Cystic FibrosisPhase 2NCT00234663
PTC124 for Cystic Fibrosis
A Phase 2 study testing PTC124 in people with Cystic Fibrosis, run by PTC Therapeutics at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- PTC124
- How many people
- 24 participants
- Where
- 5 sitesUnited States
- Study dates
- Sep 2005to Aug 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
- Change in treatment with systemic or inhaled corticosteroids within 14 days prior to start of study treatment.
- Use or requirement for inhaled gentamicin or amikacin within 14 days prior to start of study treatment or during study treatment.
- Requirement for systemic aminoglycoside antibiotics within 14 days prior to start of study treatment.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35233-1711
Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
The Children's Hospital
Denver, Colorado, 80218
Stanford University Medical Center
Palo Alto, California, 94304-5786
About this study
Official title: A Phase 2 Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis
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.
Read the detailed description
In this study, patients with CF due to a nonsense mutation will be treated with a new investigational drug called PTC124. Evaluation procedures (history, physical examination, blood and urine tests to assess organ function, electrocardiogram (ECG), chest x-ray, and CF-specific tests) to determine if a patient qualifies for the study will be performed within 21 days prior to the start of treatment. Eligible patients who elect to enroll in the study will then participate in two 28-day treatment and follow-up periods (56 days total). Within the first 28-day period, PTC124 treatment will be taken 3 times per day with meals for 14 days at doses of 4 mg/kg (breakfast), 4 mg/kg (lunch) and 8 mg/kg (dinner); there will then be an interval of 14 days without treatment. Within the second 28-day period, PTC124 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. There will be a 2-night stay at the clinical research center at the beginning and at the end of each 14 days of PTC124 treatment, which means that there will be four 2-night stays at the clinical research center during the study. During the study, PTC124 efficacy, safety, and pharmacokinetics will be evaluated periodically with measurement of transepithelial potential difference (TEPD), nasal mucosal brushing to assess for cellular CFTR mRNA and protein, medical history, physical examinations, blood tests, urinalysis, ECGs, chest x-ray, and pulmonary function tests.
- Conditions
- Cystic Fibrosis
- Being tested
- PTC124
- Keywords
- Cystic fibrosis, Nonsense mutation, Premature stop codon
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTC124Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2005 (estimated)
- Study startSep 2005
- Primary completionAug 2006
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cystic Fibrosis Foundation, FDA Office of Orphan Products Development
- Investigators
- John P Clancy, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00234663
- Sponsor's protocol ID
- PTC124-GD-003-CF
- Other IDs
- 1R01FD003009-01
- Status last verified
- Jan 2009
- First submitted
- 5 Oct 2005
- Last updated
- 13 Jan 2009
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00234663
- Acronym / sponsor ID
- PTC124-GD-003-CF
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic fibrosis, Nonsense mutation, Premature stop codon
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Cystic Fibrosis Foundation, FDA Office of Orphan Products Development
- Study start
- Sep 2005
- Primary completion
- Aug 2006 (actual)
- Study completion
- Aug 2006 (actual)
- First posted
- 7 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this study, patients with CF due to a nonsense mutation will be treated with a new investigational drug called PTC124. Evaluation procedures (history, physical examination, blood and urine tests to assess organ function, electrocardiogram (ECG), chest x-ray, and CF-specific tests) to determine if a patient qualifies for the study will be performed within 21 days prior to the start of treatment. Eligible patients who elect to enroll in the study will then participate in two 28-day treatment and follow-up periods (56 days total). Within the first 28-day period, PTC124 treatment will be taken 3 times per day with meals for 14 days at doses of 4 mg/kg (breakfast), 4 mg/kg (lunch) and 8 mg/kg (dinner); there will then be an interval of 14 days without treatment. Within the second 28-day period, PTC124 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. There will be a 2-night stay at the clinical research center at the beginning and at the end of each 14 days of PTC124 treatment, which means that there will be four 2-night stays at the clinical research center during the study. During the study, PTC124 efficacy, safety, and pharmacokinetics will be evaluated periodically with measurement of transepithelial potential difference (TEPD), nasal mucosal brushing to assess for cellular CFTR mRNA and protein, medical history, physical examinations, blood tests, urinalysis, ECGs, chest x-ray, and pulmonary function tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTC124 | Drug | – |
Primary outcome
CFTR activity as assessed by nasal transepithelial potential difference (TEPD)
5 secondary outcomes
Side effects
Presence of CFTR protein and mRNA
Compliance with treatment
Lung function
PTC124 pharmacokinetics
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John P Clancy, MD principal investigator
University of Alabama at Birmingham
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PTC124 in people with Cystic Fibrosis, run by PTC Therapeutics at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CFTR activity as assessed by nasal transepithelial potential difference (TEPD). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2009.