Mucopolysaccharidosis Type I (MPS I)

Full Study Name

CNS Unmet Medical Need in Mucopolysaccharidosis: A Phase 2Safety and Pharmacokinetics Study of Ataluren

Study ID



PTC Therapuetics Inc.

Local Principal Investigator

Simon Jones

Study Status


Main Aims

The primary objectives of this study are to:

  • Characterize the safety profile of ataluren in patients with nonsense mutation MPS I (nmMPSI)
  • Evaluate the CSF and plasma PK of ataluren in patients with nonsense mutation MPS I (nmMPSI)
Inclusion Criteria
  • Age ≥2 years.
  • Clinical diagnosis of MPS I, confirmed by measurable clinical signs and symptoms of MPS I and a fibroblast or leukocyte α-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.
  • Documentation of the presence of a nonsense mutation in at least 1 allele of the α-L-iduronidase (IDUA) gene.
  • Verification that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the IDUA gene.
  • Confirmed screening laboratory values within the central laboratory ranges specified
  • 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
Exclusion Criteria
  • 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.
  • Exposure to another investigational drug or (intrathecal/spinal) device within 3 months prior to enrollment.
  • Ongoing participation in any other therapeutic clinical trial.
  • 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.
  • The patient is unable to provide a CSF sample due to an opening CSF pressure that exceeds 30.0 cm H2O.
  • 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.
  • Is pregnant or lactating. Female patients of childbearing potential must have a negative pregnancy test [β-human chronic gonadotropin (hCG)] at screening.
  • 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.
  • 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).
  • Surgery within 30 days prior to enrollment, or anticipated surgery during study participation.
  • 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)
    • Ongoing IV aminoglycoside use.