Anti-Inflammatory Lipid Mediators in Asthma (ALMA)

Sally E. Wenzel MD

Status and phase: Withdrawn; Phase 2

Conditions: Asthma

Treatments: Drug: Placebo; Drug: CXA-10

Study type: Interventional

Funder types: Other

Identifiers

NCT03680976

PRO16020149

Details and patient eligibility

About

The purpose of this study is to demonstrate the efficacy and safety of 10-nitro-9(E)-octadec-9-enoic acid (CXA-10) in obese adult asthmatics. The study's hypothesis is that 150 mg/day of CXA-10 for 12 weeks will alleviate obesity-related airway hyper-reactivity in obese adult asthmatics.

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Adequate completion of informed consent process with written documentation. Male and female patients, 18 to 65 yrs old female subjects should be either post-menopausal, surgically sterile, or women of child-bearing potential (WOCP) with a negative pregnancy test prior to entering the study and who agree to use an acceptable method of contraception, for the duration of the study.
2. Diagnosis of asthma: based on previous physician diagnosis for > 6 months, and either baseline pre-bronchodilator (BD) FEV1 between 50 and 90% predicted with a 12% or greater bronchodilator response to 4 puffs of albuterol or PC20 methacholine (16 mg) if no BD response (<12% change), within 2 years of Visit 0. If no historical reversibility or historical PC20, and the participant does not reverse 12% at V0, the participant can return for V0a to meet this eligibility criteria.
3. Daily treatment with inhaled corticosteroids and long acting beta agonists (ICS/LABA) combination medication for at least 3 months; on a stable dose for the 4 weeks prior to Visit 0
4. Asthma control questionnaire ACQ > 1.5 & ≤ 3
5. Smoking history <10 pack years and no smoking in the last year
6. Body Mass Index (BMI) ≥ 30 kg/m2
7. Hemoglobin A1c (HbA1c) <8%
8. Average systolic blood pressure <160 or diastolic < 100 mmHg (average of three measurements))
9. Resting HR ≥45 beats per minute (BPM) after 5 minute rest at screening
10. QTcF interval (Fredericia's correction factor) must be ≤430 msec at screening and pre-dose for males and ≤450 msec for females.
11. For randomization: No exacerbations or treatment failures during the run in. Patients, who exacerbate or experience treatment failure during the run-in, may re-enroll 4 weeks after the exacerbation has resolved (completed course of systemic corticosteroids).

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 2 months

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. Significant or uncontrolled concomitant medical illness including (but not limited to) heart disease, cancer, or diabetes at the discretion of the investigator

7. History of ICU admission/intubation due to asthma in the past year

8. Current statins use, patients may stop and re-enroll after 4 weeks of stopping statins

9. Positive pregnancy test at screening and at pre-dose

10. Women who are breastfeeding

11. Women of childbearing potential who are unwilling to use an acceptable method of birth control.

12. Intolerance or hypersensitivity to the CXA-10 or it's excipients

13. Treatment with any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the beginning of dosing (this includes investigational formulations of marketed products, inhaled and topical drugs

14. Unable or unlikely to complete study assessments or the study intervention (i.e. bronchoscopy) poses undue risk to patient in the opinion of the Investigator;

15. Any kind of oral nitrates such as nitroglycerin

16. Any clinical history of cardiovascular events, arrhythmias, fainting, palpitations within the previous 3 years

17. Personal or family history of congenital prolonged QT syndromes or sudden unexpected death due to a cardiac reason

18. History of any primary malignancy, including a history of melanoma or suspicious undiagnosed skin lesions, with the exception of basal cell or squamous cell carcinomas of the skin

19. Cervical carcinoma in situ or other malignancies curatively treated and with no evidence of disease for at least 5 years

20. History of alcohol or drug abuse in the 6 month period prior to enrollment

21. Treatment with vitamins, herbal and dietary supplements within 7 days or 5 - ½ lives whichever is longer prior to dosing until the final study visit, whichever is longer prior to dosing until the final study visit. (may rescreen after a washout)

22. Resting heart rate ≥100 BPM after 5 minutes rest at screening

23. Subjects with any other clinically relevant ECG parameter abnormality (e.g., PR interval, QRS deviation) or any clinically significant ECG abnormality will be excluded from the study. Any clinically significant abnormalities on 12-lead ECG at screening including, but not limited to any of the following:

    • PR interval >200 msec or <120 msec
    • Non-specific intra-ventricular conduction delay (IVCD) with QRS duration ≥110 msec and where the morphology does NOT meet criteria for left (LBBB) or right bundle branch block (RBBB)
    • Incomplete RBBB as defined by QRS duration ≥110 msec but <120 msec with RBBB pattern
    • Complete RBBB and LBBB
    • Evidence of second- or third- degree AV block
    • Pathological Q-waves (Q-wave wider than 0.04 sec or depth greater than 0.4-0.5 mV)
    • Evidence of ventricular pre-excitation
    • Evidence of left axis deviation (left axis deviation is -30 to -90 degrees) but not normal leftward axis, ST-T wave abnormalities, LBBB and/or RBBB

24. Any clinically significant murmurs evident on auscultation of the heart (including evidence of mitral valve prolapse)

25. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3.0X upper limit of normal (ULN), gamma-glutamyl transferase (GGT) >3X ULN, and total bilirubin >2X ULN. If all liver function tests (LFTs) are within normal limits (WNL) and total bilirubin is elevated, examination of direct and indirect bilirubin may be conducted. Subjects with indirect total bilirubin up to 3X ULN are presumed to have Gilbert's syndrome and may be enrolled if all other LFTs are WNL

26. Any other condition and/or situation that causes the Investigator to deem a subject unsuitable for the study (e.g., due to expected study medication non-compliance, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures)

27. Diagnosis of HIV

28. Patients with multiple sclerosis on dimethyl fumarate (tecfidera)

29. Patients with asthma on biological therapy (i.e. mepolizumab, omalizumab)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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0 participants in 2 patient groups, including a placebo group

10-nitro-octadeca-9-enoic acid (CXA-10)

Experimental group

Description:

CXA-10 150 mg tablet taken orally once a day for 12 weeks

Treatment:

Drug: CXA-10

Placebo

Placebo Comparator group

Description:

Placebo 150 mg tablet taken orally once a day for 12 weeks

Treatment:

Drug: Placebo