To determine the effect of FP-025 vs placebo on the allergen (HDM)-induced late asthmatic response expressed as FEV1 AUC3-8h in subjects with clinically stable, mild allergic asthma and blood eosinophilia.
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Spirometry:
• Area under the time-FEV1 response curve from 3 to 8 hours post-allergen (FEV1
AUC3-8h)
Secondary outcome
- Pharmacodynamic endpoints include the effect of study treatments on allergen
(HDM)-induced changes in:
LAR expressed as max% fall in FEV1 from post-diluent baseline;
Early asthmatic response (EAR) expressed as FEV1 AUC0-3h;
EAR expressed as max% fall in FEV1 from post-diluent baseline;
Joint HDM-induced airway response expressed as AUC0-8h;
Airway hyperresponsiveness expressed as PC20FEV1(Meth) or PC20FEV1(Hist) (Day
10-Day 12);
Small airway parameters following HDM-challenge (i.e. R5, R20, R5-R20, AX, X5,
Fres);
Fractionated nitric oxide (FeNO);
Blood eosinophils.
- Potential treatment effect (FP-025 versus placebo) on baseline parameters
(i.e. Day 1 versus Day 10), including:
Blood eosinophils;
PC20FEV1(Meth) or PC20FEV1(Hist);
FeNO.
- Safety parameters include physical examination, clinical signs/symptoms
reporting (MedDRA), (S)AEs, vital signs, lung function measurements, overall
asthma symptoms, ECG and clinical safety laboratory outcomes (blood/urine).
- Pharmacokinetic parameters of FP-025 in blood (plasma) include Cmax, tmax,
and AUC0-tau
Background summary
FP-025 is a novel non-hydroxamate small molecule selective inhibitor of Matrix
Metalloproteinase 12 (MMP-12). It has 90-fold selectivity over the next closest
family member (MMP-2) and 2-3 orders of magnitude selectivity over the seven
other MMP family members (MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, and
MMP-14). MMP-12 has been shown to play an important role in several aspects of
chronic inflammatory airway diseases like asthma and COPD, including airway
inflammation, airway hyperresponsiveness, (small) airways remodeling and
disease severity [2-8]. In addition, FP-025 attenuated allergic inflammation
and improved lung function in two murine models of allergic inflammation (OVA
and HDM models) and even showed normalization of lung histology in the HDM
model.
Study objective
To determine the effect of FP-025 vs placebo on the allergen (HDM)-induced late
asthmatic response expressed as FEV1 AUC3-8h in subjects with clinically
stable, mild allergic asthma and blood eosinophilia.
Study design
This is a randomized, placebo-controlled, double-blind, 2-way cross-over,
2-centre study in male and female subjects with stable, mild HDM-allergic
asthma.
Intervention
Subjects will receive 400 mg FP-025 (8x 50 mg capsules, BID) and matching
placebo (8 capsules, BID) from Day 1 (evening = first dose) to Day 12 (morning
= last dose); a total of 22 doses per study period.
Study burden and risks
The dosage levels of the study drug are based on a previous clinical trial
conducted by the sponsor. The risk to health at the chosen dose is limited, but
the patients may experience any of the side effects in the ICF or symptoms that
have not been reported before. Volunteers health is closely monitored during
the study to minimize these risks. If the volunteers experience side effects,
the investigator will treat them where necessary. If new information is
available on the safety of the study medication, the volunteers are informed as
soon as possible. The blood collection procedure is not dangerous.
Sanchong Rd 3F., No. 19-3
Taipei 115
TW
Sanchong Rd 3F., No. 19-3
Taipei 115
TW
Listed location countries
Age
Inclusion criteria
1. Females or males, between 18 and 55 years of age at Screening, inclusive, on
the day of signing the Informed Consent Form (ICF).
2. Apart from a clinically stable asthma and HDM-allergy, subjects should be
generally healthy with no history of a clinically relevant medical condition
that in the opinion of the investigator might interfere with successful study
conduct and no clinically relevant abnormalities on medical history, physical
exam, vital signs, laboratory parameters or ECG at Screening.
3. Subject has a BMI >= 18.0 kg/m2 and <= 32.0 kg/m2 (and weighs >=50 kg).
4. Subjects have been diagnosed with asthma cf GINA guidelines.
5. Subjects should have established allergy for HDM (serum HDM-specific IgE or
positive SPT at Screening or documented within 1 year pre-screening).
6. No severe exacerbation of asthma within past 1 year requiring hospital
admission and/or treatment with oral corticosteroids; no (never) intensive care
admissions for asthma or intubation).
7. FEV1 should be >=70% of predicted on Screening Day 2.
8. On Screening Day 2, PC20FEV1(Meth) should be <16 mg/mL if methacholine
chloride is used (or adjusted by a factor of 1.2 if methacholine bromide is
used). If histamine is used, PC20FEV1(Hist) should be <16 mg/mL.
9. Baseline blood eosinophils should be >=150 cells/µL at Screening or
documented within 3 months before Screening Day 1.
10. Subjects should have a documented airway late response to inhaled HDM on
Screening Day 3.
11. Subjects of childbearing potential must be willing to use adequate
contraception (double-barrier) or must refrain from intercourse.
12. Female subjects of non-childbearing potential must have had >= 12 months of
spontaneous amenorrhea (with follicle-stimulating hormone [FSH] >= 30 mIU/mL).
Surgically sterile women are defined as those who have had a hysterectomy,
bilateral ovariectomy (for *benign* reasons), or bilateral tubal ligation.
13. All female subjects should have a negative pregnancy test at Screening and
on Day -1.
14. Negative alcohol breath test on Screening Day 1 and Day -1.
15. Negative cotinine test on Screening Day 1 and Day -1.
16. Negative urine drug screen for recreational and other drugs on Screening
Day 1 and Day -1.
17. Subjects are non-smokers. A non-smoker is defined as an individual who has
abstained from smoking for at least 1 year prior to Screening Day 1. Number of
years smoked x number of packs per day should be <5 pack years.
18. Subject should be willing and able to perform the lung function tests and
other study-related procedures and comply with study protocol requirements.
19. Subject should provide a signed and dated informed consent.
Exclusion criteria
1. Subject has any active and/or chronic (physical or mental) condition
requiring maintenance (pharmaco)therapy or which otherwise precludes subject
from safe or adequate study participation (ineligibility will be assessed by
the PI).
2. Subject has a history of cancer (exception: localized basalioma or cervix
carcinoma in situ).
3. Subject had any major (nasal) surgery in the 6 months before Screening Day 1.
4. Subject is pregnant or lactating.
5. Subject is using immunotherapy that according to the PI may interfere with
the study (e.g. in case of immunotherapy with HDM or when subject is in the
updosing phase of any immunotherapy).
6. Subject regularly used alcohol (intake of >21 units/wk for males and >14
units/wk for females) and/or recreational drugs within the last 6 months prior
to screening.
7. Subject had any respiratory (viral) infections (e.g. common cold) within 3
weeks of Screening Day 1 or on Day -1.
8. Subject is using maintenance asthma therapy or long-acting bronchodilators
or any other anti-asthma or anti-allergic medications (as detailed in the
protocol) other than infrequent use of SABA prn only.
9. Subject is using prohibited medications as detailed in the protocol.
10. Multi-sensitized symptomatic subjects with seasonal (pollen) allergies
should be included outside of the relevant allergen season and/or should not be
in frequent contact with the relevant allergen during the study.
11. Subject has any known allergic response for the medications used or known
severe allergic reactions or anaphylaxis (to food/medications/insect venoms).
12. Subject participated in medical studies in the past 3 months
(non-biologicals) or in the past 6 months (biologicals).
13. Subject is anticipated not to comply with study medication or other aspects
of the study (at the discretion of the investigator).
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 | EUCTR2017-005164-17-NL |
| CCMO | NL64799.056.18 |