Safety and Efficacy of Ataluren (PTC124) for Cystic Fibrosis

NCT00237380 | Completed Phase 2

• 2 other identifiers: PTC124-GD-005-CF20050188
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

In some participants with cystic fibrosis (CF), the disease is caused by a nonsense mutation (premature stop codon) in the gene that makes the cystic fibrosis transmembrane regulator (CFTR) protein. Ataluren has been shown to partially restore CFTR production in animals with CF due to a nonsense mutation. The main purpose of this study is to understand whether ataluren can safely increase functional CFTR protein in the cells of participants with CF due to a nonsense mutation.

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis; Nonsense mutation; Premature stop codon

Outcome Measures

Primary Outcomes (3)

• Change From Baseline to End of Treatment in Total Chloride Transport

  Baseline of Cycle 1 and Cycle 2, Day 14 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)

• Number of Participants With a Chloride Transport Response

  Baseline of Cycle 1 and Cycle 2 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)

• Number of Participants With a Chloride Transport Normalization Between Baseline and End of Treatment

  Baseline of Cycle 1 and Cycle 2 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)

Secondary Outcomes (12)

• Change From Baseline in Nasal Chloride Secretion as Assessed by Transepithelial Potential Difference (TEPD)

  Baseline of Cycle 1 and Cycle 2, Day 14 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)

• Change From Baseline in Sweat Chloride Concentration as Determined by Pilocarpine Iontophoresis

  Baseline, Day 41

• Change From Baseline in CFTR Protein in Nasal Mucosa as Determined by Immunofluorescence

  Baseline of Cycle 1 and Cycle 2, Day 14 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)

• Change From Baseline in Nonsense Mutation CFTR mRNA in Nasal Mucosa as Determined by Quantitative Polymerase Chain Reaction (PCR) Assay

  Baseline of Cycle 1 and Cycle 2, Day 14 and Day 28 of Cycle 1 and Cycle 2 (1 cycle=28 days)

• Change From Baseline in Number of Neutrophils in Blood

  Baseline Up to Day 56

Study Arms (1)

Ataluren

EXPERIMENTAL

Cycle 1: Within the first 28-day period, ataluren treatment will be taken 3 times per day with meals for 14 days at doses of 4 milligrams/kilogram (mg/kg) (breakfast), 4 mg/kg (lunch), and 8 mg/kg (dinner); there will then be an interval of 14 days without treatment. Cycle 2: Within the second 28-day period, ataluren treatment will be taken 3 times per day with meals for 14 days at doses of 10 mg/kg (breakfast), 10 mg/kg (lunch), and 20 mg/kg (dinner); there will then be an interval of 14 days without treatment.

Drug: Ataluren

Interventions

Ataluren DRUG

Ataluren will be provided as a vanilla-flavored powder to be mixed with water.

Also known as: PTC124

Ataluren

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CF based on documented evidence of a conclusively abnormal sweat test (sweat chloride \>60 milliequivalents/litre \[mEq/liter\]).
• Abnormal chloride secretion as measured by TEPD (a less than -5 mV TEPD assessment of chloride secretion with chloride-free amiloride and isoproterenol).
• Presence of a nonsense mutation in one of the alleles of the CFTR gene.
• Age ≥18 years.
• Body weight ≥40 kg.
• Forced expiratory volume in 1 second (FEV1) ≥40% of predicted for age, gender, and height (Knudson standards).
• Oxygen saturation (as measured by pulse oximetry) ≥92% on room air.
• Willingness of male and female participants, if not surgically sterile, to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and follow-up periods.
• Negative pregnancy test (for females of childbearing potential).
• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, and study restrictions.
• Ability to provide written informed consent.

You may not qualify if:

• Prior or ongoing medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
• Ongoing acute illness including acute upper or lower respiratory infections within 2 weeks before start of study treatment.
• History of major complications of lung disease within 2 months prior to start of study treatment.
• Abnormalities on screening chest x-ray suggesting clinically significant active pulmonary disease other than CF, or new, significant abnormalities that may be indicative of clinically significant active pulmonary involvement secondary to CF.
• Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test.
• Hemoglobin \<10 grams per deciliter (g/dL).
• Serum albumin \<2.5 g/dL.
• Abnormal liver function (serum alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma-glutamyl transferase \[GGT\], alkaline phosphatase, lactate dehydrogenase \[LDH\], or total bilirubin \> upper limit of normal).
• Abnormal renal function (serum creatinine \>1.5 times upper limit of normal).
• Pregnancy or breast-feeding.
• History of solid organ or hematological transplantation.
• Exposure to another investigational drug within 14 days prior to start of study treatment.
• Ongoing participation in any other therapeutic clinical trial.
• Ongoing use of thiazolidinedione peroxisome proliferator-activated receptor gamma (PPAR γ) agonists, eg, rosiglitazone (Avandia® or equivalent) or pioglitazone (Actos® or equivalent)
• Change in intranasal medications (including use of corticosteroids, cromolyn, ipratropium bromide, phenylephrine, or oxymetazoline) within 14 days prior to start of study treatment.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (1)

Hadassah University Hospital - Mount Scopus

Jerusalem, 91240, Israel

Location

Related Publications (1)

• Kerem E, Hirawat S, Armoni S, Yaakov Y, Shoseyov D, Cohen M, Nissim-Rafinia M, Blau H, Rivlin J, Aviram M, Elfring GL, Northcutt VJ, Miller LL, Kerem B, Wilschanski M. Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial. Lancet. 2008 Aug 30;372(9640):719-27. doi: 10.1016/S0140-6736(08)61168-X. Epub 2008 Aug 20.

  PMID: 18722008 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ataluren

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Eiten Kerem, MD

  Hadassah University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2005
• First Posted: October 12, 2005
• Study Start: November 30, 2005
• Primary Completion: May 31, 2006
• Study Completion: May 31, 2006
• Last Updated: June 11, 2020

Record last verified: 2020-06

Locations

IL (1)