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

NCT03569891 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: CSL222_3001 (CT-AMT-061-02)CT-AMT-061-022017-004305-402024-510738-42-00
• Study Type: interventional
• Target: 67
• Locations: 8 countries
• Sites: 33

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

• Factor IX Activity Levels After AMT-061 (CSL222) Dosing

  At Baseline, 6, 12, and 18 months after AMT-061 (CSL222) dosing

• Annualized Exogenous FIX Consumption

  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

Study Arms (2)

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.

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.

Biological: Factor IX (FIX)

Interventions

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.

FIX replacement (Lead-in Period)

AAV5-hFIXco-Padua GENETIC

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

Also known as: AMT-061, etranacogene dezaparvovec

AMT-061

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (33)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Los Angeles Orthopedic Hospital

Los Angeles, California, 90007, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of California, San Diego

San Diego, California, 92161, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center Hematology and Oncology

Washington D.C., District of Columbia, 20010, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Hemophilia Center of Western New York

Buffalo, New York, 14209, United States

Location

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Health Science Center & Medical School

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Washington Institute for Coagulation

Seattle, Washington, 98101, United States

Location

Bloodworks Northwest

Seattle, Washington, 98104, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

University Hospital Leuven

Leuven, 3000, Belgium

Location

Righospitalet

Copenhagen, 2100, Denmark

Location

Vivantes Klinikum im Friedrichshain

Berlin, 10249, Germany

Location

Klinikum der Johann Wolfgang Goethe Universitat

Frankfurt am Main, 60590, Germany

Location

National Coagulation Centre, St James's Hospital

Dublin, D08 A978, Ireland

Location

Amsterdam UMC - Locatie AMC

Amsterdam, 1105 AZ, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Erasmus MC

Rotterdam, 3015 CE, Netherlands

Location

UMC Utrecht, Van Creveldkliniek

Utrecht, 3508 GA, Netherlands

Location

Center for Thrombosis and Hemostasis Skåne University Hospital Malmö

Malmo, SE-205 02, Sweden

Location

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

Cambridge, CB2 0QQ, United Kingdom

Location

The Royal London Hospital (Barts Health NHS Trust)

London, E1 2ES, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 41358585 DERIVED

• 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.

  PMID: 39341368 DERIVED

• 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.

  PMID: 38437857 DERIVED

• 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.

  PMID: 36812434 DERIVED

MeSH Terms

Conditions

Hemophilia B; Hemorrhage; Hemophilia A

Interventions

Factor IX

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Clinical Study Disclosure Manager
• Organization: CSL Behring

clinicaltrials@cslbehring.com

1-610-878-4697

Study Officials

• Steven Pipe, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The reference therapy is prophylactic factor IX replacement therapy used during the lead-in phase prior to treatment with AAV5-hFIXco-Padua (AMT-061).

Study Record Dates

• First Submitted: June 14, 2018
• First Posted: June 26, 2018
• Study Start: June 27, 2018
• Primary Completion: September 22, 2021
• Study Completion: March 19, 2025
• Last Updated: March 27, 2026
• Results First Posted: October 10, 2022

Record last verified: 2026-02

Locations

DK (1); NL (4); DE (2); SE (1); US (19); BE (2); GB (3); IE (1)