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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia B
• Intervention / Treatment: Genetic: AAV5-hFIXco-Padua; Biological: Factor IX (FIX)

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • University Hospital Leuven
• Denmark
  • Copenhagen, Denmark, 2100
    • Righospitalet
• Germany
  • Berlin, Germany, 10249
    • Vivantes Klinikum im Friedrichshain
  • Frankfurt am Main, Germany, 60590
    • Klinikum Der Johann Wolfgang Goethe Universitat
• Ireland
  • Dublin, Ireland, D08 A978
    • National Coagulation Centre, St James's Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC - Locatie AMC
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC
  • Utrecht, Netherlands, 3508 GA
    • UMC Utrecht, Van Creveldkliniek
• Sweden
  • Malmo, Sweden, SE-205 02
    • Center for Thrombosis and Hemostasis Skåne University Hospital Malmö
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • The Cambridge Haemophilia and Thrombophilia Centre Camridge University Hospitals NHS Foundation Trust - Box 217 Addenbrooke's Hospital
  • London, United Kingdom, E1 2ES
    • The Royal London Hospital (Barts Health NHS Trust)
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Los Angeles, California, United States, 90007
      • Los Angeles Orthopedic Hospital
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • San Diego, California, United States, 92161
      • University of California, San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center Hematology and Oncology
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • Buffalo, New York, United States, 14209
      • Hemophilia Center of Western New York
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina, Chapel Hill
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee Health Science Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center & Medical School
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98101
      • Washington Institute for Coagulation
    • Seattle, Washington, United States, 98104
      • Bloodworks Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleeding Rate (ABR) for All Bleeding Episodes	Adjusted ABR for Lead-in and Post-Treatment period was estimated from a repeated measures generalized estimating equations negative binomial regression model accounting for the paired design of the trial with an offset parameter to account for the differential collection periods. Treatment period was included as a categorical covariate.	Lead-in period and months 7-18 post-treatment of AMT-061 (CSL222)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events		Up to 5 years
Factor IX Activity Levels After AMT-061 (CSL222) Dosing	One-stage activated partial thromboplastin time (aPTT) based endogenous FIX activity levels from central laboratory assay.	At Baseline, 6, 12, and 18 months after AMT-061 (CSL222) dosing
Annualized Exogenous FIX Consumption	Annualized consumption of FIX replacement therapy.	Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 (CSL222) dosing
Adjusted Annualized Infusion Rate of FIX Replacement Therapy		Lead-in period and months 7-18 after AMT-061 (CSL222) dosing
Percent of Participants Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 (CSL222) Dosing		Months 7-18 after AMT-061 (CSL222) dosing
Percentage of Participants With Trough FIX Activity <12% of Normal		Lead-in and 3, 12, and 18 months after AMT-061 (CSL222) dosing
ABR for FIX-treated Bleeding Episodes	Adjusted ABR for Lead-In and Post-Treatment period was estimated from a repeated measures generalized estimating equations negative binomial regression model accounting for the paired design of the trial with an offset parameter to account for the differential collection periods. Treatment period was included as a categorical covariate.	Lead-in and Months 7-18 after AMT-061 (CSL222) dosing
Annualized Rate of Spontaneous Bleeding Episodes	Adjusted ABR for Lead-In and Post-Treatment period was estimated from a repeated measures generalized estimating equations negative binomial regression model accounting for the paired design of the trial with an offset parameter to account for the differential collection periods. Treatment period was included as a categorical covariate.	Lead-in period and months 7-18 after AMT-061 (CSL222) dosing
Annualized Rate of Joint Bleeding Episodes	Adjusted ABR for Lead-In and Post-Treatment period was estimated from a repeated measures generalized estimating equations negative binomial regression model accounting for the paired design of the trial with an offset parameter to account for the differential collection periods. Treatment period was included as a categorical covariate.	Lead-in period and months 7-18 after AMT-061 (CSL222) dosing
Mean FIX Activity (%) in Participants With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 (CSL222) Dosing	One-stage aPTT-based endogenous FIX activity levels from central laboratory assay.	At Baseline, 6, 12, and 18 months after AMT-061 (CSL222) dosing
Mean FIX Activity (%) in Participants Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 (CSL222) Dosing	One-stage aPTT-based endogenous FIX activity levels from central laboratory assay.	At Baseline, 6, 12 and 18 months after AMT-061 (CSL222) 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.	Up to 18 months after AMT-061 (CSL222) dosing
Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 (CSL222) Dosing		Lead-in period and months 7-18 post-treatment of AMT-061 (CSL222)
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 the activity was undertaken. A higher score is considered to be more favorable.	Lead-in period and up to 12 months after AMT-061 (CSL222) dosing
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 (CSL222) dosing
Number of Participants With Change (Shift) in Abdominal Ultrasound Results From Normal, Abnormal and Missing to Abnormal Post Treatment	To monitor participants for liver fibrosis and potential occurrences of liver malignancies, abdominal ultrasounds were performed. Number of participants with change in abdominal ultrasound result from normal to abnormal, abnormal to abnormal (no change) and missing to abnormal are reported for this outcome measure.	Up to 5 years
Number of Participants With Anti-AAV5 Antibodies	Number of participants who developed antibodies directed against AAV5 (including IgM, IgG and neutralizing antibodies) are reported for this outcome measure. A participant was reported as having an IgG and IgM anti-AAV5 antibody titer greater than or equal to (≥) the LOD if both the screening and confirmatory test results were positive and the titer value was ≥ 50.	At Month 60
Number of Participants With AAV5 Capsid-specific T Cells		At Month 12 after treatment
Number of Participants With Anti-FIX Antibodies		At Month 60
Number of Participants With FIX Inhibitors and Recovery	Number of participants with >LOD level of fix inhibitors up to Month 60 are reported for this outcome measure. Here, LOD = 0.415 Nijmegen-Bethesda Units per milliliter (NBU/mL).	Up to Month 60
Number of Participants With Increased Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) Levels And Who Used Any Corticosteroids For Treatments	Number of participants with increased AST and ALT levels and who used corticosteroids to treat these elevations are reported for this outcome measure.	Up to Month 60
Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Laboratory Values	Only parameters with post-baseline, newly occurring or worsening potentially clinically significant laboratory values are reported for this outcome measure. Criteria threshold: Hemoglobin: < 80 grams per liter (g/L); Platelet Count: < 50 10^9 cells per liter; AST and ALT: > 2 x Baseline value; Total Bilirubin: > 2 x upper limit of normal (ULN).	Up to Month 60
Number of Participants With Vector DNA Shedding	A participant was considered to no longer be shedding vector DNA if they had a negative laboratory result (<LOD) for 3 or more consecutive timepoints.	Up to 12 months after treatment
Number of Participants With Inflammatory Markers	Inflammatory markers assessed included Interleukin-1beta (IL-1β), Interleukin-2 (IL-2), Interleukin-6 (IL-6), Interferon gamma (IFNγ), and Monocyte chemotactic protein-1 (MCP-1). Lower limit of quantification (LLOQ): IFNγ = 2.86 nanograms per milliliter (ng/mL), IL-1β = 0.60 ng/mL, IL-2 = 0.72 ng/mL, IL-6 = 0.94 ng/mL, MCP-1 = 1.68 ng/mL. Number of participants with inflammatory markers >= LLOQ are reported for this outcome measure.	Up to 12 months after treatment
Number of Participants With Alpha-fetoprotein (AFP) Levels Above LLOQ at Month 60	Number of participants with AFP levels >= LLOQ at Month 60 are reported for this outcome measure. LLOQ for AFP = 1.09 IU/mL.	At Month 60

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Principal Investigator: Steven Pipe, MD, University of Michigan

Publications and helpful links

General Publications

• Pipe SW, Miesbach W, Recht M, Leebeek FWG, Key NS, Castaman G, Lattimore S, Coppens M, Le Quellec S, Mahajan V, Gill S, Drelich D, Monahan PE; HOPE-B Study Group Investigators. Final Analysis of a Study of Etranacogene Dezaparvovec for Hemophilia B. N Engl J Med. 2026 Jan 29;394(5):463-474. doi: 10.1056/NEJMoa2514332. Epub 2025 Dec 7.
• O'Connell N, van der Valk P, Le Quellec S, Gomez E, Monahan PE, Crary SE, Coppens M, Lemons R, Castaman G, Klamroth R, Symington E, Quon DV, Kampmann P. Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B. J Thromb Haemost. 2025 Jan;23(1):73-84. doi: 10.1016/j.jtha.2024.08.027. Epub 2024 Sep 26.
• Coppens M, Pipe SW, Miesbach W, Astermark J, Recht M, van der Valk P, Ewenstein B, Pinachyan K, Galante N, Le Quellec S, Monahan PE, Leebeek FWG; HOPE-B Investigators. Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial. Lancet Haematol. 2024 Apr;11(4):e265-e275. doi: 10.1016/S2352-3026(24)00006-1. Epub 2024 Mar 1.
• Pipe SW, Leebeek FWG, Recht M, Key NS, Castaman G, Miesbach W, Lattimore S, Peerlinck K, Van der Valk P, Coppens M, Kampmann P, Meijer K, O'Connell N, Pasi KJ, Hart DP, Kazmi R, Astermark J, Hermans CRJR, Klamroth R, Lemons R, Visweshwar N, von Drygalski A, Young G, Crary SE, Escobar M, Gomez E, Kruse-Jarres R, Quon DV, Symington E, Wang M, Wheeler AP, Gut R, Liu YP, Dolmetsch RE, Cooper DL, Li Y, Goldstein B, Monahan PE. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. N Engl J Med. 2023 Feb 23;388(8):706-718. doi: 10.1056/NEJMoa2211644.

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2018
• Primary Completion (Actual): September 22, 2021
• Study Completion (Actual): March 19, 2025

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Bleeding; Gene therapy; hemophilia; FIX; factor IX; Viral vector; Padua; AAV (adeno-associated virus); serotype 5 AAV (adeno-associated virus); serotype 5
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hemophilia A; Hemorrhage; Hemophilia B; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Enzymes and Coenzymes; Blood Proteins; Blood Coagulation Factors; Enzyme Precursors; Protein Precursors; Factor IX
• Other Study ID Numbers: CSL222_3001 (CT-AMT-061-02); CT-AMT-061-02 (Other Identifier: Other Study ID Number); 2017-004305-40 (EudraCT Number); 2024-510738-42-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No