Hemophilia A
Conditions
Keywords
Factor VIII, Inhibitors, Bypassing agents
Brief summary
The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of NXT007 prophylaxis in pediatric patients aged 0 to 11 years with severe or moderate congenital hemophilia A without factor VIII inhibitors or congenital hemophilia A of any severity (severe, moderate, and mild) with inhibitors (emicizumab-naïve and treated). Patients with hemophilia A aged ≥12 to \<18 years old with a body weight of \<40 kilograms (kg) are also able to participate.
Interventions
DRUGNXT007
NXT007 will be administered subcutaneously (SC) according to the schedule in the protocol.
Sponsors
Hoffmann-La Roche
Chugai Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Age \<12 years at the time of signing Informed Consent Form; or age ≥12 and \<18 years with body weight \<40 kg * Diagnosis of severe (Factor VIII coagulation protein activity \[FVIII:C\] \<1 International Unit per decilitre \[IU/dL\]) or moderate (FVIII:C between ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A (HA) with or without inhibitors against factor VIII (FVIII) * For potential participants with moderate HA without inhibitors, fulfillment of at least one of the following criteria: Current prophylaxis with long-term prophylaxis intention due to a severe bleed phenotype; For those not treated with prophylaxis: at least one traumatic joint or critical muscle bleed in the last 6 months or ≥2 spontaneous bleeds/year or 5 bleeds/year, including traumatic bleeds; Signs of joint degeneration compatible with hemophilic arthropathy (e.g., subchondral bone changes or the presence of synovitis) as assessed by any imaging assessment (e.g., ultrasound, MRI, radiograph); Bleeding at a critical site (e.g., intracranial). * 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 * 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 if appropriate * For potential participants taking on-demand treatments prior to study entry: agreement to move to a prophylaxis treatment with NXT007 * Adequate renal, hepatic, and hematologic function, as defined in the protocol
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 * History or conditions, other than HA, which may indicate hypo- or hypercoagulopathy risk * 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) * Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
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) |
| 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 Factor VIII 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) |
| Change from Baseline in the Treatment Burden Domain Score on the Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) 2.0 Caregiver Questionnaire at Month 8 | Baseline and Month 8 |
| Change from Baseline in the Preoccupation Domain Score on the CATCH 2.0 Caregiver Questionnaire at Month 8 | Baseline and Month 8 |
| Incidence and Severity of Adverse Events, With Severity Determined According To National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 Grading Scale | From Baseline until Study Completion (approximately 4 years) |
| Incidence and Severity of Thromboembolic Events and Thrombotic Microangiopathy | From Baseline until Study Completion (approximately 4 years) |
| Incidence and Severity of Injection-Site Reactions | From Baseline until Study Completion (approximately 4 years) |
| Incidence of Adverse Events Leading to Study Drug Discontinuation | From Baseline until Study Completion (approximately 4 years) |
| Incidence of Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions | From Baseline until Study Completion (approximately 4 years) |
| Plasma Concentrations of NXT007 | At prespecified timepoints from Baseline until Study Completion (approximately 4 years) |
| Percentage of Participants With Anti-Drug Antibodies (ADAs) Against NXT007 at Baseline and During the Study | At prespecified timepoints from Baseline until Study Completion (approximately 4 years) |
| Percentage of Participants With Neutralizing ADAs Against NXT007 | At prespecified timepoints from Baseline until Study Completion (approximately 4 years) |
Contacts
CONTACTReference Study ID Number: BO45888 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