A Phase 2A Study to Evaluate the Safety and Effect on Exercise Challenge Testing of MEDI-528 in Adults With Asthma

A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety and Effect on Exercise Challenge Testing of Multiple Fixed Subcutaneous Doses of MEDI-528, A Humanized Anti-Interleukin-9 Monoclonal Antibody, in Adults With Stable Asthma and Exercise-Induced Bronchoconstriction

The main objective of this study is to evaluate the safety and tolerability of multiple fixed doses of MEDI-528 in adult patients with stable asthma and exercise-induced bronchoconstriction (EIB).

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Biological: MEDI528 50 mg; Other: PLACEBO

Detailed Description

The primary objective of this study is to evaluate the safety and tolerability of multiple fixed escalating SC doses of MEDI-528 in adult patients with stable asthma and exercise-induced bronchoconstriction (EIB).

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N1
      • Calgary COPD & Asthma Program
  • Ontario
    • Toronto, Ontario, Canada, M5T2S8
      • UHN- Toronto Western Hospital
  • Quebec
    • Quebec City, Quebec, Canada, G1V4M6
      • Centre De Recherche Appliquée en Allergie De Québec
• United States
  • California
    • San Diego, California, United States, 92120
      • Institute of HealthCare Assessment, Inc
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Waterbury Pulmonary Associates
  • Florida
    • Tampa, Florida, United States, 33613
      • Univ. of South Florida, Asthma, Allergy & Immunology Clinical Research Unit
  • Illinois
    • Normal, Illinois, United States, 61761
      • Sneeze,Wheeze & Itch Associates, LLC
  • Massachusetts
    • No. Dartmouth, Massachusetts, United States, 02747
      • Northeast Medical Research Associates, Inc
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • The Clinical Research Center, LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients must meet all of the following criteria:

• Male or female adults, age 18 through 50 years at the time of screening;
• Weight 50-100 kg and body mass index ≤ 35;
• Written informed consent obtained from the patient prior to receipt of any study medication or beginning study procedures;
• Documented clinical history of asthma and receiving stable treatment for ≥ 1 month prior to Study Day 0;
• Airway hyperresponsiveness (AHR) on methacholine inhalation challenge testing at screening (or a documented history within the past 6 months), with provoking concentration of methacholine to cause a 20% fall in FEV1(subscript) (PC20) ≤ 8 mg/mL (Crapo, 2000);
• Exercise-induced bronchoconstriction (EIB) with a decrease in FEV1 (subscript) of ≥ 15% from pre-exercise challenge testing level at screening;
• Able to provide spirometry readings that meet American Thoracic Society (ATS) and European Respiratory Society (ERS) standards (Miller, 2005);
• Women of childbearing potential, unless surgically sterile or at least 1 year post-menopausal, must use two effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom, spermicide, diaphragm, cervical cap, abstinence, contraceptive foam, or use of a condom by the sexual partner or sterile sexual partner) from screening through Study Day 0, and must agree to continue using such precautions through Study Day 150. Cessation of birth control after this point should be discussed with a responsible physician. Men, unless surgically sterile, must likewise use an effective method of birth control (condom with spermicide) and must agree to continue using such precautions from screening through Study Day 150;
• Able to complete the study period, including follow-up period, of up to approximately 150 days; and
• Willing to forego other forms of experimental treatment and study procedures during the study and for 30 days after the follow-up period is completed.

Exclusion Criteria:

Patients must have none of the following criteria:

• Receipt of MEDI-528 in any previous clinical study;
• History of allergy or reaction to any component of the study drug formulation;
• Lung disease other than asthma (eg, chronic obstructive pulmonary disease, cystic fibrosis);
• Forced expiratory volume in 1 second (FEV1-subscript) < 70% of predicted values at screening;
• Use of systemic immunosuppressive drugs including systemic corticosteroids, ICS with doses > 800 μg/day budesonide (or another ICS of equivalent dose), long-acting β2 agonists, cromolyn sodium, nedocromil sodium, leukotriene receptor antagonists, theophylline, or omalizumab from screening through Study Day 150;
• Current use of any β-adrenergic antagonist (eg, propranolol);
• Any disease or illness, other than asthma, that is likely to require the use of systemic corticosteroids during the study period;
• Acute illnesses or evidence of significant active infection, such as fever ≥ 38.0°C (100.5°F) from screening through Study Day 0;
• Current allergy vaccination therapy (desensitization immunotherapy);
• Receipt of any investigational drug therapy within 30 days or any biologic(s) within 5 half-lives of the agent prior to screening;
• Pregnancy (women of child bearing potential, unless surgically sterile or at least 1 year postmenopausal, must have a negative serum and urine pregnancy test at screening before methacholine inhalation challenge testing and a negative urine pregnancy test prior to study drug administration on Study Day 0);
• Breastfeeding or lactating woman;
• Evidence of infection with hepatitis B or C virus or HIV-1 or HIV-2, or active infection with hepatitis A; must have negative HIV-1, HIV-2, hepatitis A, B, and C tests at screening;
• History of cancer other than basal cell carcinoma of the skin or cervical carcinoma-in-situ treated with apparent success with curative therapy more than 1 year prior to Study Day 0;
• History of primary immunodeficiency
• History of pancreatitis or currently active gastroduodenal ulcer;
• Current use of tobacco products or a history of use of tobacco products of more than one cigarette per month or equivalent within 1 year prior to randomization or history of smoking of ≥ 10 pack-years;
• History of life-long urinary retention;
• History of anaphylaxis (defined as immediate life-threatening event requiring medical invention);
• Elective surgery planned from screening through Study Day 150;
• Clinically significant abnormality, as determined by the investigator, on 12-lead ECG or chest radiograph at screening;
• History of any disease, evidence of any current disease (other than asthma), any finding upon physical examination, or any laboratory abnormality, that, in the opinion of the investigator or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study; or
• Any employee of the research site who is involved with the conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI528 50 mg; MEDI-528 at a dose of 50 mg administered as a subcutaneous injection twice weekly for 4 weeks	Biological: MEDI528 50 mg; MEDI-528 at a dose of 50 mg administered as a subcutaneous injection twice weekly for 4 weeks
Placebo Comparator: PLACEBO; Placebo administered as a subcutaneous injection twice weekly for 4 weeks	Other: PLACEBO; Placebo administered as a subcutaneous injection twice weekly for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	Number of participants experiencing adverse events (includes both adverse events and serious adverse events)	Days 0 - 150
Incidence of Serious Adverse Events	Number of participants experiencing serious adverse events	Days 0 - 150

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Anti-drug Antibodies (ADA) to MEDI-528	Number of participants with ADA to MEDI-528	Days 0, 28, 56, 119, and 150
Absolute Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)	The clinical activity of MEDI-528 on exercise-induced bronchoconstriction was measured by exercise challenge testing expressed as the maximum change in FEV1 measured before and after exercising on Day 28.	Day 28 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Absolute Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)	The clinical activity of MEDI-528 on exercise-induced bronchoconstriction was measured by exercise challenge testing expressed as the maximum change in FEV1 before and after exercise on Day 56.	Day 56 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Absolute Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)	The clinical activity of MEDI-528 on exercise-induced bronchoconstriction was measured by exercise challenge testing expressed as the maximum change in FEV1 before and after exercise on Day 150.	Day 150 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Percent Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)	The clinical activity of MEDI-528 on exercise-induced bronchoconstriction was measured by exercise challenge testing expressed as the percent maximum change in FEV1 before and after exercise on Day 28.	Day 28 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Percent Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)	The clinical activity of MEDI-528 on exercise-induced bronchoconstriction was measured by exercise challenge testing expressed as the percent maximum change in FEV1 before and after exercise on Day 56.	Day 56 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Percent Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)	The clinical activity of MEDI-528 on exercise-induced bronchoconstriction was measured by exercise challenge testing expressed as the percent maximum change in FEV1 before and after exercise on Day 150.	Day 150 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)	AUC of FEV1 at Day 28	Day 28 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)	AUC of FEV1 at Day 56	Day 56 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)	AUC of FEV1 at Day 150	Day 150 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Time to Return in Minutes to 90 Percent of Baseline Forced Expiratory Volume in 1 Second (FEV1)	Time to return in minutes to 90 percent of baseline FEV1 (prior to exercise) after 30 minues of exercise on Day 28	Day 28 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Time to Return in Minutes to 90 Percent of Baseline Forced Expiratory Volume in 1 Second (FEV1)	Time to return in minutes to 90 percent of baseline FEV1 (prior to exercise) after exercise on Day 56	Day 56 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Time to Return in Minutes to 90 Percent of Baseline Forced Expiratory Volume in 1 Second (FEV1)	Time to return in minutes to 90 percent of baseline FEV1 (prior to exercise) after exercise on Day 150	Day 150 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Mean Trough Concentration (Cmin)	Cmin of MEDI-528	Days 0, 3, 7, 10, 14, 17, 21, 24, 28, 32, 37, 42, 56, 70, 84, 119, and 150
Mean Trough Concentration at Last Measurable Time Point (Cmin_last)	Cmin_last of MEDI-528	Days 0, 3, 7, 10, 14, 17, 21, 24, 28, 32, 37, 42, 56, 70, 84, 119, and 150
Half-life (T1/2)	T1/2 of MEDI-528	Days 0, 3, 7, 10, 14, 17, 21, 24, 28, 32, 37, 42, 56, 70, 84, 119, and 150
Accumulation Index	Ratio of trough concentrations after first (Day 0) and last (Day 24) dose of MEDI-528	Days 0 and 24

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Joseph Parker, M.D., MedImmune LLC

Publications and helpful links

General Publications

• Parker JM, Oh CK, LaForce C, Miller SD, Pearlman DS, Le C, Robbie GJ, White WI, White B, Molfino NA; MEDI-528 Clinical Trials Group. Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma. BMC Pulm Med. 2011 Feb 28;11:14. doi: 10.1186/1471-2466-11-14.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: December 27, 2007
• First Posted (Estimate): January 11, 2008

Study Record Updates

• Last Update Posted (Estimate): March 21, 2014
• Last Update Submitted That Met QC Criteria: February 4, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Asthma; Bronchitis
• 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: MI-CP143