Back to resultsHOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients
Primary Purpose
Hemophilia B
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
AAV5-hFIXco-Padua
Factor IX (FIX)
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia B focused on measuring Gene therapy, FIX, factor IX, Bleeding, Viral vector, Padua, hemophilia, AAV (adeno-associated virus), serotype 5 AAV (adeno-associated virus), serotype 5
Eligibility Criteria
Inclusion Criteria:
- Male
- Age ≥18 years
- Subjects with congenital hemophilia B, classified as severe or moderately severe, and are currently on factor IX prophylaxis
- >150 previous exposure days of treatment with factor IX protein
Exclusion Criteria:
- History of factor IX inhibitors
- Positive factor IX inhibitor test at screening
- Select screening laboratory value >2 times upper limit of normal
- Positive human immunodeficiency virus (HIV) test 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 at the end of the lead-in phase
- Previous gene therapy treatment
- Receipt of an experimental agent within 60 days prior to screening
- 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
Sites / Locations
- Phoenix Children's Hospital
- Arkansas Children's Hospital
- Los Angeles Orthopedic Hospital
- Children's Hospital of Los Angeles
- University of California, Davis
- University of California, San Diego
- University of Colorado Denver
- Children's National Medical Center Hematology and Oncology
- University of South Florida
- University of Michigan
- Hemophilia Center of Western New York
- University of North Carolina, Chapel Hill
- Oregon Health & Science University
- University of Tennessee Health Science Center
- Vanderbilt University Medical Center
- University of Texas Health Science Center & Medical School
- University of Utah
- Washington Institute for Coagulation
- Bloodworks Northwest
- Cliniques Universitaires Saint-Luc
- University Hospital Leuven
- Righospitalet
- Vivantes Klinikum im Friedrichshain
- Klinikum der Johann Wolfgang Goethe Universitat
- National Coagulation Centre, St James's Hospital
- Amsterdam UMC - Locatie AMC
- Universitair Medisch Centrum Groningen
- Erasmus MC
- UMC Utrecht, Van Creveldkliniek
- Center for Thrombosis and Hemostasis Skåne University Hospital Malmö
- The Cambridge Haemophilia and Thrombophilia Centre Camridge University Hospitals NHS Foundation Trust - Box 217 Addenbrooke's Hospital
- The Royal London Hospital (Barts Health NHS Trust)
- University Hospital Southampton NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
AMT-061
FIX replacement (Lead-in Period)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Annualized Bleeding Rate (ABR) for All Bleeding Episodes
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
Factor IX Activity Levels After AMT-061 Dosing
Annualized Exogenous Factor IX Consumption
Adjusted Annualized Infusion Rate of FIX Replacement Therapy
Percent of Subjects Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 Dosing
Percentage of Subjects With Trough FIX Activity <12% of Normal
ABR for FIX-treated Bleeding Episodes
Number of Spontaneous Bleeding Episodes
Number of Joint Bleeding Episodes
Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing
Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing
Number of New Target Joints and the Number of New Target Joints Resolved.
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.
Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing
International Physical Activity Questionnaire (iPAQ) Overall Score
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.
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score
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.
Number of Adverse Events
Follow up and assess any adverse events reported for safety
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03569891
Brief Title
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 27, 2018 (Actual)
Primary Completion Date
September 22, 2021 (Actual)
Study Completion Date
March 2025 (Anticipated)
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
Keywords
Gene therapy, FIX, factor IX, Bleeding, Viral vector, Padua, hemophilia, AAV (adeno-associated virus), serotype 5 AAV (adeno-associated virus), serotype 5
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
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)
Allocation
Non-Randomized
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AMT-061
Arm Type
Experimental
Arm Description
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.
Arm Title
FIX replacement (Lead-in Period)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Genetic
Intervention Name(s)
AAV5-hFIXco-Padua
Other Intervention Name(s)
AMT-061, etranacogene dezaparvovec
Intervention Description
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
Intervention Type
Biological
Intervention Name(s)
Factor IX (FIX)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Annualized Bleeding Rate (ABR) for All Bleeding Episodes
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
Lead-in period and months 7-18 post-treatment of AMT-061
Secondary Outcome Measure Information:
Title
Factor IX Activity Levels After AMT-061 Dosing
Time Frame
Baseline and 6,12, and 18 months after AMT-061 dosing
Title
Annualized Exogenous Factor IX Consumption
Time Frame
Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing
Title
Adjusted Annualized Infusion Rate of FIX Replacement Therapy
Time Frame
Lead-in period and months 7-18 after AMT-061 dosing
Title
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
Title
Percentage of Subjects With Trough FIX Activity <12% of Normal
Time Frame
Lead-in and 3, 12, and 18 months after AMT-061 dosing
Title
ABR for FIX-treated Bleeding Episodes
Time Frame
Lead-in and Months 7-18 after AMT-061 dosing
Title
Number of Spontaneous Bleeding Episodes
Time Frame
Lead-in period and months 7-18 after AMT-061 dosing
Title
Number of Joint Bleeding Episodes
Time Frame
Lead-in period and months 7-18 after AMT-061 dosing
Title
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
Title
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
Title
Number of New Target Joints and the Number of New Target Joints Resolved.
Description
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.
Time Frame
Up to 18 months after AT-061 dosing
Title
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
Title
International Physical Activity Questionnaire (iPAQ) Overall Score
Description
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.
Time Frame
Lead-in period and up to 12 months after AT-01 dosing
Title
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score
Description
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.
Time Frame
Lead-in period and up to 12 months after AMT-061 dosing
Title
Number of Adverse Events
Description
Follow up and assess any adverse events reported for safety
Time Frame
5 years
10. Eligibility
Sex
Male
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, and are currently on factor IX prophylaxis
>150 previous exposure days of treatment with factor IX protein
Exclusion Criteria:
History of factor IX inhibitors
Positive factor IX inhibitor test at screening
Select screening laboratory value >2 times upper limit of normal
Positive human immunodeficiency virus (HIV) test 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 at the end of the lead-in phase
Previous gene therapy treatment
Receipt of an experimental agent within 60 days prior to screening
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
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 Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Los Angeles Orthopedic Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007
Country
United States
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
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
92161
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's National Medical Center Hematology and Oncology
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Hemophilia Center of Western New York
City
Buffalo
State/Province
New York
ZIP/Postal Code
14209
Country
United States
Facility Name
University of North Carolina, Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Tennessee Health Science Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Health Science Center & Medical School
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
Washington Institute for Coagulation
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Bloodworks Northwest
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Cliniques Universitaires Saint-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
University Hospital Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Righospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Vivantes Klinikum im Friedrichshain
City
Berlin
ZIP/Postal Code
10249
Country
Germany
Facility Name
Klinikum der Johann Wolfgang Goethe Universitat
City
Frankfurt am main
ZIP/Postal Code
60590
Country
Germany
Facility Name
National Coagulation Centre, St James's Hospital
City
Dublin
ZIP/Postal Code
D08 A978
Country
Ireland
Facility Name
Amsterdam UMC - Locatie AMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
UMC Utrecht, Van Creveldkliniek
City
Utrecht
ZIP/Postal Code
3508 GA
Country
Netherlands
Facility Name
Center for Thrombosis and Hemostasis Skåne University Hospital Malmö
City
Malmö
ZIP/Postal Code
SE-205 02
Country
Sweden
Facility Name
The Cambridge Haemophilia and Thrombophilia Centre Camridge University Hospitals NHS Foundation Trust - Box 217 Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
The Royal London Hospital (Barts Health NHS Trust)
City
London
ZIP/Postal Code
E1 2ES
Country
United Kingdom
Facility Name
University Hospital Southampton NHS Foundation Trust
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients
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