PTC124 for the Treatment of Cystic Fibrosis

NCT00351078 | Completed Phase 2

• 1 other identifier: PTC124-GD-005e-CF
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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. In an ongoing Phase 2a study being performed at the Hadassah University Hospital - Mount Scopus in Israel, patients with nonsense-mutation-mediated CF have received PTC124 in two 14-day treatment courses. Preliminary results from that study indicate that PTC124 has pharmacodynamic activity of PTC124 in CF and that PTC124 can be safely administered in this patient population. This Phase 2b extension study is designed to evaluate the activity and safety of 3 months (approximately 84 days) of continuous treatment with PTC124 in the same patients who were enrolled to the Phase 2a study. The main purpose of this study is to understand whether PTC124 can be safely administered and achieve pharmacodynamic activity in patients with CF due to a nonsense mutation.

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis; Nonsense mutation; Premature stop codon; CF; PTC124

Outcome Measures

Primary Outcomes (1)

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

  84 days

Secondary Outcomes (9)

• Side effects

  84 days

• Presence of CFTR protein and mRNA

  84 days

• Compliance with treatment

  84 days

• Lung function

  84 days

• Sputum test

  84 days

Study Arms (1)

PTC124 PO

EXPERIMENTAL

4-, 4-, and 8-mg/kg TID first 14 days of cycle 10-, 10-, and 20-mg/kg TID second 14 days of cycle 28 day study

Drug: PTC124

Interventions

PTC124 DRUG

4-,4-, and 8-mg/kg PO first 14 days 10-, 10-, and 20-mg/kg TID second 14 days

PTC124 PO

Eligibility Criteria

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

You may qualify if:

• Patients must meet all of the following conditions to be eligible for enrollment into the study:
• Completion of ≥ 1 cycle of PTC124 treatment in the previous Phase 2a study protocol (Protocol Number PTC124-GD-005-CF).
• Abnormal nasal epithelial TEPD total chloride conductance (a more electrically negative value than -5 mV for Δchloride-free+isoproterenol).
• FEV1 ≥ 40% of predicted for age, gender, and height.
• 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.
• Evidence of signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial.

You may not qualify if:

• The presence of any of the following conditions will exclude a patient from enrollment in the study:
• 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 in this study.
• History of major complications of lung disease (including recent massive hemoptysis or pneumothorax) within 2 months prior to start of study treatment in this study.
• Abnormalities on screening chest x-ray suggesting clinically significant active pulmonary disease other than CF, or new, significant abnormalities such as atelectasis or pleural effusion which may be indicative of clinically significant active pulmonary involvement secondary to CF.
• Hemoglobin \<10 g/dL.
• Serum albumin \<2.5 g/dL.
• Abnormal liver function (serum total bilirubin \> the upper limit of normal, or serum ALT, AST, or GGT \>2.0 times the 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 in this study.
• 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 7 days prior to start of study treatment in this study.
• Change in treatment with systemic or inhaled corticosteroids within 7 days prior to start of study treatment in this study.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (1)

Hadassah University Hospital - Mount Scopus

Jerusalem, 91240, Israel

Location

Related Publications (1)

• Wilschanski M, Miller LL, Shoseyov D, Blau H, Rivlin J, Aviram M, Cohen M, Armoni S, Yaakov Y, Pugatsch T, Cohen-Cymberknoh M, Miller NL, Reha A, Northcutt VJ, Hirawat S, Donnelly K, Elfring GL, Ajayi T, Kerem E. Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis. Eur Respir J. 2011 Jul;38(1):59-69. doi: 10.1183/09031936.00120910. Epub 2011 Jan 13.

  PMID: 21233271 DERIVED

Related Links

• Provides description of the PTC124 study from which the patients will be enrolled into this study.

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

• Eitan Kerem, MD

  Hadassah University Hospital - Mount Scopus

  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: July 11, 2006
• First Posted: July 12, 2006
• Study Start: December 1, 2006
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: December 13, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)