E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Disease in which clotting factor VIII (FVIII) is deficient or inactive, leading to increased tendency to bleed |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060612 |
E.1.2 | Term | Hemophilia A |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate factor VIII (FVIII) inhibitor development, defined as an inhibitor titer of greater than or equal to (>=)0.6 Bethesda units (BU) using the Nijmegen modification of the Bethesda assay and confirmed by the central laboratory, in subjects treated with Xyntha in usual use. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the overall safety of Xyntha in this subject population. Product safety will be assessed through the collection of nonserious adverse events (AEs) and serious adverse events (SAEs) as well as the incidence of less-than-expected therapeutic effect (LETE). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male subjects >=12 years of age with hemophilia A.
2. Subjects transitioned to Xyntha from ReFacto or other recombinant or plasma-derived FVIII replacement products.
3. Treatment history of greater than (>) 150 exposure days (EDs) to any recombinant or plasma-derived FVIII replacement products prior to the Enrollment Visit.
4. Negative inhibitor at screening or documentation of a negative inhibitor titer (less than (<) 0.6 BU) using the Nijmegen modification of the Bethesda assay (or alternative assay for FVIII inhibitor) obtained within 6 weeks or less prior to the signing of the informed consent/assent form except for subjects entering the study on immune tolerance induction therapy. If the Nijmegen modification of the Bethesda assay is not available to the investigative site, the site must indicate which assay method is being used in the study source documents.
5. Documented Human immunodeficiency virus (HIV)-positive subjects must have Cluster of Differentiation 4 (CD4) count >200 per microliter (>200/μL) confirmed within 6 months prior to the Enrollment Visit. |
|
E.4 | Principal exclusion criteria |
1. Presence of any bleeding disorder in addition to hemophilia A.
2. Inhibitor titer of >=0.6 BU (preferably using the Nijmegen modification of the Bethesda assay) during the screening period except for subjects on immune tolerance induction therapy.
3. Treatment with immunomodulatory therapy (e.g. intravenous immunoglobulin [IVIG], routine systemic corticosteroids, cyclosporins, anti-TNF agents) during the screening period.
4. Treatment with any investigational agent or device within 30 days of the Enrollment Visit.
5. Known hypersensitivity to hamster protein.
6. Any condition(s) that compromises the subject’s ability to comply with and/or perform study-related activities or that poses a clinical contraindication to study participation (these conditions include, but are not limited to inadequate medical history to assure study eligibility; inability to properly store study drug; and expectation of poor compliance with study-related procedure).
7. Unwilling or unable to follow the terms of the protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Subjects With Factor VIII (FVIII) Inhibitor Development |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Month 24 or early withdrawal |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
New Zealand |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 11 |