Anti Inflammatory Lipid Mediators in Asthma Lipid Anti-Inflammtory Mediators in Asthma

Study Overview
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Brief Summary
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The main purpose of this Phase 2 double blind, placebo controlled crossover clinical study is to demonstrate the efficacy and safety of CXA-10 in obese adult asthmatics. Obesity induces a chronic systemic inflammatory state characterized by impaired adipokine signaling, pro-inflammatory cytokine responses, inflammatory cell activation and enhanced generation of oxidative inflammatory mediators. This impacts the lung, increasing the severity of asthma and its exacerbations. This research will evaluate how a synthetic nitro-fatty acid (CXA-10, 10-nitro-octadec-9-enoic acid) suppresses the systemic and airway inflammation that contributes to the obese asthmatic phenotype. Current data support the pleiotropic signaling actions of CXA-10 to induce adaptive signaling actions that beneficially modulate adipokine and cytokine expression and inhibit systemic and pulmonary inflammation. The investigators hypothesize that CXA-10 induced signaling responses will alleviate obesity-related airway hyperreactivity in obese adult asthmatics.

Official Title
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Anti Inflammatory Lipid Mediators in Asthma: A Double Blind Placebo Control Cross Over, Proof of Concept Study of CXA-10 to Reduce Bronchial Hyperresponsiveness in Obese Asthmatics; Lipid Anti-Inflammatory Mediators in Asthma to Reduce Hyperresponsiveness in Obese Asthmatics

Conditions
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Asthma, Obesity

Intervention / Treatment
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* Drug: CXA-10
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adequate completion of informed consent process with written documentation. Male and female patients, 18 to 65 years old. Female subjects should be either post-menopausal or surgically sterile, or, if child-bearing potential (WOCP) should agree to use an acceptable method of contraception, for the duration of the study, with a negative pregnancy test prior to entering the study. BMI >/= 30 Diagnosis of asthma: based on previous physician diagnosis for > 6 months, and baseline pre-bronchodilator (BD) FEV1 between 50 and 95% predicted with either a 12% or greater bronchodilator response to 4 puffs of albuterol or PC20 methacholine (16 mg) if <12% change post BD Regular treatment with inhaled corticosteroids (ICS) (up to 1000 mcg/day fluticasone/equivalent), long acting beta agonists (LABA), and/or long-acting muscarinic antagonists (LAMA), which can be combination medication for at least 3 months; on a stable dose for the 4 weeks prior to Visit 0 Exclusion Criteria: Respiratory tract infection within the last 4 weeks Oral or systemic corticosteroid burst within the last 4 weeks Asthma-related hospitalization within the last 6 weeks Three or more asthma exacerbations requiring treatment with systemic corticosteroids in the past year consistent with severe asthma Asthma-related ER visit within the previous 4 weeks Current smoking or have former smokers that quit within the previous 1 year, or 10 pack years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CXA-10<br>Administered orally, continuously, and daily for at least 6 weeks. Dispensed at Visit 1. Washout period of at least 4 weeks and then enter crossover phase of an additional 6 weeks. Drug will be dispensed at Visit 4. | Drug: CXA-10<br>* 6 weeks of treatment with 150 mg/day of orally administered CXA-10<br>* Other names: 10-nitro-9(E)-octadec-9-enoic acid;|
| Placebo Comparator: Matching Placebo<br>Administered orally, daily, and continuously for at least 6 weeks. Dispensed at Visit 1. Washout period of at least 4 weeks and then enter crossover phase of an additional 6 weeks. Placebo will be dispensed at Visit 4. | Drug: Matching Placebo<br>* 6 weeks of treatment with orally administered matching placebo (to 150 mg/day of CXA-10)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Methacholine challenge dose per spirometry | To determine CXA-10 efficacy, reduction of bronchial hyperresponsiveness determined by performing spirometry to see if there's a change in methacholine dose | Through study completion, up to 18 weeks | 
| Changes in pre-bronchodilator FEV1 per spirometry | To determine the efficacy of CXA-10 by improving FEV1 | Through study completion, up to 18 weeks |