E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053753 |
E.1.2 | Term | Hemophilia A without inhibitors |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060612 |
E.1.2 | Term | Hemophilia A |
E.1.2 | System Organ Class | 100000004850 |
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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 |
The primary objective of the study is to evaluate safety of rFVIIIFc in previously treated pediatric subjects with hemophilia A. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study in this study population are as follows:
To evaluate the efficacy of rFVIIIFc for prevention and treatment of bleeding episodes.
To evaluate and assess the PK of rFVIIIFc.
To evaluate rFVIIIFc consumption for prevention and treatment of bleeding episodes.
To evaluate the effect of rFVIIIFc based on patient-reported outcomes and health outcomes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Parent or legal guardian to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information. Subjects may provide assent if appropriate.
2. Male, <12 years of age, and weight ≥13 kg.
3. Severe hemophilia A defined as <1 IU/dL (<1%) endogenous FVIII in local laboratory demonstrating <1% Factor IX coagulant activity (FVIII:C) or a documented genotype known to produce severe hemophilia A.
4. Previously treated subject, defined as having at least 50 EDs to any recombinant or plasma-derived FVIII product including cryoprecipitate (blood products including fresh frozen plasma treatment must not be considered in the count of the documented EDs).
5. In case of known to be HIV positivity:
a. platelet count ≥100,000 plts/μL
b. CD4 count ≥200 cells/μL
c. viral load of <400 copies/mL
6. No history of, or currently detectable, inhibitor.
7. No measurable inhibitor activity using the Nijmegen-modified Bethesda assay (≥0.6 BU/mL is considered positive) at Screening.
8. Willingness and ability of the subject‟s parent or legal guardian to complete training and use EPD throughout the study. |
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E.4 | Principal exclusion criteria |
1. Other coagulation disorder(s) in addition to hemophilia A.
2. History of anaphylaxis associated with any FVIII or IV immunoglobulin administration.
3. Active renal disease (per the discretion of the Investigator and medical records).
4. Active hepatic disease (per the discretion of the Investigator and medical records).
5. Any concurrent clinically significant major disease that, in the opinion of the Investigator, would make the subject unsuitable for enrollment.
6. Current systemic treatment with chemotherapy and/or other immunosuppressant drugs, with the following exceptions: use of steroids for treatment of asthma or management of acute allergic episodes, and routine immunizations.
7. Participation within the past 30 days in any other clinical study involving investigational drugs.
8. Surgery within 30 days prior to the Screening Visit (visit can be re-scheduled and subject screened). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The occurrence of inhibitor development. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
On every scheduled clinic visit by Nijmegen-modified Bethesda Assay. |
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E.5.2 | Secondary end point(s) |
Efficacy and safety endpoints:
- The number of annualized bleeding episodes (spontaneous and traumatic) per subject
- The number of annualized spontaneous joint bleeding episodes per subject
- Assessments of response to treatment with rFVIIIFc for bleeding episodes, using the 4-point bleeding response scale
- Total annualized rFVIIIFc consumption per subject for prevention and treatment of bleeding episodes
- Time from last injection of rFVIIIFc to the bleeding episode
- Number of injections and dose per injection of rFVIIIFc required to resolve a bleeding episode (joint, soft tissue, and muscle)
Pharmakokinetic endpoints:
- Primary PK endpoints: Cmax, half-life, CL, Vd, AUC, MRT and incremental recovery
Patient Reported and Health Outcome Endpoints Related to Hemophilia:
- Canadian Hemophilia Outcomes-Kid's Life Assessment Tool:
Children, Proxi for parents
- Hemo-Sat Patient Satisfaction Scale for parents
- EQ-5D Youth for children
- number of hospitalisation visits
- number of Emergency Room visits
- number of non-study related physician visits
- number of days off school
- number of days off work for parent |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy and safety endpoints will be measured throughout the study. Pharmacokinetic endpoints will be evaluated in a subgroup of at least 24 patients on the baseline and Day 1 dosing visits. Patient Reported and Health Outcome Endpoints Related to Hemophilia will be evaluated throughout the study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Hong Kong |
Ireland |
Netherlands |
Poland |
South Africa |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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The end of study
• At least 24 subjects (12 subjects <6 years and 12 subjects 6 to <12 years) have adequate PK data
• At least 50 subjects (25 subjects <6 years and 25 subjects 6 to <12 years) have inhibitor results from the central laboratory from testing at 50 EDs or greater
Once the criteria have been met, any additional study subjects will be required to come for the Week 26 assessments at the time of their next scheduled dose and will be eligible to transfer to Study 8HA01EXT.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |