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

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

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.

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.

2025-12-071 citations

10.1056/nejmoa2514332

End-of-study analysis of the HOPE-B trial confirms the durable efficacy and safety of etranacogene dezaparvovec hemophilia b gene therapy over 5 years

Steven W. Pipe, Wolfgang Miesbach, Michael Recht, Frank W.G. Leebeek, Nigel S. Key et al. (13 authors)

Blood2025-11-03

10.1182/blood-2025-538

Elevation of liver health biomarkers before and after etranacogene dezaparvovec gene therapy in hemophilia B: Associations with long-term clinical outcomes

Wolfgang Miesbach, Steven W. Pipe, Cédric Hermans, Michael Recht, Miguel A. Escobar et al. (10 authors)

Blood2025-11-03

10.1182/blood-2025-6093

Development of an Agent-Based Model to Investigate Response Durability in Hemophilia B Patients Treated with the AAV-Based Coagulation Factor IX (FIX) Gene Therapy Etranacogene Dezaparvovec

Yuezhe Li, Partha Nandy, Eric Jordie, Karsten Peppel, Timothy D. Knab et al. (8 authors)

Blood2024-11-05

10.1182/blood-2024-204833

Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B.

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.

2024-09-263 citations

10.1016/j.jtha.2024.08.027

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.

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.

2024-03-0132 citations

10.1016/s2352-3026(24)00006-1

Etranacogene Dezaparvovec Shows Sustained Efficacy and Safety in Adult Patients With Severe or Moderately Severe Haemophilia B 3 Years After Administration in the HOPE-B Trial

Steven W. Pipe, Paul van der Valk, Peter Verhamme, Peter Kampmann, Frank W.G. Leebeek et al. (21 authors)

Hämostaseologie2024-02-011 citations

10.1055/s-0044-1779108

HIV Comorbid Infection and Etranacogene Dezaparvovec Therapy: Efficacy and Safety Results From Phase 2b and Pivotal Phase 3 HOPE-B Trials 3 Years after Administration

Steven W. Pipe, Esteban Moreno Gómez, Cédric Hermans, Adam Giermasz, Peter Kampmann et al. (9 authors)

Hämostaseologie2024-02-01

10.1055/s-0044-1779148

Long-Term Bleeding Protection, Sustained FIX Activity, Reduction of FIX Consumption and Safety of Hemophilia B Gene Therapy: Results from the HOPE-B Trial 3 Years after Administration of a Single Dose of Etranacogene Dezaparvovec in Adult Patients with Severe or Moderately Severe Hemophilia B

Steven W. Pipe, Paul van der Valk, Peter Verhamme, Peter Kampmann, Frank W.G. Leebeek et al. (21 authors)

Blood2023-11-0213 citations

10.1182/blood-2023-187624

HIV Comorbid Infection and Liver-Directed AAV-Based Gene Therapy in Adults with Severe and Moderately Severe Hemophilia B: Efficacy and Safety Results from Phase 2b and the Pivotal Phase 3 HOPE-B Trials 3 Years after Administration of a Single Dose of Etranacogene Dezaparvovec

Steven W. Pipe, Esteban Moreno Gómez, Cédric Hermans, Adam Giermasz, Peter Kampmann et al. (9 authors)

Blood2023-11-02

10.1182/blood-2023-187059

Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B

Steven W. Pipe, Frank W.G. Leebeek, Michael Recht, Nigel S. Key, Giancarlo Castaman et al. (38 authors)

New England Journal of Medicine2023-02-22303 citations

10.1056/nejmoa2211644

Adults with severe or moderately severe haemophilia B receiving etranacogene dezaparvovec in the HOPE-B phase 3 trial experience a stable increase in mean Factor IX activity levels and durable haemostatic protection after 24 months’ follow-up

W S Pipe, WG F Leebeek, Michael Recht, S N Key, Susan Lattimore et al. (15 authors)

Hämostaseologie2023-02-011 citations

10.1055/s-0042-1760523

Durability of bleeding protection and Factor IX activity in individuals with and without adeno-associated virus serotype 5 neutralising antibodies (Titres <1:700) in the phase 3 HOPE-B trial of etranacogene dezaparvovec gene therapy for haemophilia B

W S Pipe, WG F Leebeek, Michael Recht, S N Key, Susan Lattimore et al. (13 authors)

Hämostaseologie2023-02-01

10.1055/s-0042-1760524

Adults with Severe or Moderately Severe Hemophilia B Receiving Etranacogene Dezaparvovec in the HOPE-B Phase 3 Clinical Trial Continue to Experience a Stable Increase in Mean Factor IX Activity Levels and Durable Hemostatic Protection after 24 Months’ Follow-up

Steven W. Pipe, Frank W.G. Leebeek, Michael Recht, Nigel S. Key, Susan Lattimore et al. (15 authors)

Blood2022-11-1511 citations

10.1182/blood-2022-166135

Durability of Bleeding Protection and Factor IX Activity Levels Are Demonstrated in Individuals with and without Adeno-Associated Virus Serotype 5 Neutralizing Antibodies (Titers &lt;1:700) with Comparable Safety in the Phase 3 HOPE-B Clinical Trial of Etranacogene Dezaparvovec Gene Therapy for Hemophilia B

Steven W. Pipe, Frank W.G. Leebeek, Michael Recht, Nigel S. Key, Susan Lattimore et al. (13 authors)

Blood2022-11-154 citations

10.1182/blood-2022-166745

Durability of Factor IX Activity and Bleeding Rate in People with Severe or Moderately Severe Hemophilia B after 5 Years of Follow-up in the Phase 1/2 Study of AMT-060, and after 3 Years of Follow-up in the Phase 2b and 2 Years of Follow-up in the Phase 3 Studies of Etranacogene Dezaparvovec (AMT-061)

Wolfgang Miesbach, Michael Recht, Nigel S. Key, Krupa Sivamurthy, Paul E. Monahan et al. (6 authors)

Blood2022-11-152 citations

10.1182/blood-2022-166810

Comprehensive analysis and prediction of long-term durability of factor IX activity following etranacogene dezaparvovec gene therapy in the treatment of hemophilia B.

Shah J, Kim H, Sivamurthy K, Monahan PE, Fries M.

2022-10-2522 citations

10.1080/03007995.2022.2133492

First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies

Steven W. Pipe, Michael Recht, Nigel S. Key, Frank W.G. Leebeek, Giancarlo Castaman et al. (36 authors)

Blood2020-11-1916 citations

10.1182/blood-2020-143560

Prevalence and Relevance of Pre-Existing Anti-Adeno-Associated Virus Immunity in the Context of Gene Therapy for Crigler–Najjar Syndrome

Sem J. Aronson, P. Véron, Fanny Collaud, Aurélie Hubert, Virginie Delahais et al. (17 authors)

Human Gene Therapy2019-09-1060 citations

10.1089/hum.2019.143

Interventions

GENETICAAV5-hFIXco-Padua

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

BIOLOGICALFactor 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 design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

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).

Eligibility

Sex/Gender

MALE

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Annualized Bleeding Rate (ABR) for All Bleeding Episodes	Lead-in period and months 7-18 post-treatment of AMT-061 (CSL222)	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.

Secondary

Measure	Time frame	Description
Factor IX Activity Levels After AMT-061 (CSL222) Dosing	At Baseline, 6, 12, and 18 months after AMT-061 (CSL222) dosing	One-stage activated partial thromboplastin time (aPTT) based endogenous FIX activity levels from central laboratory assay.
Annualized Exogenous FIX Consumption	Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 (CSL222) dosing	Annualized consumption of FIX replacement therapy.
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	Lead-in and Months 7-18 after AMT-061 (CSL222) dosing	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.
Annualized Rate of Spontaneous Bleeding Episodes	Lead-in period and months 7-18 after AMT-061 (CSL222) dosing	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.
Annualized Rate of Joint Bleeding Episodes	Lead-in period and months 7-18 after AMT-061 (CSL222) dosing	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.
Mean FIX Activity (%) in Participants With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 (CSL222) Dosing	At Baseline, 6, 12, and 18 months after AMT-061 (CSL222) dosing	One-stage aPTT-based endogenous FIX activity levels from central laboratory assay.
Mean FIX Activity (%) in Participants Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 (CSL222) Dosing	At Baseline, 6, 12 and 18 months after AMT-061 (CSL222) dosing	One-stage aPTT-based endogenous FIX activity levels from central laboratory assay.
Number of New Target Joints and the Number of New Target Joints Resolved	Up to 18 months after AMT-061 (CSL222) 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 (CSL222) Dosing	Lead-in period and months 7-18 post-treatment of AMT-061 (CSL222)	—
International Physical Activity Questionnaire (iPAQ) Overall Score	Lead-in period and up to 12 months after AMT-061 (CSL222) 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 the activity was undertaken. A higher score is considered to be more favorable.
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score	Lead-in period and up to 12 months after AMT-061 (CSL222) 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 Participants With Adverse Events	Up to 5 years	—
Number of Participants With Change (Shift) in Abdominal Ultrasound Results From Normal, Abnormal and Missing to Abnormal Post Treatment	Up to 5 years	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.
Number of Participants With Anti-AAV5 Antibodies	At Month 60	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.
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	Up to Month 60	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).
Number of Participants With Increased Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) Levels And Who Used Any Corticosteroids For Treatments	Up to Month 60	Number of participants with increased AST and ALT levels and who used corticosteroids to treat these elevations are reported for this outcome measure.
Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Laboratory Values	Up to Month 60	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).
Number of Participants With Vector DNA Shedding	Up to 12 months after treatment	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.
Number of Participants With Inflammatory Markers	Up to 12 months after treatment	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.
Number of Participants With Alpha-fetoprotein (AFP) Levels Above LLOQ at Month 60	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.

Countries

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

Contacts

PRINCIPAL_INVESTIGATORSteven Pipe, MD

University of Michigan

Participant flow

Recruitment details

This study was conducted at 33 sites, 17 in the United States, 13 in the European Union, and 3 in the United Kingdom.

Pre-assignment details

A total of 75 participants were screened for the study. Of these, 67 entered the Lead-in Period, while 8 were screening failures.

Participants by arm

Arm	Count
Safety Population 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. After the lead-in phase, subjects received a single-dose of AMT-061.	67
Total	67

Baseline characteristics

Characteristic	Safety Population
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	11 Participants
Age, Categorical Between 18 and 65 years	56 Participants
Age, Continuous	42.8 years STANDARD_DEVIATION 16.2
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	3 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants
Race (NIH/OMB) White	50 Participants
Region of Enrollment Belgium	6 participants
Region of Enrollment Denmark	3 participants
Region of Enrollment Germany	2 participants
Region of Enrollment Ireland	3 participants
Region of Enrollment Italy	5 participants
Region of Enrollment Netherlands	13 participants
Region of Enrollment Sweden	2 participants
Region of Enrollment United Kingdom	7 participants
Region of Enrollment United States	26 participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	67 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 67	0 / 54	2 / 54
other Total, other adverse events	27 / 67	24 / 54	53 / 54
serious Total, serious adverse events	5 / 67	4 / 54	20 / 54

Outcome results

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.

Time frame: Lead-in period and months 7-18 post-treatment of AMT-061

Population: Full Analysis Set (FAS) included all subjects who were enrolled, entered the lead-in phase, were dosed with AMT-061, and provided at least 1 efficacy endpoint assessment for any efficacy endpoint subsequent to AMT-061 dosing. Subjects who were Lead-in Discontinuers were not included in the FAS.

Arm	Measure	Value (MEAN)
FIX (Lead-in)	Annualized Bleeding Rate (ABR) for All Bleeding Episodes	4.19 bleeds/year/subject
AMT-061	Annualized Bleeding Rate (ABR) for All Bleeding Episodes	1.51 bleeds/year/subject

Secondary

ABR for FIX-treated Bleeding Episodes

Time frame: Lead-in and Months 7-18 after AMT-061 dosing

Population: FAS

Arm	Measure	Value (MEAN)
FIX (Lead-in)	ABR for FIX-treated Bleeding Episodes	3.65 bleeds/year/subject
AMT-061	ABR for FIX-treated Bleeding Episodes	0.84 bleeds/year/subject

Secondary

Adjusted Annualized Infusion Rate of FIX Replacement Therapy

Time frame: Lead-in period and months 7-18 after AMT-061 dosing

Population: FAS.

Arm	Measure	Group	Value (MEAN)
FIX (Lead-in)	Adjusted Annualized Infusion Rate of FIX Replacement Therapy	Lead-in	72.49 Infusions/year
AMT-061	Adjusted Annualized Infusion Rate of FIX Replacement Therapy	Months 7-18	2.53 Infusions/year

Secondary

Annualized Exogenous Factor IX Consumption

Time frame: Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing

Population: FAS

Arm	Measure	Group	Value (MEAN)
FIX (Lead-in)	Annualized Exogenous Factor IX Consumption	Lead-in	257,338.8 IU/year
AMT-061	Annualized Exogenous Factor IX Consumption	Months 0-6	12,912.9 IU/year
AMT-061	Annualized Exogenous Factor IX Consumption	Months 7-12	8399.1 IU/year
AMT-061	Annualized Exogenous Factor IX Consumption	Months 13-18	8486.6 IU/year

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.

Time frame: Lead-in period and up to 12 months after AMT-061 dosing

Population: FAS

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
FIX (Lead-in)	EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score	80.9 score on a scale	Standard Error 2.2
AMT-061	EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score	81.0 score on a scale	Standard Error 2.15

Secondary

Factor IX Activity Levels After AMT-061 Dosing

Time frame: Baseline and 6,12, and 18 months after AMT-061 dosing

Population: FAS.

Arm	Measure	Group	Value (MEAN)	Dispersion
AMT-061	Factor IX Activity Levels After AMT-061 Dosing	Baseline	1.19 Factor IX activity (%)	Standard Deviation 0.39
AMT-061	Factor IX Activity Levels After AMT-061 Dosing	6 months	38.95 Factor IX activity (%)	Standard Deviation 18.72
AMT-061	Factor IX Activity Levels After AMT-061 Dosing	12 months	41.48 Factor IX activity (%)	Standard Deviation 21.71
AMT-061	Factor IX Activity Levels After AMT-061 Dosing	18 months	36.90 Factor IX activity (%)	Standard Deviation 21.4

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.

Time frame: Lead-in period and up to 12 months after AT-01 dosing

Population: FAS

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
FIX (Lead-in)	International Physical Activity Questionnaire (iPAQ) Overall Score	4548.1 MET minutes/week	Standard Error 512.38
AMT-061	International Physical Activity Questionnaire (iPAQ) Overall Score	3826.9 MET minutes/week	Standard Error 480.44

Secondary

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

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
AMT-061	Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing	Baseline	1.15 Factor IX activity (%)	Standard Deviation 0.36
AMT-061	Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing	6 months	40.61 Factor IX activity (%)	Standard Deviation 18.64
AMT-061	Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing	12 months	44.82 Factor IX activity (%)	Standard Deviation 23.21
AMT-061	Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing	18 months	39.87 Factor IX activity (%)	Standard Deviation 24.08

Secondary

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

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
AMT-061	Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing	Baseline	1.24 Factor IX activity (%)	Standard Deviation 0.44
AMT-061	Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing	6 months	35.91 Factor IX activity (%)	Standard Deviation 19.02
AMT-061	Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing	12 months	35.54 Factor IX activity (%)	Standard Deviation 17.84
AMT-061	Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing	18 months	31.14 Factor IX activity (%)	Standard Deviation 13.75

Secondary

Number of Adverse Events

Follow up and assess any adverse events reported for safety

Time frame: 5 years

Secondary

Number of Joint Bleeding Episodes

Time frame: Lead-in period and months 7-18 after AMT-061 dosing

Population: FAS

Arm	Measure	Group	Value (NUMBER)
FIX (Lead-in)	Number of Joint Bleeding Episodes	Lead-in	77 Number of bleeds
AMT-061	Number of Joint Bleeding Episodes	Months 7-18	19 Number of bleeds

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.

Time frame: Up to 18 months after AT-061 dosing

Population: FAS

Arm	Measure	Group	Value (NUMBER)
AMT-061	Number of New Target Joints and the Number of New Target Joints Resolved.	New target joints	1 Joints
AMT-061	Number of New Target Joints and the Number of New Target Joints Resolved.	New target joints resolved	0 Joints

Secondary

Number of Spontaneous Bleeding Episodes

Time frame: Lead-in period and months 7-18 after AMT-061 dosing

Population: FAS

Arm	Measure	Group	Value (NUMBER)
FIX (Lead-in)	Number of Spontaneous Bleeding Episodes	Lead-in	50 Number of bleeds
AMT-061	Number of Spontaneous Bleeding Episodes	Months 7-18	14 Number of bleeds

Secondary

Percentage of Subjects With Trough FIX Activity <12% of Normal

Time frame: Lead-in and 3, 12, and 18 months after AMT-061 dosing

Population: FAS

Arm	Measure	Group	Value (NUMBER)
FIX (Lead-in)	Percentage of Subjects With Trough FIX Activity <12% of Normal	Lead-in	79.6 percentage of participants
AMT-061	Percentage of Subjects With Trough FIX Activity <12% of Normal	12 months	8.0 percentage of participants
AMT-061	Percentage of Subjects With Trough FIX Activity <12% of Normal	3 months	7.8 percentage of participants
AMT-061	Percentage of Subjects With Trough FIX Activity <12% of Normal	18 months	6.0 percentage of participants

Secondary

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

Population: FAS

Arm	Measure	Value (NUMBER)
FIX (Lead-in)	Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing	25.9 percentage of participants
AMT-061	Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing	63.0 percentage of participants

Secondary

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

Population: FAS

Arm	Measure	Value (NUMBER)
FIX (Lead-in)	Percent of Subjects Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 Dosing	96.3 percentage of participants

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

Conditions

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Related papers

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Study design

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Eligibility

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Secondary

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Participant flow

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Baseline characteristics

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Outcome results

Annualized Bleeding Rate (ABR) for All Bleeding Episodes

ABR for FIX-treated Bleeding Episodes

Adjusted Annualized Infusion Rate of FIX Replacement Therapy

Annualized Exogenous Factor IX Consumption

EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score

Factor IX Activity Levels After AMT-061 Dosing

International Physical Activity Questionnaire (iPAQ) Overall Score

Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing

Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing

Number of Adverse Events

Number of Joint Bleeding Episodes

Number of New Target Joints and the Number of New Target Joints Resolved.

Number of Spontaneous Bleeding Episodes

Percentage of Subjects With Trough FIX Activity <12% of Normal

Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing

Percent of Subjects Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 Dosing