A study to look at the safety, tolerability and efficacy of repeated doses of different concentrations of the study drug during controlled inhalation of allergens in adult asthmatics.

• Register: EUCTR
• Last refreshed on: 13 May 2013
• Main ID: EUCTR2012-001483-29-GB
• Date of registration: 21/06/2012
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: A study to look at the safety, tolerability and efficacy of repeated doses of different concentrations of the study drug during controlled inhalation of allergens in adult asthmatics.
• Scientific title: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, THREE-WAY CROSSOVER STUDY TO EVALUATE THE EFFICACY AFTER ALLERGEN CHALLENGE, SAFETY, AND TOLERABILITY OF TWO DOSES OF INHALED CHF6001 DPI AFTER 9 DAYS OF TREATMENT IN ADULT PATIENTS WITH ASTHMA.
• Date of first enrolment: 08/08/2012
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001483-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

United Kingdom

Contacts

• Name: Sara Collarini
• Affiliation: Chiesi Farmaceutici S.p.A.

• Name: Sara Collarini
• Affiliation: Chiesi Farmaceutici S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1.Written informed consent (IC) prior to any studyrelated
procedures;
2.Non or exsmokers
3.Male or female aged between 18 and 60 years;
4.Body mass index between 18 and 32 kg/m2 inclusively;
5.A cooperative attitude and ability to be trained about the proper use of the Aerolizer® DPI and to perform spirometry;
6.Diagnosis of intermittent or persistent mild to moderate allergic asthma, steroidnaïve and generally in good health;
7.Predisposition to an allergic reaction (atopy) to at least one common
aeroallergen
8.At the time of randomisation, a confirmed “dualresponder”
having demonstrated both a late asthmatic response and an early asthmatic response.
9.Sputum producer cohort only: able to produce an adequate induced sputum sample,
10 hours after the allergen challenge at screening.
10.No regular antiasthmatic medication except salbutamol inhaler on an “as needed basis” starting from the first screening visit;
11.Willing to use an approved method of contraception from the time of dose administration and until 90 days after the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Worsening of asthma or a respiratory tract infection within 4 weeks of any screening procedure requiring a change in asthma therapy or is deemed clinically significant by the investigator;
2.History of lifethreatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures or hospitalisation (including emergency room visits) for the treatment of asthma within 3 months of any screening procedure, or have been hospitalized for asthma more than twice in last 12 months;
3.Pregnant or lactating women.
4.History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or lightheadedness;
5.History or symptoms of significant neurologic disease, including transient
ischemic attack (TIA), stroke, seizure disorder, or behavioural disturbances;
6.Symptomatic with hay fever at screening or predicted to have symptomatic hay fever during the study;
7.Unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; cardiovascular disease, uncontrolled gastrointestinal disease; neurological disease; uncontrolled haematological disease; uncontrolled autoimmune disorders, or other which may impact the feasibility of the results of the study.
8.Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical investigation;
9.History of serious adverse reaction, severe hypersensitivity or allergy to any drug or in any other circumstance (e.g. anaphylaxis);
10.Use of systemic corticosteroids, nebulised bronchodilators, oral beta2agonists 6 weeks prior to study entry;
11.Use of leukotrienes modifiers, roflumilast, cromoglycate 4 weeks prior to study entry;
12.Use of long acting 2agonists and/or inhaled corticosteroids (ICS) within 6 months prior to study entry;
13.Use of short or longacting nonsedative
antihistamines within 2 or 7 days, respectively, prior to screening until the end of the study;
14.Chronic use of any other medication for treatment of allergic lung disease other than shortacting bronchodilators taken as needed during the study;
15.Receipt of an investigational drug treatment within the preceding 30 days, or a longer and more appropriate time as determined by the Investigator
16.Blood draws of 250 millilitres (mL) or more within 45 days prior to enrolment in the study;
17.Ongoing use of tobacco products or previous usage within the past 12 months or past history greater than or equal to 5 packyears.
18.Lung disease other than intermittent or mild to moderate allergic asthma;
19.Recent (less than 1 year) history of alcohol dependency;
20.Unwillingness or inability to comply with the study protocol for any other reason;


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

asthma
MedDRA version: 14.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Code: CHF6001 DPI
Pharmaceutical Form: Inhalation powder, hard capsule
Current Sponsor code: CHF6001 DPI
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: To determine the effect of CHF6001 DPI in attenuating the late asthmatic response (LAR) after an allergen challenge (AC) following 9 days of inhaled dosing in adult patients with allergic asthma.

Secondary Objective: • To determine the effect of CHF6001 DPI in attenuating the early asthmatic response (EAR) after an allergen challenge,
• To assess the responsiveness to a methacholine (MCh) challenge 24 hours after an allergen challenge,
• To assess the allergen induced changes in sputum eosinophils, neutrophils and mediators (Eosinophilic cationic protein (ECP), neutrophil elastase (NE), Interleukin-5 (IL-5), IL-8, Eotaxin) 10 hours after an allergen challenge,
• To assess safety and tolerability,
• To measure systemic exposure to CHF6001 and its metabolites CHF5956 and CHF 6095

Primary end point(s): Late asthmatic response (LAR), defined as the weighted AUC of the FEV1 percent change from post-diluent value from 4 to 10 hours post-allergen challenge (FEV1 AUC0-4h)

Timepoint(s) of evaluation of this end point: until 10 hours after the allergen challenge on Day 9

Secondary Outcome(s)

Secondary end point(s): • Early Asthmatic Response (EAR) on Day 9, defined as the weighted AUC of the FEV1 percent changes from post-diluent value from 5 minutes to 2 hours (FEV1 AUC0-2h);
• Maximum fall in FEV1 during EAR and LAR on Day 9 defined as the maximum decrease in the percent change in FEV1 between 5 minutes and 2 hours post-diluent for EAR and between 4 and 10 hours for LAR;
• Allergen induced changes in sputum eosinophils and neutrophils (absolute and %) and mediators (ECP, NE, IL-5, IL-8, Eotaxin) at 10 hours post-allergen challenge;
• Responsiveness to a methacholine (MCh) challenge 24 hours post-AC defined as the provocative MCh challenge concentration causing a 20% decrease in FEV1 (PC20 FEV1).

- Safety variables (vital signs, ECG, Adverse Events, clinical laboratory values, body mass index)
- pharmacokinetic parameters (systemic exposure of CHF 6001 and its main inactive metabolite)

Timepoint(s) of evaluation of this end point: - EAR on Day 9
- Maximum fall in FEV1 during EAR and LAR on Day 9
- Allergen induced changes at 10 hours post-allergen challenge
- Responsiveness to a MCh challenge 24 hours post-AC

Secondary ID(s)

CCD-1202-PR-0080

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.