Nonsense mutation Mucopolysaccharidosis Type I MedDRA version: 18.1 Level: PT Classification code 10056886 Term: Mucopolysaccharidosis I System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
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 I and a 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, with clinically stable disease. 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 7. In patients who are sexually active, willingness, if not surgically sterile, to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and for 60 days after the last ataluren administration. 8. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures (including lumbar punctures), and study restrictions. Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any change (initiation, change in type of drug, dose modification [not weight based], schedule modification, interruption, discontinuation, or re-initiation) in ERT within 6 months prior to start of screening. 2. Exposure to another investigational drug or (intrathecal/spinal) device within 3 months prior to enrollment. 3. Ongoing participation in any other therapeutic clinical trial. 4.The patient is unable to have a lumbar puncture performed due to severe musculoskeletal/spinal abnormalities, risk of abnormal bleeding, or the presence of a ventriculoperitoneal shunt. 5. The patient is unable to provide a CSF sample due to an opening CSF pressure that exceeds 30.0 cm H2O. 6. The patient has any known or suspected hypersensitivity to anesthesia that is thought to be by a physician or anesthesiologist as an unacceptably high risk for anesthesia due to compromised airways or other conditions. 7. Is pregnant or lactating. Female patients of childbearing potential must have a negative pregnancy test [ß-human chronic gonadotropin (hCG)] at screening. 8. Ongoing use of the following drugs: Drugs metabolized by CYP2C8 (eg, paclitaxel) or CYP2C9 (eg, coumarin anticoagulants [warfarin], phenytoin or tolbutamide) Drugs that are inhibitors of breast cancer resistant protein (BCRP) (eg, cyclosporine, eltrombopag, geftinib). Note: Topical cyclosporine therapy is permitted. Drugs that are substrates of UGT1A9 (eg, propofol, mycophenolate mofetil), OAT1, OAT3, or OATP1B3 (eg, oseltamivir, acyclovir, captopril, furosemide, bumetanide, valsartan, pravastatin, rosuvastatin, atorvastatin, pitavastatin) Drugs that are general inhibitors of UGT (eg, probenecid, valproic acid) 9. Ongoing IV aminoglycoside use. 10. 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. 11. 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). 12. Surgery within 30 days prior to enrollment, or anticipated surgery during study participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Characterize the safety profile of ataluren in patients with nmMPS I - Evaluate the CSF and plasma PK of ataluren in patients with nmMPS I ; Secondary Objective: • Evaluate CSF GAG levels in patients with nmMPS I following ataluren treatment • Evaluate urinary GAG levels in patients with nmMPS I, following ataluren treatment • Evaluate plasma GAG levels in patients with nmMPS I following ataluren treatment ; Primary 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 CSF concentrations as assessed by a validated bioanalytical method • Ataluren plasma concentrations before and 2, 4, and 6 hours after morning drug administration at Day 1 and every 6 weeks during treatment, as assessed by a validated bioanalytical method. ; Timepoint(s) of evaluation of this end point: Safety: Every visit CSF PK: Day 1, 85 Plasma PK: Day 1, 43, 85, and 113 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in CSF GAG levels from pretreatment to end of treatment - Change in urinary GAG levels from pretreatment to end of treatment ; Timepoint(s) of evaluation of this end point: Urinary GAG Levels: Every visit Plasma GAG Levels: Screening, and Days 1, 43, 85, 113, and End of Treatment F/U | — |
Countries
United Kingdom
Contacts
Public ContactMedpace Regulatory Submissions
Medpace Germany GmbH
Outcome results
None listed