Treatment for Nonsense Mutation Mucopolysaccharidosis Type I

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2014-002596-28-GB
• Date of registration: 12/06/2015
• Prospective Registration: No
• Primary sponsor: PTC Therapeutics Inc.
• Public title: Treatment for Nonsense Mutation Mucopolysaccharidosis Type I
• Scientific title: A Phase 2 Study of Ataluren (PTC124) as Treatment for Nonsense Mutation Mucopolysaccharidosis Type I
• Date of first enrolment: 28/01/2015
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002596-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, United Kingdom

Contacts

• Name: Medpace Regulatory Submissions
• Affiliation: Medpace Germany GmbH

• Name: Medpace Regulatory Submissions
• Affiliation: Medpace Germany GmbH

Key inclusion & exclusion 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:
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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

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

Intervention(s)

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 milligram(s)
Concentration type: equal
Concentration number: 125, 250 or 1000-

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 milligram(s)
Concentration type: equal
Concentration number: 125, 250 or 1000-

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 milligram(s)
Concentration type: equal
Concentration number: 125, 250 or 1000-

Primary Outcome(s)

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

Timepoint(s) of evaluation of this end point: Days 42, 112 and 182

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.

Secondary Outcome(s)

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

Secondary ID(s)

2014-002596-28-DE

PTC124-GD-024-MPS

Source(s) of Monetary Support

PTC Therapeutics Inc.

Ethics review

Status: Approved
Approval date: 28/01/2015
Contact:

Results

• Results available: Yes
• Date Posted: 31/03/2018
• Date Completed: 20/07/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002596-28/results