A Clinical Study to Evaluate the Effects of NXT007 Compared to Emicizumab Prophylaxis in People With Hemophilia A

Official title

A Multicenter, Randomized, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of NXT007 Prophylaxis Versus Emicizumab Prophylaxis in People With Hemophilia A

Overview

The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of NXT007 prophylaxis compared with emicizumab prophylaxis in people age 12 years and older with severe or moderate congenital hemophilia A without factor VIII (FVIII) inhibitors or with hemophilia A of any severity (severe, moderate, and mild) with FVIII inhibitors.

Interventions

• Combination product NXT007
  NXT007 will be administered subcutaneously (SC) using an integrated drug-device combination product.
• Drug Emicizumab
  Emicizumab will be administered subcutaneously (SC) using vial and syringe.

Primary outcome measures

• Annualized Bleed Rate (ABR) for Treated Bleeds Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]

Secondary outcome measures (12)

• ABR for All Bleeds Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]
• ABR for Treated Spontaneous Bleeds Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]
• ABR for Treated Joint Bleeds Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]
• Adjusted Mean Treatment Burden Domain Score in Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) Questionnaire - Adult Version at Month 8 [Time frame: Month 8]
• ABR for Treated Target Joint Bleeds Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]
• Percentage of Participants with Zero Treated Bleeds Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]
• Number of Injections and Dose per Bleed of Coagulation Factors or Bypassing Agent Administered to Treat a Bleed Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]
• Annualized Injection Rate of FVIII or Bypassing Agent Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]
• Annualized Consumption Rate of FVIII or Bypassing Agent Over the Main Study Treatment Period [Time frame: From Month 2 until the clinical cutoff date (at least 7 months of study treatment)]
• Mean Treatment Burden Domain Score in CATCH Questionnaire - Adolescent Version at Month 8 [Time frame: Month 8]
• Change From Baseline in Preoccupation Domain Score of the CATCH Questionnaire (Adult and Adolescent Versions) [Time frame: At prespecified timepoints from Baseline until Study Completion (approximately 3.5 years)]
• Change From Baseline in Social Activity Impact Domain Score of the CATCH Questionnaire (Adult and Adolescent Versions) [Time frame: At prespecified timepoints from Baseline until Study Completion (approximately 3.5 years)]

Eligibility criteria

Inclusion criteria

• Diagnosis of severe (FVIII:C <1 International Unit per decilitre \[IU/dL\]) or moderate (FVIII:C between ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A with or without inhibitors against FVIII
• Diagnosis of mild (FVIII:C between >5 IU/dL and <40 IU/dL) congenital hemophilia A with chronic FVIII inhibitors, defined as documented FVIII inhibitor ( ≥0.6 BU/mL or ≥1.0 BU/mL only for laboratories with a historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) and chronic reduction of endogenous baseline FVIII:C to <5 IU/dL for ≥12 months
• Documented historical FVIII inhibitor assay results within the 12 months prior to enrollment
• Documentation of the details of prophylactic and episodic FVIII treatment, bypassing agent (BPA) treatment, emicizumab prophylaxis treatment, and the number and type of bleeding episodes for at least the last 6 months prior to screening
• For potential participants taking on-demand treatments prior to study entry: agreement to move to a prophylaxis treatment with either emicizumab or NXT007, according to assigned randomization

Exclusion criteria

• Sensitivity to any of the study investigations, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study
• Use of systemic immunomodulators (e.g., interferon or rituximab) at the time of enrollment or planned use during the study, except for antiretroviral therapy to treat HIV
• Refusal to accept plasma-derived and/or blood product transfusion support in an emergency scenario
• Planned surgery (excluding minor procedures, such as non-molar tooth extraction or incision and drainage) during the study
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing)
• History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third-degree atrioventricular heart block) or evidence or clinical history of prior myocardial infarction

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Center for Inherited Blood Disorders — Orange
• University of Colorado Hemophilia and Thrombosis Center — Aurora
• St Joseph's Children's Hospital of Tampa — Tampa
• Innovative Hematology, Inc. — Indianapolis
• University Of Iowa Hospitals And Clinics — Iowa City
• Washington Center for Bleeding Disorders — Seattle

Spain · 6 centers

• Hospital Universitario Vall d'Hebron - PPDS — Barcelona
• Hospital de la Santa Creu i Sant Pau — Barcelona
• Hospital Universitario La Paz - PPDS — Madrid
• Hospital Regional Universitario de Malaga ? Hospital General — Málaga
• Hospital Universitario Virgen del Rocio - PPDS — Seville
• Hospital Universitari i Politecnic La Fe de Valencia — Valencia

Japan · 4 centers

• Nagoya University Hospital — Nagoya
• Gunma University Hospital — Maebashi
• Nara Medical University Hospital — Kashihara-shi
• Ogikubo Hospital — Suginami-Ku

Italy · 3 centers

• Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico — Milan
• IRCCS Istituto Clinico Humanitas — Rozzano
• Azienda Ospedaliera Universitaria Careggi — Florence

Belgium · 1 center

• UZ Leuven — Leuven

China · 1 center

• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin

France · 1 center

• Hospices Civils de Lyon — Bron

Germany · 1 center

• Universitätsklinikum Bonn — Bonn

Hungary · 1 center

• Debreceni Egyetem Klinikai Kozpont Nagyerdei Campus — Debrecen

Israel · 1 center

• The Chaim Sheba Medical Center - PPDS — Ramat Gan

Netherlands · 1 center

• Universitair Medisch Centrum Utrecht Cancer Center - PPDS — Utrecht

New Zealand · 1 center

• Auckland City Hospital — Auckland

South Korea · 1 center

• Kyungpook National University Hospital — Daegu

Taiwan · 1 center

• National Taiwan University Hospital — Taipei

United Kingdom · 1 center

• University Hospital of Wales — Cardiff

Identifiers

NCT: NCT07416604 · BO45887 · 2025-522435-33-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗