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

NCT ID: NCT03569891

Last Updated: 2025-05-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

67 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-27

Study Completion Date

2025-03-19

Brief Summary

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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.

Detailed Description

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Conditions

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Hemophilia B

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

AAV5-hFIXco-Padua

Intervention Type GENETIC

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

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.

Group Type ACTIVE_COMPARATOR

Factor IX (FIX)

Intervention Type 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.

Interventions

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AAV5-hFIXco-Padua

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

Intervention Type GENETIC

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.

Intervention Type BIOLOGICAL

Other Intervention Names

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AMT-061 etranacogene dezaparvovec

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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CSL Behring

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Steven Pipe, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Los Angeles Orthopedic Hospital

Los Angeles, California, United States

Site Status

Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status

University of California, Davis

Sacramento, California, United States

Site Status

University of California, San Diego

San Diego, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Children's National Medical Center Hematology and Oncology

Washington D.C., District of Columbia, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Hemophilia Center of Western New York

Buffalo, New York, United States

Site Status

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Tennessee Health Science Center

Memphis, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas Health Science Center & Medical School

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Washington Institute for Coagulation

Seattle, Washington, United States

Site Status

Bloodworks Northwest

Seattle, Washington, United States

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

University Hospital Leuven

Leuven, , Belgium

Site Status

Righospitalet

Copenhagen, , Denmark

Site Status

Vivantes Klinikum im Friedrichshain

Berlin, , Germany

Site Status

Klinikum der Johann Wolfgang Goethe Universitat

Frankfurt am Main, , Germany

Site Status

National Coagulation Centre, St James's Hospital

Dublin, , Ireland

Site Status

Amsterdam UMC - Locatie AMC

Amsterdam, , Netherlands

Site Status

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

UMC Utrecht, Van Creveldkliniek

Utrecht, , Netherlands

Site Status

Center for Thrombosis and Hemostasis Skåne University Hospital Malmö

Malmo, , Sweden

Site Status

The Cambridge Haemophilia and Thrombophilia Centre Camridge University Hospitals NHS Foundation Trust - Box 217 Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

The Royal London Hospital (Barts Health NHS Trust)

London, , United Kingdom

Site Status

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status

Countries

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United States Belgium Denmark Germany Ireland Netherlands Sweden United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39341368 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38437857 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36812434 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CSL222_3001 (CT-AMT-061-02)

Identifier Type: -

Identifier Source: org_study_id

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