The primary objective is to evaluate safety and tolerability of treatment with AP01.This study will also evaluate the effect of AP01 on various efficacy measures as follows:* To evaluate the safety and tolerability of treatment with AP01 when given…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Treatment-emergent AEs
* Change from pre-dose to post-dose FEV1 after initial dose
* Treatment-emergent deaths
* Treatment-emergent changes in clinical laboratory findings
* Changes in vital signs
Secondary outcome
* Change from Baseline in FVC % predicted
* Change from Baseline in DLCO
* Change from Baseline in Patient Reported Outcomes (PRO)
* Change from Baseline in cough frequency and intensity
* Change from Baseline in extent of fibrosis and lung volumes
Background summary
Idiopathic pulmonary fibrosis (IPF) is a type of lung disease that results in
scarring (fibrosis) of the lungs for an unknown reason. Over time, the scarring
gets worse and it becomes hard to take in a deep breath and the lungs cannot
take in enough oxygen.
Momentarily the study drug (pirfenidone solution for inhalation) is available
as treatment for idiopathic pulmonary fibrosis, which is given in a capsule for
oral use. However, studies have shown the use of oral pirfenidone leads to side
effects in many patients and in some cases these side effects prevent the use
of medication. A previous study has shown that a single dose of AP01 up to 100
mg given as an inhaled formulation was safe and well tolerated. It has shown
that more pirfenidone was absorbed in the lungs which may lead to better
efficacy as well as a reduction in the level of study drug which was absorbed
by the blood which causes less side effects.
In this study we want to test the safety and tolerability of multiple doses.
The results of this study will also be used for future research.
Study objective
The primary objective is to evaluate safety and tolerability of treatment with
AP01.
This study will also evaluate the effect of AP01 on various efficacy measures
as follows:
* To evaluate the safety and tolerability of treatment with AP01 when given
either once or twice daily to patients with IPF;
* To estimate the treatment effect of AP01 given 50 mg once daily and 100 mg
twice daily on absolute change in percent predicted FVC in patients
with IPF;
* To estimate the treatment effect of AP01 given 50 mg once daily and 100 mg
twice daily on absolute change in percent predicted Diffusion
Capacity for Carbon Monoxide (DLCO) in patients with IPF;
* To compare the safety and efficacy of 50 mg once daily vs 100 mg twice daily
dosing to provide guidance on dosing regimens for future studies;
* To estimate the treatment effect of AP01 given 50 mg once daily and 100 mg
twice daily on change in Patient Reported Outcomes (PROs) and
cough in patients with IPF;
Study design
This is a randomized, open-label study of Pirfenidone Solution for Inhalation
(AP01) 50 mg once daily or 100 mg twice daily. This study has 2 parts.
Part A (24 weeks): Patients will be randomised in a 1:1 ratio to one of two
treatment arms: 50 mg once daily or 100 mg twice daily. On Day 1, the initial
dose of the drug will be administered in the clinic to confirm airway
tolerance. If in the investigator*s opinion, the patient had tolerability
issues during the first dose administration, a second dose, at least 4 hours
later, will also be observed. The remainder of the doses will be administered
by the patient outside of the clinic. Patients will have a telephone assessment
at Week 1 and an in-clinic assessment at Weeks 4, 8, 12, 16, 20, and 24.
Patients who do not continue to Part B or who are withdrawn from the study
prior to completion should return for an Early Termination visit. Week 4 safety
data from the first 20 patients will be reviewed by a Data and Safety
Monitoring Board (DSMB), who may suggest changes to design or stopping of the
study based on safety concerns.
Part B (48 weeks): Patients who, in the opinion of the investigator, are
compliant with study treatment dosing and study procedures will be permitted to
enter Part B. All patients will continue to receive the treatment regimen (50
mg once daily or 100 mg twice daily) to which they were randomized in Part A.
If one dosing regimen is determined to be superior either from an efficacy or
safety standpoint, Part B may be converted to a single dose regimen. All
patients who participate in Part B will be dosed with the selected regimen. Any
patients already participating in Part B will be converted to the chosen single
dose regimen at that time. Patients will have monthly telephone assessments and
quarterly in-clinic assessments. All patients that complete the study visits
through Part B will return for a Follow-up visit, 28 days after their End of
Study visit.
Intervention
The research is divided into part A and part B. Part A lasts 24 weeks
(approximately 6 months). Part B lasts 48 weeks (about 1 year).
Patients will be assigned to one of the following treatments:
* 50 mg AP01 once daily;
* 100 mg AP01 twice daily (at least 4 hours apart).
Study burden and risks
Please refer to table 5 and 6 in the protocol, page 40-42 (schedule of tests
and events) for more information.
The research is divided into two parts, part A and B.
Part A lasts for 24 weeks (about 6 months). Patients are asked to come to the
hospital every four weeks during this period.
Part B lasts 48 weeks (about 1 year). In this period, patients are asked to
come to the hospital every 12 weeks and are contacted by telephone every month.
The first two visits (screening and visit 2) last about 3-4 hours. all other
visits take about 1-2.5 hours.
During these visits the following tests and procedures will take place:
- Demographic and medical history (1 time)
- Physical exam, vital signs (13 times)
- ECG (1 time)
- CT scans of the Lungs (2 times)
- Questionnaires: Cough VAS, KBILD and LCQ (12 times)
- Blood and urine tests (13 times)
- Spirometry tests (including diffusing capacity (DLCO) test (5 extra
times for this research)
- Patient will be asked to wear a Cough monitor for 24 hours and to
complete a diary during this time (3 times during this study)
- Pregnancy tests in women of childbearing potential (12 times)
- Female patients: no breastfeeding allowed. Effective methods of birth control
must be used from the time of signing the ICF, throughout the
entire study and for 30 days following the last dose of the study drug.
Possible known side effects have been described in the IB, patient informed
consent form and section E9 of this form.
Momentarily the study drug (pirfenidone) is available as treatment for
idiopathic pulmonary fibrosis, which is given in a capsule for oral use.
However, studies have shown the use of oral pirfenidone leads to side effects
in many patients and in some cases these side effects prevent the use of
medication. A previous study has shown that a single dose up to 100 mg/mL given
as an inhaled formulation was safe and well tolerated. Inhalation provides
higher levels of drug to the lungs and lower levels to the blood, which may
improve efficacy and reduce side effects.
In this study we want to test the safety and tolerability of multiple doses.
The results of this study will also be used for future research.
Pike Street, Suite 1500 701
Seattle, WA 98101
US
Pike Street, Suite 1500 701
Seattle, WA 98101
US
Listed location countries
Age
Inclusion criteria
1. Male and female patients, at least 40 years of age at Screening
2. Not eligible for oral pirfenidone and nintedanib due to national formulary;
restrictions OR intolerant to or unwilling to start oral pirfenidone and
nintedanib, if previously offered;
3. Clinical symptoms consistent with IPF of * 12 months duration (with or
without IPF diagnosis)
4. Diagnosis of IPF, defined as the first instance in which a patient was
informed of having IPF, no more than 60 months before randomization;
Patients that have had an IPF diagnosis * 1 year, the following criteria must
be met:
- HRCT and/or Surgical Lung Biopsy findings consistent with UIP. If
honeycombing is not present on the HRCT, then one or both of the following
criteria must be present:
* Disease progression since diagnosis by HRCT and/or
* An absolute loss of FVC * 5% percent predicted over the past 12 months,
Patients that have had IPF diagnosis within the last year, the following
criteria must be met:
- Diagnosis of Usual Interstitial Pneumonia (UIP) or IPF by HRCT (HRCT must be
performed within 12 months prior to Screening) and/or Surgical Lung Biopsy
5. Extent of fibrotic changes (honeycombing, reticular changes) greater than
the extent of emphysema on HRCT scan, confirmed by central review;
6. No features supporting an alternative diagnosis on transbronchial biopsy,
BAL, or surgical lung biopsy, if performed;
7. 40% * FVC * 90 % predicted at Screening based on Global Lung Initiative12
equations. The first 20 patients randomized must have FVC * 50% predicted.
After the first 20 patients have randomized, patients with FVC 40% - 50%
predicted will be allowed to be randomized in the
study but randomization for these patients will be capped at 20;
8. Change in FVC (measured in liters) between Screening and Day 1 (pre-dose
measurement) must be a < 10% relative difference;
9. 30 * % DLCO * 90% at Screening;
10. In the investigator's opinion, no evidence of improvement in measure of IPF
disease severity over the preceding year;
11. FEV1/FVC * 70%;
12. Able to understand and sign a written informed consent form;
13. Able to understand the importance of adherence to study treatment and the
study protocol and willing to follow all study requirements, including the
concomitant medication restrictions, throughout the study;
Exclusion criteria
1. Significant clinical worsening of IPF between Screening and Day 1, in the
opinion of the investigator;
2. Not a suitable candidate for enrollment or unlikely to comply with the
requirements of this study, in the opinion of the investigator;
3. History of acute IPF exacerbation requiring hospitalization in the last3
months;
4. History of clinically significant environmental exposure known to cause
pulmonary fibrosis, including but not limited to drugs (such as amiodarone),
asbestos, beryllium, radiation, and domestic birds;
5. Known explanation for interstitial lung disease, including but not limited
to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis,
bronchiolitis obliterans organizing pneumonia, human
immunodeficiency virus, viral hepatitis, and cancer;
6. Clinical diagnosis of any connective tissue disease, including but not
limited to scleroderma, polymyositis/dermatomyositis, systemic lupus
erythematosus, and rheumatoid arthritis;
7. Current diagnosis of asthma or chronic obstructive pulmonary disease;
8. Clinical evidence of active infection, including but not limited to
bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis;
9. Females with a positive pregnancy test at Screening or are currently
breastfeeding
10. Any history of malignancy likely to result in significant disability or
likely to require significant medical or surgical intervention within the next
6 months. This does not include minor surgical procedures for
localized cancer (e.g., basal cell carcinoma);
11. Any condition other than IPF that, in the opinion of the investigator, is
likely to result in the death of the patient within the next 6 months;
12. History of severe hepatic impairment or end-stage liver disease or ALT or
AST greater than 5 times the upper limit of normal at Screening;
13. History of end-stage renal disease requiring dialysis
14. Participation in a clinical study with administration of an investigational
drug product within the previous 30 days, or five half-lives of the previously
administered investigational product.
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 |
|---|---|
| Other | ACTRN12618001838202p |
| EudraCT | EUCTR2018-003388-75-NL |
| CCMO | NL68352.100.18 |