Phase 3
Completed N=67
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients
Source: ClinicalTrials.gov NCT03569891 ↗Enrolled (actual)
67
Serious AEs
16.6%
Results posted
Oct 2022
Primary outcomePrimary: Annualized Bleeding Rate (ABR) for All Bleeding Episodes — 4.19; 1.51 bleeds/year/participants
◆ Published Evidence
Highly cited
363citations · ~121 / year
Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B.
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.
Linked Publications (4)
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Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B.
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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.
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Final Analysis of a Study of Etranacogene Dezaparvovec for Hemophilia B.
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Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Bleeding Rate (ABR) for All Bleeding Episodes |
4.19; 1.51 | — |
| SECONDARY Factor IX Activity Levels After AMT-061 (CSL222) Dosing |
1.19; 38.95; 41.48; 36.90 | — |
| SECONDARY Annualized Exogenous FIX Consumption |
257,338.8; 12,912.9; 8399.1; 8486.6 | — |
| SECONDARY Adjusted Annualized Infusion Rate of FIX Replacement Therapy |
72.49; 2.53 | — |
| SECONDARY Percent of Participants Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 (CSL222) Dosing |
96.3 | — |
| SECONDARY Percentage of Participants With Trough FIX Activity <12% of Normal |
79.6; 7.8; 8.0; 6.0 | — |
| SECONDARY ABR for FIX-treated Bleeding Episodes |
3.65; 0.84 | — |
| SECONDARY Annualized Rate of Spontaneous Bleeding Episodes |
1.52; 0.44 | — |
| SECONDARY Annualized Rate of Joint Bleeding Episodes |
2.35; 0.51 | — |
| SECONDARY Mean FIX Activity (%) in Participants With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 (CSL222) Dosing |
1.24; 35.91; 35.54; 31.14 | — |
| SECONDARY Mean FIX Activity (%) in Participants Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 (CSL222) Dosing |
1.15; 40.61; 44.82; 39.87 | — |
| SECONDARY Number of New Target Joints and the Number of New Target Joints Resolved |
1; 0 | — |
| SECONDARY Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 (CSL222) Dosing |
25.9; 63.0 | — |
| SECONDARY International Physical Activity Questionnaire (iPAQ) Overall Score |
4548.1; 3826.9 | — |
| SECONDARY EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score |
80.9; 81.0 | — |
| SECONDARY Number of Participants With Adverse Events |
54 | — |
| SECONDARY Number of Participants With Change (Shift) in Abdominal Ultrasound Results From Normal, Abnormal and Missing to Abnormal Post Treatment |
21; 22; 1 | — |
| SECONDARY Number of Participants With Anti-AAV5 Antibodies |
49; 8; 50 | — |
| SECONDARY Number of Participants With AAV5 Capsid-specific T Cells |
5 | — |
| SECONDARY Number of Participants With Anti-FIX Antibodies |
48; 1 | — |
| SECONDARY Number of Participants With FIX Inhibitors and Recovery |
— | — |
| SECONDARY Number of Participants With Increased Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) Levels And Who Used Any Corticosteroids For Treatments |
13; 10; 9 | — |
| SECONDARY Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Laboratory Values |
1; 1; 11; 19; 2 | — |
| SECONDARY Number of Participants With Vector DNA Shedding |
45; 49 | — |
| SECONDARY Number of Participants With Inflammatory Markers |
45; 1; 0; 17; 53 | — |
| SECONDARY Number of Participants With Alpha-fetoprotein (AFP) Levels Above LLOQ at Month 60 |
43 | — |
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
- 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
Data sourced from ClinicalTrials.gov (NCT03569891) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.