Asthma
Conditions
Keywords
Asthma, Allergen induced asthma, ATS Criteria (1)
Brief summary
This is a Phase II, double-blind, placebo-controlled, cross-over trial to evaluate the efficacy of AIM-102 for the treatment of allergen-induced asthma. Individuals with stable, mild to moderate allergic asthma by American Thoracic Society (ATS) criteria (1), with a history of episodic wheeze and shortness of breath, will be eligible for enrollment. The patients will receive 4 consecutive days of dosing of AIM-102 or placebo (inactive product) with an allergen challenge on day 3 of dosing to see how the patient's lung function is changed by using AIM-102 or placebo.
Detailed description
This is a Phase II, double-blind, placebo-controlled, cross-over trial to evaluate the efficacy of AIM-102 for the treatment of allergen-induced asthma. Individuals with stable, mild to moderate allergic asthma by American Thoracic Society (ATS) criteria (1), with a history of episodic wheeze and shortness of breath, will be eligible for enrollment. The study is divided into 2 parts. Part 1: Screening Patients who meet all entry criteria will be screened with a history, physical examination, spirometry, and routine laboratory tests. If they continue to meet entry criteria, their atopic status will be documented by skin testing against common airborne allergens (including cat, dust mite, grass, pollen). Twenty-four (24) hr later, an allergen challenge will be performed to confirm the presence of an Early Asthmatic Response (EAR) and Late Asthmatic Response (LAR). Methacholine PC20 and sputum differentials will be performed before and after allergen challenges. Only patients with a documented early and late asthmatic response to inhaled incremental allergen challenge will be eligible for entry into Part 2 of the study. Part 2: Dosing and Follow-up Patients will be assigned to receive drug and placebo in a random order, with at least a two week washout between treatment periods. Spirometry, vital signs, and asthma symptomatology, methacholine challenge, sputum differentials will be evaluated before the first dose and again 24 hr before allergen challenge. Allergen challenge will be performed in the morning of Day 3 of dosing, post-dose, with spirometry measured until seven hr post-challenge. Sputum will also be induced at seven hr following the allergen challenge. Methacholine challenge and sputum induction will be performed 24 hr after allergen challenges. Any adverse events (AEs) and asthma symptoms will be evaluated at each clinic visit. A physical examination, vital signs, ECG, spirometry and laboratory tests will be repeated at the termination visit.
Interventions
DRUGAIM-102, D-cyclohexylalanine-D-glutamic-glycine tripeptide
AIM-102 is supplied as an oral solution. Dose is 15 mg of AIM-102 per kg of patient weight measured on Treatment Day 1 of each treatment phase The study drug will be administered for 4 consecutive days with at least a 2 week wash-out period prior to crossing over to the alternative treatment for 4 days.
DRUGBuffered Saline
The matching placebo is an oral solution of phosphate buffered saline
Sponsors
AIM Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
The following inclusion must be met for study entry (Part 1 - Screening): * Males and females between ≥ 18 and ≤ 65 years of age. * Able and willing to provide written informed consent to participate in the study, in accordance with ICH GCP requirements. * Non or ex-smoker, defined by an ex-smoker is defined as someone who completely stopped smoking for at least 12 months before Visit 1 of this study. * Able to adhere to study procedures. * In good general health without clinically significant medical history (see also
Exclusion criteria
below). * Physical examination and laboratory results within the normal ranges, if not within the ranges, they must be without clinically significance within 28 days prior to dosing. * Available for follow-up for the duration of the study (i.e. up to 10 weeks, including the Screening and Treatment Phases). * Mild to moderate, stable, allergic asthma by the ATS criteria (1) * History of episodic wheeze and shortness of breath; FEV1 at baseline at least 70% of the predicted value * Males agree to practice adequate contraception throughout the duration of the study and up to one month after drug administration. FEMALE-SPECIFIC INCLUSION CRITERIA: * All females must have a negative serum pregnancy test at Screening Days -5 to -1 (Visit 5) and a negative urine pregnancy test at Day 1 of each Treatment Phase prior to dosing (Visits 6 and 11). * A female patient must meet one of the following criteria: * No reproductive potential, defined as: menopausal for at least two years or surgically sterile for at least six months (i.e. has undergone hysterectomy, bilateral oophorectomy or tubal ligation) OR * Participant agrees to be heterosexually inactive from Screening Visit 1 until one month post final dose OR * Participant agrees to consistently practice adequate contraception from Screening Visit 1 until one month post final dose by one of the following methods, two methods must be used if hormonal contraception is used: Contraceptive pills (stable dose for at least 2 months prior to dosing on Day 1 (Visit 6) or patch, Norplant or Provera; intrauterine device (IUD), condom with spermicide or diaphragm (cervical cap) with spermicide. In addition the inclusion criteria above, the following inclusion criteria must be met for entry into the Dosing Phase (Part 2): * Positive methacholine challenge (PC20 ≤ 16 mg/ml) * Positive skin-prick test to common aeroallergens (including cat, dust mite, grass, pollen) * Positive allergen-induced early and late airway bronchoconstriction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of the allergen-induced late asthmatic response (LAR) between AIM-102 and placebo. | Pre dose(s) and post dose(s) and 7 and 24 hours post allergen challenge | Spirometry and the presence and severity of asthma symptoms will be assessed immediately before and immediately after each dose. Baseline and allergen-induced methacholine PC20, allergen-induced bronchoconstriction and allergen-induced airway inflammation will be assessed. AUC and maximum decrease in FEV1 for the late response will be compared between treatments using a one-way analysis of variance for the effects of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Asthmatic Response | Pre-dose(s) and post-dose(s) and 3 hours after allergen challenge | Spirometry & the presence and severity of asthma symptoms will be assessed immediately before and immediately after each dose. Baseline and allergen-induced methacholine PC20, allergen-induced bronchoconstriction and allergen-induced airway inflammation will be assessed. Allergen-induced increase in airway responsiveness is assessed by measuring the log methacholine PC20 difference from 24 hours before to 24 hours after allergen challenge. |
| • Comparison of the allergen-induced changes in sputum eosinophils at 7 hr and 24 hr post allergen, between the AIM-102 and placebo | Pre-dose and post-dose(s) and 7 and 24 hours post allergen challenge | Allergen-induced sputum eosinophils will be compared between treatments using a two-way analysis of variance for the effects of treatment and time. |
| Comparison of allergen-induced inflammatory mediators at 7 hr and 24 hr post allergen, between AIM-102 and placebo. | Pre-dose and post-dose(s) and 7 and 24 hours post allergen challenge | The allergen-induced airway inflammatory cells will be compared between treatments using a two-way analysis of variance. |
| Comparison of the allergen-induced airway hyperresponsiveness at 24 hours (hr) post allergen, between AIM-102 and placebo | Pre-dose and 24 hours post allergen challenge | The allergen-induced airway hyperresponsiveness will be compared between treatments using a one-way analysis of variance for the effects of treatment. |
| To determine the pharmacokinetic (PK) profile of AIM-102 in normal healthy mild to moderate asthmatic patients upon repeat dosing of AIM-102 | Pre-dose for dosing Days 1, 2, 3, 4, & an optional Day 5, additional samples on Day 3 post-dose & allergen challenge,pre-dose, 1.5, 3, 4.5, 6, & 7.5 hr post-dose | Drug plasma concentration data will be analyzed using a non-compartmental approach to obtain the following PK parameters: * peak plasma concentration * time to peak plasma concentration * elimination rate constant * terminal or elimination half-life * area under the concentration time curve from time 0 to last quantifiable concentration * area under the concentration time curve from time 0, extrapolated to infinity * oral clearance * oral volume of distribution |
Countries
Canada
Outcome results
None listed