Hemophilia BPhase 3NCT03569891
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients
A Phase 3 study testing AAV5-hFIXco-Padua and Factor IX (FIX) in people with Hemophilia B, run by CSL Behring at 33 sites in 8 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- AAV5-hFIXco-Padua and Factor IX (FIX)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 33 sitesin 8 countries
- Study dates
- 27 Jun 2018to 19 Mar 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
33 sites in 8 countries.
33 sites in 8 countries
United States19 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado Denver
Aurora, Colorado, 80045
Hemophilia Center of Western New York
Buffalo, New York, 14209
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27599
University of Texas Health Science Center & Medical School
Houston, Texas, 77030
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Los Angeles Orthopedic Hospital
Los Angeles, California, 90007
Children's Hospital of Los Angeles
Los Angeles, California, 90027
University of Tennessee Health Science Center
Memphis, Tennessee, 38163
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Oregon Health & Science University
Portland, Oregon, 97239
University of California, Davis
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84108
University of California, San Diego
San Diego, California, 92161
Washington Institute for Coagulation
Seattle, Washington, 98101
Bloodworks Northwest
Seattle, Washington, 98104
University of South Florida
Tampa, Florida, 33612
Children's National Medical Center Hematology and Oncology
Washington D.C., District of Columbia, 20010
Netherlands4 sites
Amsterdam UMC - Locatie AMC
Amsterdam, 1105 AZ
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
Erasmus MC
Rotterdam, 3015 CE
UMC Utrecht, Van Creveldkliniek
Utrecht, 3508 GA
United Kingdom3 sites
The Cambridge Haemophilia and Thrombophilia Centre Camridge University Hospitals NHS Foundation Trust - Box 217 Addenbrooke's Hospital
Cambridge, CB2 0QQ
The Royal London Hospital (Barts Health NHS Trust)
London, E1 2ES
University Hospital Southampton NHS Foundation Trust
Southampton, SO16 6YD
Belgium2 sites
Cliniques Universitaires Saint-Luc
Brussels, 1200
University Hospital Leuven
Leuven, 3000
Germany2 sites
Vivantes Klinikum im Friedrichshain
Berlin, 10249
Klinikum der Johann Wolfgang Goethe Universitat
Frankfurt am Main, 60590
Ireland1 site
National Coagulation Centre, St James's Hospital
Dublin, D08 A978
Sweden1 site
Center for Thrombosis and Hemostasis Skåne University Hospital Malmö
Malmö, SE-205 02
About this study
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
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.
- Conditions
- Hemophilia B
- Being tested
- AAV5-hFIXco-Padua, Factor IX (FIX)
- Keywords
- Gene therapy, FIX, factor IX, Bleeding, Viral vector, Padua, hemophilia, AAV (adeno-associated virus), serotype 5 AAV (adeno-associated virus), serotype 5
- Medical subject headings
- Hemophilia B, Hemorrhage, Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV5-hFIXco-PaduaGenetic
Also called AMT-061, etranacogene dezaparvovec
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
Factor IX (FIX)Biological
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 group | Role | What they receive |
|---|---|---|
| AMT-061 | Experimental | 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. Receives: Genetic: AAV5-hFIXco-Padua |
| FIX replacement (Lead-in Period) | Active comparator | 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. Receives: Biological: Factor IX (FIX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Lead-in period and months 7-18 post-treatment of AMT-061 (CSL222)
Secondary outcomes (25)
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.
Measured: At Baseline, 6, 12, and 18 months after AMT-061 (CSL222) dosing
Annualized Exogenous FIX Consumption
Annualized consumption of FIX replacement therapy.
Measured: 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
Measured: 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
Measured: Months 7-18 after AMT-061 (CSL222) dosing
Percentage of Participants With Trough FIX Activity <12% of Normal
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: Lead-in period and up to 12 months after AMT-061 (CSL222) dosing
Number of Participants With Adverse Events
Measured: Up to 5 years
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.
Measured: 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.
Measured: At Month 60
Number of Participants With AAV5 Capsid-specific T Cells
Measured: At Month 12 after treatment
Number of Participants With Anti-FIX Antibodies
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2018
- Study start27 Jun 2018
- Primary completion22 Sep 2021
- Study completion19 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Steven Pipe, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03569891
- Sponsor's protocol ID
- CSL222_3001 (CT-AMT-061-02)
- Other IDs
- CT-AMT-061-02, 2017-004305-40, 2024-510738-42-00, 2017
- Status last verified
- Feb 2026
- First submitted
- 14 Jun 2018
- Last updated
- 27 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 41358585Parman T, Pizzurro DM, Lucas J, Peng Z. Mutagenesis and Carcinogenesis Risk Evaluation for AAV and Lentiviral Gene Therapies. Int J Toxicol. 2025 May-Jun;44(3):183-195. doi: 10.1177/10915818251318248. Epub 2025 Feb 11.
PubMed 39935281O'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.
PubMed 39341368Coppens 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.
PubMed 38437857Pipe 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.
PubMed 36812434