Anti Inflammatory Lipid Mediators in Asthma Lipid Anti-Inflammtory Mediators in Asthma (ALMA; LIMA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Asthma
• Intervention / Treatment: Drug: CXA-10; Drug: Matching Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Asthma Research; Phone Number: 1 (844) 365-0852; Email: asthmaresearch@ucdenver.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Contact: Asthma Research; Phone Number: 844-365-0852

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. BMI >/= 30
3. 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
4. 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:

1. Respiratory tract infection within the last 4 weeks
2. Oral or systemic corticosteroid burst within the last 4 weeks
3. Asthma-related hospitalization within the last 6 weeks
4. Three or more asthma exacerbations requiring treatment with systemic corticosteroids in the past year consistent with severe asthma
5. Asthma-related ER visit within the previous 4 weeks
6. Current smoking or have former smokers that quit within the previous 1 year, or 10 pack years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CXA-10; 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; 6 weeks of treatment with 150 mg/day of orally administered CXA-10; Other Names: 10-nitro-9(E)-octadec-9-enoic acid
Placebo Comparator: Matching Placebo; 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; 6 weeks of treatment with orally administered matching placebo (to 150 mg/day of CXA-10)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Fernando Holguin, MD, MPH, University of Colorado Denver- Anschutz Medical Campus

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): January 30, 2030

Study Registration Dates

• First Submitted: August 1, 2018
• First Submitted That Met QC Criteria: November 30, 2018
• First Posted (Actual): December 3, 2018

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Inflammatory Agents; CXA-10
• Other Study ID Numbers: 19-0510; 21-3959; 5R01HL132550-03 (U.S. NIH Grant/Contract); 1R61HL157069-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No