E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonsense-Mutation-Mediated Hemophilia A and B |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060613 |
E.1.2 | Term | Hemophilia A (Factor VIII) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060614 |
E.1.2 | Term | Hemophilia B (Factor IX) |
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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 |
To determine whether ataluren provides pharmacological effect in nonsense-mutation-mediated HA/HB as measured by plasma FVIII/FIX activity. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of ataluren on additional markers of disease activity. • To characterize the safety profile of ataluren in subjects with nonsense-mutation-mediated HA/HB (including the occurrence of any inhibitory anti-FVIII/FIX antibodies in serum). • To determine compliance with ataluren administration. • To assess ataluren plasma exposure in subjects with nonsense-mutation-mediated HA/HB. • To document the occurrence of bleeding episodes. • To document the use of exogenous FVIII/FIX concentrate. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of signed and dated informed consent document(s) indicating that the subject has been informed of all pertinent aspects of the study. 2. Age ≥18 years. 3. Male sex. 4. Presence of a nonsense mutation as the sole disease-causing mutation in the f8 or f9 gene 5. Verification that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the f8/f9 gene. Note: A subject who has written documentation of a nonsense mutation as the cause for hemophilia need not wait for confirmatory results to start ataluren as long as the confirmatory genotyping blood sample has been drawn. 6. At least 20 exposure-days of treatment with FVIII/FIX concentrate. 7. Confirmed screening laboratory values within the ranges specified in Table 1 of page 34 in the protocol. Note: Confirmation should be performed for out-of-range values to determine if the abnormality is real or artifactual. Values used to establish eligibility should be obtained within the screening period, and should generally be the most recent measurement obtained. 8. Willingness, if not surgically sterile, to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and follow-up periods. 9. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered. |
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity to any of the ingredients or excipients of the study drug (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate). 2. Unable or unwilling to forego prophylactic FVIII/FIX concentrate use during the screening and on-study periods. Note: Subjects are allowed use of FVIII/FIX for treatment of bleeding episodes while on study. 3. Any history of prior anti-FVIII/FIX inhibitors as determined by Bethesda assay. 4. Exposure to another investigational drug within 30 days prior to start of ataluren administration. 5. Ongoing coumarin anti-coagulants, phenytoin, or tolbutamide therapy. 6. History of anti-hepatitis C therapy within 14 days prior to start of ataluren administration. 7. History of major surgical procedure within 30 days prior to start of ataluren administration. 8. Receiving study drug in any other therapeutic clinical trial. 9. History of coagulation abnormalities other than HA/HB. 10. Known portal hypertension. 11. Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject, makes it unlikely that the course of study drug administration or follow-up would be completed, or could impair the assessment of study results. Note: Patients with human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C may be enrolled as long as they meet all entry criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects with a plasma FVIII/FIX activity response; a plasma FVIII/FIX activity response is defined as an end-of-treatment activity of ≥1% as determined by functional assay. |
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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 | No |
E.6.3 | Therapy | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | Information not present in EudraCT |
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 |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 15 |