A Phase IIa Repeat Dose AXP1275 vs Placebo Cross-over Trial With Pulmonary Allergen Challenge in Adults With Asthma

A Phase IIa Randomized Double-blind Placebo-controlled Two-way Cross-over Trial of the Effects of Repeat Doses of 50 mg AXP1275 Daily on the Asthmatic Response to a Pulmonary Allergen Challenge in Adults With Mild-to-Moderate Atopic Asthma

This is the first study in human patients with asthma that the sponsor is conducting in order to evaluate if there are signals that the investigational medication, AXP1275, may be a safe and effective treatment for asthma. The results of this study may help the sponsor to design additional studies.

Study Overview

• Status: Completed
• Conditions: Atopic Asthma
• Intervention / Treatment: Drug: AXP1275; Drug: AXP1275 matching placebo

Detailed Description

This 2-way, randomized, double-blind crossover study in subjects with mild to moderate atopic asthma is designed to compare the responses to allergen and methacholine challenges within the same subject after approximately 2 weeks of treatment with AXP1275 50 mg or placebo. A total of 20 subjects with asthma with a dual (early and late) asthmatic response to an inhaled aeroallergen will be randomized to 1 of 2 treatment sequences (placebo then AXP1275 or AXP1275 then placebo) in a double-blind fashion to receive either oral AXP1275 or matching placebo, once-daily, for 14 days. The washout period between the 2 treatment periods will be 14 to 21 days.

A post-treatment follow-up visit will occur 14 ± 3 days after completion of the second treatment period.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • IUCPQ, Institut de cardiologie et de pneumologie de l'Hôpital Laval
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital, The Lung Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 to 64 years (inclusive).
2. Male or female.
3. If male, is surgically sterile (vasectomy) or agrees to comply with required contraceptive measures.
4. If female, not pregnant (or lactating), as evidenced by a negative serum pregnancy test, and is either surgically sterile (hysterectomy, bilateral ovariectomy, or bilateral tubal ligation), or if a female of childbearing potential, agrees to comply with required contraceptive measures.
5. History of episodic wheeze and shortness of breath with a prebronchodilator FEV1 ≥70% of predicted at screening.
6. Asthma symptoms treated (if necessary) only with intermittent short-acting ß-agonist therapy by inhalation.
7. Demonstration of a positive wheal reaction on skin prick testing to at least 1 common aeroallergen at screening.
8. Screening inhalational allergen challenge response demonstrating that the subject experiences both an early asthmatic response (EAR) and a late asthmatic response (LAR).
9. Methacholine PC20 ≤16 mg/mL at screening.
10. No history of smoking within 6 months of screening, and with a total pack year history of ≤10 pack years.
11. 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the investigator.
12. All values for hematology, clinical chemistry, and urinalysis within the normal range, or if abnormal, are deemed not clinically significant by the investigator with documented agreement from the medical monitor.
13. Is able to give written informed consent.

Exclusion Criteria:

1. Past or present disease which, as judged by the investigator, may affect the outcome of this study.
2. Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the screening period.
3. Symptomatic allergic rhinitis. Those subjects with a history of allergic rhinitis may participate if asymptomatic at screening (and continue to be so at baseline on Day 1 prior to dosing) and if, in the opinion of the investigator, it is unlikely that disease exacerbation will occur during the course of the study.
4. History of life-threatening asthma.
5. Abnormal chest X-ray.
6. Use of oral, injectable, or dermal steroids within 3 months and/or inhaled steroids within 1 month of screening.
7. Use of cromoglycate, nedocromil, leukotriene receptor antagonists (zafirlukast, pranlukast, montelukast), and inhibitors of 5-lipoxygenase (zileuton) within 4 weeks of screening.
8. Use of immunosuppressives, anticoagulants (warfarin or heparin), or any medications that may interact with pharmacodynamic (PD) effects of AXP1275 within 4 weeks of screening.
9. Use of theophylline-containing agents (any type) and long-acting β2-agonists (salmeterol, formoterol) within 4 weeks of screening.
10. Positive screen for drug(s) of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, or benzodiazepines) or cotinine.
11. Positive for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) 1/2.
12. Has participated in a clinical trial and has received an investigational product within 30 days prior to screening, or 5 elimination half lives of the investigational product, whichever is longer.
13. Has had significant blood loss (>500 mL) or donation of blood within 2 months prior to screening visit 1.
14. History of being unable to tolerate or complete methacholine or allergen challenge tests.
15. Subject is undergoing allergen desensitization therapy.
16. History of immunotherapy in the 3 years prior to screening or concurrently undergoing immunotherapy treatment.
17. Professional or ancillary personnel involved in the study.
18. Is not, in the opinion of the investigator, suitable for entry into the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AXP1275; AXP1275 50 mg (2 × 25-mg capsules) once daily for 14 days	Drug: AXP1275; AXP1275 50 mg (2 × 25-mg capsules)
Placebo Comparator: AXP1275 matching placebo; AXP1275 matching placebo (2 capsules) once daily for 14 days	Drug: AXP1275 matching placebo; AXP1275 matching placebo (2 capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late Asthmatic Response	Area under the forced expiratory volume in 1 second (FEV1) curve from 3 to 7 hours after allergen challenge (AUC3-7h) on day 13 of both 14-day treatment periods.	From 3 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Asthmatic Response	Maximum percentage fall in FEV1 and AUC of FEV1 between 0 to 2 hours (AUC0-2h) after allergen challenge on day 13 of both 14-day treatment periods.	Between 0 to 2 hours after allergen challenge on day 13 of both 14-day treatment periods
Late Asthmatic Response-Secondary	Maximum percentage fall in FEV1 between 3 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods.	Between 3 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods
Total Asthmatic Response	Minimum FEV1 and AUC of FEV1 between 0-7 hours (AUC0 7h) after allergen challenge on day 13 of both 14-day treatment periods.	Between 0 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods
FEV1 comparison	For FEV1 values at each time point on day 12, 13, and 14, the difference between the two treatments will be calculated.	At day 12, 13, and 14 of both 14-day treatment periods
Sputum eosinophil count	Induced sputum eosinophil count per mL of sputum on days 12, 13, and 14 of both 14-day treatment periods.	On days 12, 13, and 14 of both 14-day treatment periods
Sputum cell count (other)	Induced sputum cell count per mL of sputum for cells other than eosinophils (including basophils) on days 1, 12, 13, and 14 of both 14-day treatment periods.	On days 1, 12, 13, and 14 of both 14-day treatment periods
CCL13 and CCL17 concentrations	Comparison of the two treatments for changes in sputum concentrations of CCL13 and CCL17.	On days 12, 13, and 14 of both 14-day treatment periods
Provocative concentration of methacholine	Shift in the provocative concentration of methacholine resulting in a 20% reduction in FEV1 (PC20) between days 1 and 12 and between days 12 and 14 of both 14-day treatment periods.	Between days 1 and 12 and between days 12 and 14 of both 14-day treatment periods
Maximum exhaled nitric oxide (eNO) and AUC of eNO	Maximum eNO and AUC of eNO on days 13 and 14 (AUC0-24h) of both 14-day treatment periods.	On days 13 and 14 of both 14-day treatment periods
eNO comparison	For eNO values at each time point on day 13, and 14 of both 14-day treatment periods, the difference between the two treatments will be calculated.	On days 13 and 14 of both 14-day treatment periods

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	The incidence of treatment-emergent AEs will be summarized by system organ class, preferred term, and maximum severity or strongest relationship to study treatment for both treatments. Serious AEs and AEs leading to early withdrawal from the study will also be listed.	Throughout both 14-day treatment periods
Clinical laboratory, vital signs, physical examination, and ECG changes	Clinical safety laboratory tests data will be listed by subject and visit with values falling outside the normal range provided in a separate listing. Shifts from abnormally low/normal/abnormally high at baseline to the end of the study will be shown. Data on physical examinations, vital signs, and ECGs will be listed.	Baseline to the end of the study (14 +/- 3 days from the last of two treatments)
AXP1275 plasma concentrations	AXP1275 plasma concentrations will be evaluated to determine if steady-state has been reached (minimum concentration [Cmin] on day 6 or 7) and for study drug dosing compliance purposes. In addition, concentrations at other time points will be evaluated relative to individual pharmacodynamic responses associated with a given time point.	day 6 or 7 (predose), day 12 (3 hr post dose), day 13 (3 and 10 hr post dose), and day 14 (3 hr post dose) for the active treatment arm

Collaborators and Investigators

• Sponsor: Axikin Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Louis-Philippe Boulet, MD, IUCPQ, Institut de cardiologie et de pneumologie de l'Hôpital Laval; Principal Investigator: Mark Fitzgerald, MD, University of British Columbia, Vancouver General Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: June 27, 2013
• First Posted (Estimate): July 1, 2013

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: January 8, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: AXP1275-201