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

• 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: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: June 14, 2018
• First Posted Date: June 26, 2018
• Results First Submitted Date: August 15, 2022
• Results First Posted Date: October 10, 2022
• Last Update Posted Date: March 6, 2023
• Actual Study Start Date: June 27, 2018
• Actual Primary Completion Date: September 22, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2022)

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.

Original Primary Outcome Measures (submitted: June 14, 2018)

Factor IX activity levels [ Time Frame: 26 weeks ]

Assessment of Factor IX activity after a single dose of AMT-061

Current Secondary Outcome Measures (submitted: September 26, 2022)

• Factor IX Activity Levels After AMT-061 Dosing [ Time Frame: Baseline and 6,12, and 18 months after AMT-061 dosing ]
• Annualized Exogenous Factor IX Consumption [ Time Frame: Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing ]
• Adjusted Annualized Infusion Rate of FIX Replacement Therapy [ Time Frame: Lead-in period and months 7-18 after AMT-061 dosing ]
• 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 ]
• Percentage of Subjects With Trough FIX Activity <12% of Normal [ Time Frame: Lead-in and 3, 12, and 18 months after AMT-061 dosing ]
• ABR for FIX-treated Bleeding Episodes [ Time Frame: Lead-in and Months 7-18 after AMT-061 dosing ]
• Number of Spontaneous Bleeding Episodes [ Time Frame: Lead-in period and months 7-18 after AMT-061 dosing ]
• Number of Joint Bleeding Episodes [ Time Frame: Lead-in period and months 7-18 after AMT-061 dosing ]
• 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 ]
• 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 ]
• 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.
• 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 ]
• 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.
• 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.
• Number of Adverse Events [ Time Frame: 5 years ]
  Follow up and assess any adverse events reported for safety

Original Secondary Outcome Measures (submitted: June 14, 2018)

• Annualized bleeding rate (ABR) [ Time Frame: 52 weeks ]
  Comparison of ABR between prophylaxis used in the lead-in and after administration of AMT-061
• Use of Factor IX replacement therapy [ Time Frame: 52 weeks ]
  Patients will record all use of prophylactic Factor IX replacement therapy in an e-diary, including reason for Factor IX use, date, and time of infusion and total dose
• Adverse events [ Time Frame: 5 years ]
  Follow up and assess any adverse events reported for safety

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

• Condition: Hemophilia B

Intervention

• Genetic: AAV5-hFIXco-Padua
  Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
  Other Names:

  • AMT-061
  • etranacogene dezaparvovec
• 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.

Study Arms

• 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.

  Intervention: Genetic: AAV5-hFIXco-Padua
• 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.
  Intervention: Biological: Factor IX (FIX)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 15, 2022): 67
• Original Estimated Enrollment (submitted: June 14, 2018): 56
• Estimated Study Completion Date: March 2025
• Actual Primary Completion Date: September 22, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Denmark, Germany, Ireland, Netherlands, Sweden, United Kingdom, United States
• Removed Location Countries: Italy

Administrative Information

• NCT Number: NCT03569891
• Other Study ID Numbers: CSL222_3001 (CT-AMT-061-02)
• 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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: CSL Behring
• Original Responsible Party: UniQure Biopharma B.V.
• Current Study Sponsor: CSL Behring
• Original Study Sponsor: UniQure Biopharma B.V.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Steven Pipe, MD; University of Michigan

• PRS Account: CSL Behring
• Verification Date: March 2023