
Results First Posted : October 10, 2022
Last Update Posted : March 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, multi-center, multinational trial to demonstrate the efficacy of AMT-061 and to further describe its safety profile.

The study drug is identified as AAV5-hFIXco-Padua (AMT- 061). 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 pharmaceutical form of AMT-061 is a solution for intravenous infusion administered at a dose of 2 x 10^13 gc/kg.


Condition or disease Intervention/treatment Phase
Hemophilia B Genetic: AAV5-hFIXco-Padua Biological: Factor IX (FIX) Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The reference therapy is prophylactic factor IX replacement therapy used during the lead-in phase prior to treatment with AAV5-hFIXco-Padua (AMT-061).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III, Open-label, Single-dose, Multi-center, Multinational Trial Investigating a 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 : June 27, 2018
Actual Primary Completion Date : September 22, 2021
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: AMT-061

Single infusion of AMT-061

Subjects will receive a single infusion of AAV5-hFIXco-Padua (AMT- 061) at baseline. After study drug administration (post study drug), subjects will be monitored for tolerance to the study drug and detection of potential immediate AEs at the clinical trial site for a few hours after dosing.

 Genetic: AAV5-hFIXco-Padua
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
Other Names:
  • AMT-061
  • etranacogene dezaparvovec
Active Comparator: FIX replacement (Lead-in Period)
During the lead-in phase, which lasted for a minimum of 26 weeks (i.e., ≥6 months), subjects recorded their use of FIX replacement therapy and bleeding episodes in their dedicated e-diary.
 Biological: Factor IX (FIX)
During the lead-in phase, which lasted for a minimum of 26 weeks (i.e., ≥6 months), subjects recorded their use of FIX replacement therapy and bleeding episodes in their dedicated e-diary.


Outcome Measures
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Primary Outcome Measures :
  1. Annualized Bleeding Rate (ABR) for All Bleeding Episodes [ Time Frame: Lead-in period and months 7-18 post-treatment of AMT-061 ]
    ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.


Secondary Outcome Measures :
  1. Factor IX Activity Levels After AMT-061 Dosing [ Time Frame: Baseline and 6,12, and 18 months after AMT-061 dosing ]
  2. Annualized Exogenous Factor IX Consumption [ Time Frame: Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing ]
  3. Adjusted Annualized Infusion Rate of FIX Replacement Therapy [ Time Frame: Lead-in period and months 7-18 after AMT-061 dosing ]
  4. Percent of Subjects Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 Dosing [ Time Frame: Months 7-18 after AMT-061 dosing ]
  5. Percentage of Subjects With Trough FIX Activity <12% of Normal [ Time Frame: Lead-in and 3, 12, and 18 months after AMT-061 dosing ]
  6. ABR for FIX-treated Bleeding Episodes [ Time Frame: Lead-in and Months 7-18 after AMT-061 dosing ]
  7. Number of Spontaneous Bleeding Episodes [ Time Frame: Lead-in period and months 7-18 after AMT-061 dosing ]
  8. Number of Joint Bleeding Episodes [ Time Frame: Lead-in period and months 7-18 after AMT-061 dosing ]
  9. Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing [ Time Frame: Baseline and 6,12, and 18 months after AMT-061 dosing ]
  10. Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing [ Time Frame: Baseline and 6,12, and 18 months after AMT-061 dosing ]
  11. Number of New Target Joints and the Number of New Target Joints Resolved. [ Time Frame: Up to 18 months after AT-061 dosing ]
    A target joint was defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period prior to the dosing visit and which was not resolved by the time of dosing. An identified target joint with ≤2 spontaneous bleeding episodes within a consecutive 12-month period was considered resolved.

  12. Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing [ Time Frame: Lead-in period and months 7-18 post-treatment of AMT-061 ]
  13. International Physical Activity Questionnaire (iPAQ) Overall Score [ Time Frame: Lead-in period and up to 12 months after AT-01 dosing ]
    The iPAQ was designed to provide an evaluation of daily physical activities in metabolic equivalent of task (MET) minutes/week. To calculate MET minutes a week multiply the MET value given (walking = 3.3, moderate activity = 4, vigorous activity = 8) by the minutes the activity was carried out and again by the number of days that that activity was undertaken. A higher score is considered to be more favorable.

  14. EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score [ Time Frame: Lead-in period and up to 12 months after AMT-061 dosing ]
    The EQ-5D-5L descriptive system of health-related QoL states consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). The EQ-5D-5L VAS overall score ranges from 0 to 100. A higher score is considered to be more favorable.

  15. Number of Adverse Events [ Time Frame: 5 years ]
    Follow up and assess any adverse events reported for safety


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
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, and are currently on factor IX prophylaxis
  4. >150 previous exposure days of treatment with factor IX protein

Exclusion Criteria:

  1. History of factor IX inhibitors
  2. Positive factor IX inhibitor test at screening
  3. Select screening laboratory value >2 times upper limit of normal
  4. Positive human immunodeficiency virus (HIV) test 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 at the end of the lead-in phase
  7. Previous gene therapy treatment
  8. Receipt of an experimental agent within 60 days prior to screening
  9. Current participation or anticipated participation within one year after study drug administration in this trial in any other interventional clinical trial involving drugs or devices
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): NCT03569891


Locations
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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 7, 2022
Statistical Analysis Plan  [PDF] June 10, 2021

More Information
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT03569891    
Other Study ID Numbers: CSL222_3001 (CT-AMT-061-02)
First Posted: June 26, 2018    Key Record Dates
Results First Posted: October 10, 2022
Last Update Posted: March 6, 2023
Last Verified: March 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
Keywords provided by CSL Behring:
Gene therapy
FIX
factor IX
Bleeding
Viral vector
 Padua
hemophilia
AAV (adeno-associated virus)
serotype 5 AAV (adeno-associated virus)
serotype 5
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