Nonsense-Mutation-Mediated Hemophilia A and B MedDRA version: 12.1 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) MedDRA version: 12.1 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX)
Conditions
Interventions
291844
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Prop
291844
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Prop
Sponsors
PTC Therapeutics, Inc
Eligibility
Sex/Gender
Male
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether ataluren provides pharmacological effect in nonsense-mutation-mediated HA/HB as measured by plasma FVIII/FIX activity.;Secondary Objective: • 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.;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. | — |
Countries
France
Outcome results
None listed