Cystic FibrosisPhase 2NCT00351078
PTC124 for the Treatment of Cystic Fibrosis
A Phase 2 study testing PTC124 in people with Cystic Fibrosis, run by PTC Therapeutics at 1 site in Israel.
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
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteIsrael
- Study dates
- Dec 2006to Jul 2007
- 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
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Use of or requirement for inhaled gentamicin or amikacin within 14 days prior to start of study treatment in this study or during study treatment.
- Requirement for systemic aminoglycoside antibiotics within 14 days prior to start of study treatment in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2b Extension 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. 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.
Read the detailed description
In this study, the same patients who were enrolled in a previous study of PTC124 (protocol number PTC124-GD-005-CF) will be treated with the investigational drug PTC124 for a period of 84 days. 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 be assigned to receive PTC124 treatment (based upon TEPD results from the previous study) at 1 of the 2 following dose levels:
- PTC124, given 3 times per day (TID) with a regimen of 4 mg/kg at breakfast, 4 mg/kg at lunch, and 8 mg/kg at dinner, or
- PTC124, given 3 times per day (TID) with a regimen of 10 mg/kg at breakfast, 10 mg/kg at lunch and 20 mg/kg at dinner.
During the study, PTC124 efficacy, safety, and pharmacokinetics will be evaluated periodically with measurement of transepithelial potential difference (TEPD), medical history, physical examinations, blood tests, urinalysis, sputum tests, ECGs, chest x-ray, and pulmonary function tests.
- Conditions
- Cystic Fibrosis
- Being tested
- PTC124
- Keywords
- Cystic fibrosis, Nonsense mutation, Premature stop codon, CF, PTC124
- 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
4-,4-, and 8-mg/kg PO first 14 days 10-, 10-, and 20-mg/kg TID second 14 days
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: PTC124 |
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)
Measured: 84 days
Secondary outcomes (9)
Side effects
Measured: 84 days
Presence of CFTR protein and mRNA
Measured: 84 days
Compliance with treatment
Measured: 84 days
Lung function
Measured: 84 days
Sputum test
Measured: 84 days
PTC124 pharmacokinetics
Measured: 84 days'
Changes in CF symptoms
Measured: 84 days
Changes in weight
Measured: 84 days
Changes in cough
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2006 (estimated)
- Study startDec 2006
- Primary completionJul 2007
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eitan Kerem, MD, Principal investigator, Hadassah University Hospital - Mount Scopus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00351078
- Sponsor's protocol ID
- PTC124-GD-005e-CF
- Status last verified
- Apr 2017
- First submitted
- 11 Jul 2006
- Last updated
- 13 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 21233271
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b Extension Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00351078
- Acronym / sponsor ID
- PTC124-GD-005e-CF
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic fibrosis, Nonsense mutation, Premature stop codon, CF, PTC124
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 12 Jul 2006 (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. 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.
Detailed description
In this study, the same patients who were enrolled in a previous study of PTC124 (protocol number PTC124-GD-005-CF) will be treated with the investigational drug PTC124 for a period of 84 days. 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 be assigned to receive PTC124 treatment (based upon TEPD results from the previous study) at 1 of the 2 following dose levels:
- PTC124, given 3 times per day (TID) with a regimen of 4 mg/kg at breakfast, 4 mg/kg at lunch, and 8 mg/kg at dinner, or
- PTC124, given 3 times per day (TID) with a regimen of 10 mg/kg at breakfast, 10 mg/kg at lunch and 20 mg/kg at dinner.
During the study, PTC124 efficacy, safety, and pharmacokinetics will be evaluated periodically with measurement of transepithelial potential difference (TEPD), medical history, physical examinations, blood tests, urinalysis, sputum tests, ECGs, chest x-ray, and pulmonary function tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PTC124 PO | Experimental | Drug: PTC1244-, 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
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 |
|---|---|---|
| PTC1244-,4-, and 8-mg/kg PO first 14 days 10-, 10-, and 20-mg/kg TID second 14 days | Drug | PTC124 PO |
Primary outcome
CFTR activity as assessed by nasal transepithelial potential difference (TEPD)
Time frame: 84 days
9 secondary outcomes
Side effects
Time frame: 84 days
Presence of CFTR protein and mRNA
Time frame: 84 days
Compliance with treatment
Time frame: 84 days
Lung function
Time frame: 84 days
Sputum test
Time frame: 84 days
PTC124 pharmacokinetics
Time frame: 84 days'
Changes in CF symptoms
Time frame: 84 days
Changes in weight
Time frame: 84 days
Changes in cough
Time frame: 84 days
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 Dec 2017.
- Derived from this study: PubMed 21233271Wilschanski 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.
- Provides description of the PTC124 study from which the patients will be enrolled into this study.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Eitan Kerem, MD principal investigator
Hadassah University Hospital - Mount Scopus
1 site 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 1 site in Israel.
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 10 inclusion and 17 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 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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) (time frame: 84 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00351078, which also lists 1 linked publication.
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 Dec 2017.