Nonsense mutation Mucopolysaccharidosis Type I MedDRA version: 20.1 Level: PT Classification code 10056886 Term: Mucopolysaccharidosis I System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ATALUREN
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Concentration unit: mg mi
Sponsors
PTC Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Evidence of signed and dated informed consent document(s) indicating that the study candidate (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible institutional review board/independent ethics committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the patient should be followed. 2. Age =2 years. 3. Clinical diagnosis of MPS I, confirmed by measurable clinical signs and symptoms of MPS Iand a documented fibroblast or leukocyte a-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory. 4. Documentation of the presence of a nonsense mutation in at least 1 allele of the a L iduronidase (IDUA) gene. 5. Verification that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the IDUA gene. 6. Confirmed screening laboratory values within the central laboratory ranges specified in the protocol Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior BMT/HSCT. 2. Treatment with ERT within 2 months prior to enrollment. 3. Any change (initiation, change in type of drug, dose modifications, schedule modifications, interruption, discontinuation, or re-initiation) in chronic treatment for MPS within 2 months prior to start of Screening. 4. Exposure to another investigational drug within 3 months prior to enrollment. 5. Ongoing participation in any other therapeutic clinical trial. 6. Is pregnant or lactating. Female patients of childbearing potential must have a negative pregnancy test [ß-human chronic gonadotropin (hCG)] at Screening. 7. Ongoing warfarin, phenytoin or tolbutamide therapy. 8. Ongoing IV aminoglycoside use. 9. Ongoing immunosuppressive therapy (other than corticosteroids). 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 patient, makes it unlikely that the course of study drug administration or follow-up would be completed, or could impair the assessment of study results. 12. 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). 13. Surgery within 30 days prior to enrollment, or anticipated surgery during study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether treatment with ataluren can reduce urinary GAG levels in patients with nmMPS I, as assessed by the conventional method for assessing GAG levels in liquid urine;Secondary Objective: • To characterize the safety profile of ataluren in patients with nmMPS I • To evaluate the PK of ataluren in patients with nmMPS I ;Primary end point(s): Change in urinary GAG levels (total and subtypes, eg, DS and HS) in each dose cycle, as assessed by the conventional method for assessing GAG levels in liquid urine.;Timepoint(s) of evaluation of this end point: Days 42, 112 and 182 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall safety profile of ataluren characterized by type, frequency, severity, timing, and relationship to study drug of any adverse events; new physical examination, laboratory test, or electrocardiogram (ECG) abnormalities; drug discontinuations due to adverse events; and serious adverse events (SAEs) • Ataluren plasma concentrations before and 2 hours after morning drug administration at the beginning of each cycle and before and 2, 4, and 6 hours after morning drug administration at the end of each cycle, as assessed by a validated bioanalytical method. ;Timepoint(s) of evaluation of this end point: Safety: Every visit PK: day 1, 42, 70, 112, 140 and 182 | — |
Countries
Germany, United Kingdom
Contacts
Public ContactMedpace Regulatory Submissions
Medpace Germany GmbH
Outcome results
None listed