Hemophilia A
Conditions
Brief summary
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_PRODUCTNXT007
NXT007 will be administered subcutaneously (SC) using an integrated drug-device combination product.
DRUGEmicizumab
Emicizumab will be administered subcutaneously (SC) using vial and syringe.
Sponsors
Hoffmann-La Roche
Chugai Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annualized Bleed Rate (ABR) for Treated Bleeds Over the Main Study Treatment Period | From Month 2 until the clinical cutoff date (at least 7 months of study treatment) |
Secondary
| Measure | Time frame |
|---|---|
| ABR for All Bleeds Over the Main Study Treatment Period | 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 | 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 | 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 | Month 8 |
| ABR for Treated Target Joint Bleeds Over the Main Study Treatment Period | 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 | 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 | 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 | 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 | 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 | Month 8 |
| Change From Baseline in Preoccupation Domain Score of the CATCH Questionnaire (Adult and Adolescent Versions) | 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) | At prespecified timepoints from Baseline until Study Completion (approximately 3.5 years) |
| Change From Baseline in Recreational Activity Impact Domain Score of the CATCH Questionnaire (Adult and Adolescent Versions) | At prespecified timepoints from Baseline until Study Completion (approximately 3.5 years) |
| Physical Impact Domain Score of the Treatment Administration Satisfaction Questionnaire (TASQ) at Specified Timepoints | At prespecified timepoints from Baseline to Month 4 |
| Incidence and Severity of Adverse Events, With Severity Determined According To National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5.0) Grading Scale | From Baseline until Study Completion (approximately 3.5 years) |
| Incidence and Severity of Thromboembolic Events and Thrombotic Microangiopathy | From Baseline until Study Completion (approximately 3.5 years) |
| Incidence and Severity of Injection-Site Reactions | From Baseline until Study Completion (approximately 3.5 years) |
| Incidence of Adverse Events Leading to Discontinuation of Assigned Study Treatment | From Baseline until Study Completion (approximately 3.5 years) |
| Incidence of Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions | From Baseline until Study Completion (approximately 3.5 years) |
| Plasma Concentration of NXT007 | At prespecified timepoints from Baseline to Study Completion (approximately 3.5 years) |
| Percentage of Participants With Anti-Drug Antibodies (ADAs) Against NXT007 at Baseline and During the Study | At prespecified timepoints from Baseline to Study Completion (approximately 3.5 years) |
| Percentage of Participants With Neutralizing ADAs Against NXT007 | At prespecified timepoints from Baseline to Study Completion (approximately 3.5 years) |
Countries
Israel, Japan, Spain, United States
Contacts
CONTACTReference Study ID Number: BO45887 https://forpatients.roche.com/ No attachments to email below.
CONTACTFastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed