To evaluate the ability of ataluren to improve pulmonary function relative to placeboTo determine the effect of ataluren on:1. Pulmonary symptoms2. General well-being3. Health-related Quality Life (HRQL)
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Absolute change in %-predicted FEV1 at week 48, defined as the average between
the change at week 40 and that at week 48 (by spirometry).
Secondary outcome
1. Rate of pulmonary exacerbations (expanded Fuchs criteria)
2. Change from baseline in Body Mass Index (BMI)
3. Respiratory HRQL as assessed by the Cystic Fibrosis Questionnaire - Revised
(CFQ-R) respiratory domain
Background summary
There are no approved systemic therapies that address the underlying cause of
CF caused by other mutations, such as premature
stop codons. New agents are therefore needed that can overcome the fundamental
genetic defect
by restoring CFTR production and function.
Study objective
To evaluate the ability of ataluren to improve pulmonary function relative to
placebo
To determine the effect of ataluren on:
1. Pulmonary symptoms
2. General well-being
3. Health-related Quality Life (HRQL)
Study design
It is planned that the study will enroll ~208 subjects (~184 fully evaluable)
with nonsensemutation-
mediated CF who are *6 years of age and have an FEV1 *40% and *90% of predicted.
Subjects will be stratified based on age, inhaled antibiotic use, and baseline
FEV1, and will be
randomized in a 1:1 ratio to receive oral ataluren administered 3 times per day
(TID) at respective
morning, midday, and evening doses of 10-, 10-, and 20-mg/kg or placebo. Based
on the results of
a previously conducted study, patients treated with chronic inhaled
aminoglycosides (including
TOBI) will not be eligible for participation [Rowe 2012]. Spirometry
measurement at the
screening visit will establish patient eligibility for inclusion based on lung
function. FEV1 stability
will be assessed during the approximately 4-week screening period at the
conclusion of which
patients will be required to demonstrate a relative change in %-predicted FEV1
of less than 15%
when compared to the screening value. Assessments will be performed every ~8
weeks, depending
upon the outcome measure.
At the completion of blinded treatment, all compliant participants will be
eligible to receive openlabel
ataluren in a separate extension study, at the same 10-, 10-, 20-mg/kg dose
level.
Intervention
Dosing of study drug will be based on milligrams of drug per kilogram of
subject body weight at randomization and will be calculated to allow for dosing
with 1 or 2 of the 3 available sachet dose strengths (125- or 250- or 1000-mg
of active drug or matching placebo).
Study burden and risks
In previous studies with ataluren adults and children with CF, the common
symptoms included:
* In at least 20% of subjects: pulmonary exacerbation, cough
* Between 10% and 20% of subjects: viral upper respiratory tract infection,
headache, fever (pyrexia), abdominal pain, sinusitis, vomiting, diarrhea
* In 5% to 10% of subjects: runny nose (rhinitis), productive cough, coughing
blood (hemoptysis), nausea, upper abdominal pain, fatigue, common cold
(nasopharyngitis), abnormal loss of weight, back pain, constipation, crackling
in lungs (rales).
Corporate Court 100
South Plainfield, NJ 07080
US
Corporate Court 100
South Plainfield, NJ 07080
US
Listed location countries
Age
Inclusion criteria
indicating that the subject (and/or his parent/legal guardian) has been
informed of all pertinent aspects of the trial.
2. Age *6 years.
3. Body weight *16 kg.
4. Sweat chloride >60 mEq/L.
5. Documentation of the presence of a nonsense mutation in at least 1
allele of the CFTR gene, as determined by genotyping performed at a
laboratory certified by the College of American Pathologists (CAP), or
under the Clinical Laboratory Improvement Act/Amendment (CLIA), or
by an equivalent organization.
6. Verification that a blood sample has been drawn for sequencing of the
CFTR gene.
7. Ability to perform a valid, reproducible spirometry test using the
study-specific spirometer with demonstration of an FEV1 *40% and *
90% of predicted for age, gender, and height.
8. Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening %-predicted FEV1 value.
9. Resting oxygen saturation (as measured by pulse oximetry) *92% on
room air.
10. Confirmed screening laboratory values within the central laboratory
ranges specified in Table 2 of the protocol.
11. In subjects who are sexually active, willingness to abstain from
sexual intercourse or employ a barrier or medical method of
contraception during the study drug administration and 60-day follow-up
period.
12. Willingness and ability to comply with all study procedures and
assessments, including scheduled visits, drug administration plan, study
procedures, laboratory tests, and study restrictions.
Exclusion criteria
1. Known hypersensitivity to any of the ingredients or excipients of the
study drug (polydextrose, polyethylene glycol 3350, poloxamer 407,
mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla,
colloidal silica, or magnesium stearate).
2. Previous participation in the Phase 3 trial of ataluren (PTC124-GD-
009-CF).
3. Any change (initiation, change in type of drug, dose modification,
schedule modification, interruption, discontinuation, or re-initiation) in a
chronic treatment/prophylaxis regimen for CF or for CF-related
conditions within 4 weeks prior to screening or any change in acute therapy between screening and randomization.
4. Chronic use of inhaled or systemic tobramycin within 4 weeks to screening.
5. Exposure to another investigational drug within 4 weeks prior to
screening.
6. Ongoing participation in any other therapeutic clinical trial.
7. Evidence of pulmonary exacerbation or acute upper or lower
respiratory tract infection (including viral illnesses) within 3 weeks prior
to screening, or between screening and randomization.
8. Treatment with intravenous antibiotics within 3 weeks prior to
screening.
9. Ongoing immunosuppressive therapy (other than corticosteroids).
10. Ongoing warfarin, phenytoin, or tolbutamide therapy.
11. History of solid organ or hematological transplantation.
12. Major complications of lung disease (including massive hemoptysis,
pneumothorax, or pleural effusion) within 8 weeks prior to screening.
13. Known portal hypertension.
14. Positive hepatitis B surface antigen, hepatitis C antibody test, or
human immunodeficiency virus (HIV) test.
15. Pregnancy or breast-feeding.
16. Current smoker or a smoking history of *10 pack-years (number of
cigarette packs/day × number of years smoked).
17. Prior or ongoing medical condition (eg, concomitant illness,
alcoholism, drug abuse, psychiatric condition), medical history, physical
findings, ECG findings, or laboratory abnormality that, in the
investigator's opinion, could adversely affect the safety of the subject,
makes it unlikely that the course of treatment or follow-up would be
completed, or could impair the assessment of study results.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004581-34-NL |
| CCMO | NL49005.091.14 |