PTC124 for Cystic Fibrosis

NCT00234663 | Completed Phase 2

• 2 other identifiers: PTC124-GD-003-CF1R01FD003009-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

In some patients 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. PTC124 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 PTC124 can safely increase functional CFTR protein in the cells of patients with CF due to a nonsense mutation.

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis; Nonsense mutation; Premature stop codon

Outcome Measures

Primary Outcomes (1)

• CFTR activity as assessed by nasal transepithelial potential difference (TEPD)

Secondary Outcomes (5)

• Side effects

• Presence of CFTR protein and mRNA

• Compliance with treatment

• Lung function

• PTC124 pharmacokinetics

Interventions

PTC124 DRUG

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 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.
• 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 patients, 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 patient, 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 g/dL.
• Serum albumin \<2.5 g/dL.
• Abnormal liver function (serum ALT, AST, GGT, alkaline phosphatase, 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
• Cystic Fibrosis Foundation: collaborator
• FDA Office of Orphan Products Development: collaborator

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35233-1711, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304-5786, United States

Location

The Children's Hospital

Denver, Colorado, 80218, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

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

• John P Clancy, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 5, 2005
• First Posted: October 7, 2005
• Study Start: September 1, 2005
• Primary Completion: August 1, 2006
• Study Completion: August 1, 2006
• Last Updated: January 13, 2009

Record last verified: 2009-01

Locations

US (5)