Clinical trial NCT03569891: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2018-06-26
Enrollment: 67
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Annualized Bleeding Rate (ABR) for All Bleeding Episodes
timeFrame: Lead-in period and months 7-18 post-treatment of AMT-061
Secondary outcomes:
measure: Factor IX Activity Levels After AMT-061 Dosing
timeFrame: Baseline and 6,12, and 18 months after AMT-061 dosing
measure: Annualized Exogenous Factor IX Consumption
timeFrame: Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing
measure: Adjusted Annualized Infusion Rate of FIX Replacement Therapy
timeFrame: Lead-in period and months 7-18 after AMT-061 dosing
measure: Percent of Subjects Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 Dosing
timeFrame: Months 7-18 after AMT-061 dosing
measure: Percentage of Subjects With Trough FIX Activity <12% of Normal
timeFrame: Lead-in and 3, 12, and 18 months after AMT-061 dosing
measure: ABR for FIX-treated Bleeding Episodes
timeFrame: Lead-in and Months 7-18 after AMT-061 dosing
measure: Number of Spontaneous Bleeding Episodes
timeFrame: Lead-in period and months 7-18 after AMT-061 dosing
measure: Number of Joint Bleeding Episodes
timeFrame: Lead-in period and months 7-18 after AMT-061 dosing
measure: Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing
timeFrame: Baseline and 6,12, and 18 months after AMT-061 dosing
measure: Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing
timeFrame: Baseline and 6,12, and 18 months after AMT-061 dosing
measure: Number of New Target Joints and the Number of New Target Joints Resolved.
timeFrame: Up to 18 months after AT-061 dosing
measure: Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing
timeFrame: Lead-in period and months 7-18 post-treatment of AMT-061
measure: International Physical Activity Questionnaire (iPAQ) Overall Score
timeFrame: Lead-in period and up to 12 months after AT-01 dosing
measure: EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score
timeFrame: Lead-in period and up to 12 months after AMT-061 dosing
measure: Number of Adverse Events
timeFrame: 5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Los Angeles Orthopedic Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center Hematology and Oncology
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Buffalo
country: United States
facility: Hemophilia Center of Western New York
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center & Medical School
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Washington Institute for Coagulation
state: Washington
city: Seattle
country: United States
facility: Bloodworks Northwest
state: Washington
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Copenhagen
country: Denmark
facility: Righospitalet
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Frankfurt am main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe Universitat
city: Dublin
country: Ireland
facility: National Coagulation Centre, St James's Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Locatie AMC
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: UMC Utrecht, Van Creveldkliniek
city: Malmö
country: Sweden
facility: Center for Thrombosis and Hemostasis Skåne University Hospital Malmö
city: Cambridge
country: United Kingdom
facility: The Cambridge Haemophilia and Thrombophilia Centre Camridge University Hospitals NHS Foundation Trust - Box 217 Addenbrooke's Hospital
city: London
country: United Kingdom
facility: The Royal London Hospital (Barts Health NHS Trust)
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: University of Michigan
name: Steven Pipe, MD
role: PRINCIPAL_INVESTIGATOR
References: