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

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03569891
• Other study ID #: CSL222_3001 (CT-AMT-061-02)
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 27, 2018
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 67
• Est. completion date: March 2025
• Est. primary completion date: September 22, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

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

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.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	University Hospital Leuven	Leuven
Denmark	Righospitalet	Copenhagen
Germany	Vivantes Klinikum im Friedrichshain	Berlin
Germany	Klinikum der Johann Wolfgang Goethe Universitat	Frankfurt am main
Ireland	National Coagulation Centre, St James's Hospital	Dublin
Netherlands	Amsterdam UMC - Locatie AMC	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Erasmus MC	Rotterdam
Netherlands	UMC Utrecht, Van Creveldkliniek	Utrecht
Sweden	Center for Thrombosis and Hemostasis Skåne University Hospital Malmö	Malmö
United Kingdom	The Cambridge Haemophilia and Thrombophilia Centre Camridge University Hospitals NHS Foundation Trust - Box 217 Addenbrooke's Hospital	Cambridge
United Kingdom	The Royal London Hospital (Barts Health NHS Trust)	London
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Denver	Aurora	Colorado
United States	Hemophilia Center of Western New York	Buffalo	New York
United States	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina
United States	University of Texas Health Science Center & Medical School	Houston	Texas
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Los Angeles Orthopedic Hospital	Los Angeles	California
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	University of California, Davis	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	University of California, San Diego	San Diego	California
United States	Bloodworks Northwest	Seattle	Washington
United States	Washington Institute for Coagulation	Seattle	Washington
United States	University of South Florida	Tampa	Florida
United States	Children's National Medical Center Hematology and Oncology	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  Germany,  Ireland,  Netherlands,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Lead-in period and months 7-18 post-treatment of AMT-061
Secondary	Factor IX Activity Levels After AMT-061 Dosing		Baseline and 6,12, and 18 months after AMT-061 dosing
Secondary	Annualized Exogenous Factor IX Consumption		Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing
Secondary	Adjusted Annualized Infusion Rate of FIX Replacement Therapy		Lead-in period and months 7-18 after AMT-061 dosing
Secondary	Percent of Subjects Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 Dosing		Months 7-18 after AMT-061 dosing
Secondary	Percentage of Subjects With Trough FIX Activity <12% of Normal		Lead-in and 3, 12, and 18 months after AMT-061 dosing
Secondary	ABR for FIX-treated Bleeding Episodes		Lead-in and Months 7-18 after AMT-061 dosing
Secondary	Number of Spontaneous Bleeding Episodes		Lead-in period and months 7-18 after AMT-061 dosing
Secondary	Number of Joint Bleeding Episodes		Lead-in period and months 7-18 after AMT-061 dosing
Secondary	Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing		Baseline and 6,12, and 18 months after AMT-061 dosing
Secondary	Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing		Baseline and 6,12, and 18 months after AMT-061 dosing
Secondary	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.	Up to 18 months after AT-061 dosing
Secondary	Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing		Lead-in period and months 7-18 post-treatment of AMT-061
Secondary	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.	Lead-in period and up to 12 months after AT-01 dosing
Secondary	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.	Lead-in period and up to 12 months after AMT-061 dosing
Secondary	Number of Adverse Events	Follow up and assess any adverse events reported for safety	5 years