A Phase 2A Study to Evaluate the Safety and Effect on Exercise Challenge Testing of MEDI-528 in Adults With Asthma
Primary Purpose
Asthma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MEDI528 50 mg
PLACEBO
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring Asthma, Bronchitis
Eligibility Criteria
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.
Sites / Locations
- Institute of Healthcare Assessment, Inc
- National Jewish Medical and Research Center
- Waterbury Pulmonary Associates
- Univ. of South Florida, Asthma, Allergy & Immunology Clinical Research Unit
- Sneeze,Wheeze & Itch Associates, LLC
- Northeast Medical Research Associates, Inc
- The Clinical Research Center, LLC
- Creighton University
- Bernstein Clinical Research Center
- Calgary COPD & Asthma Program
- UHN- Toronto Western Hospital
- Centre de Recherche Appliquee en Allergie de Quebec
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
MEDI528 50 mg
PLACEBO
Arm Description
MEDI-528 at a dose of 50 mg administered as a subcutaneous injection twice weekly for 4 weeks
Placebo administered as a subcutaneous injection twice weekly for 4 weeks
Outcomes
Primary Outcome Measures
Incidence of Adverse Events
Number of participants experiencing adverse events (includes both adverse events and serious adverse events)
Incidence of Serious Adverse Events
Number of participants experiencing serious adverse events
Secondary Outcome Measures
Incidence of Anti-drug Antibodies (ADA) to MEDI-528
Number of participants with ADA to MEDI-528
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.
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.
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.
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.
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.
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.
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)
AUC of FEV1 at Day 28
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)
AUC of FEV1 at Day 56
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)
AUC of FEV1 at Day 150
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
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
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
Mean Trough Concentration (Cmin)
Cmin of MEDI-528
Mean Trough Concentration at Last Measurable Time Point (Cmin_last)
Cmin_last of MEDI-528
Half-life (T1/2)
T1/2 of MEDI-528
Accumulation Index
Ratio of trough concentrations after first (Day 0) and last (Day 24) dose of MEDI-528
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00590720
Brief Title
A Phase 2A Study to Evaluate the Safety and Effect on Exercise Challenge Testing of MEDI-528 in Adults With Asthma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Terminated
Why Stopped
Study is replaced by MI-CP198 per CPM.
Study Start Date
March 2008 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Asthma, Bronchitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MEDI528 50 mg
Arm Type
Experimental
Arm Description
MEDI-528 at a dose of 50 mg administered as a subcutaneous injection twice weekly for 4 weeks
Arm Title
PLACEBO
Arm Type
Placebo Comparator
Arm Description
Placebo administered as a subcutaneous injection twice weekly for 4 weeks
Intervention Type
Biological
Intervention Name(s)
MEDI528 50 mg
Intervention Description
MEDI-528 at a dose of 50 mg administered as a subcutaneous injection twice weekly for 4 weeks
Intervention Type
Other
Intervention Name(s)
PLACEBO
Intervention Description
Placebo administered as a subcutaneous injection twice weekly for 4 weeks
Primary Outcome Measure Information:
Title
Incidence of Adverse Events
Description
Number of participants experiencing adverse events (includes both adverse events and serious adverse events)
Time Frame
Days 0 - 150
Title
Incidence of Serious Adverse Events
Description
Number of participants experiencing serious adverse events
Time Frame
Days 0 - 150
Secondary Outcome Measure Information:
Title
Incidence of Anti-drug Antibodies (ADA) to MEDI-528
Description
Number of participants with ADA to MEDI-528
Time Frame
Days 0, 28, 56, 119, and 150
Title
Absolute Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
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.
Time Frame
Day 28 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Absolute Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
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.
Time Frame
Day 56 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Absolute Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
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.
Time Frame
Day 150 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Percent Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
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.
Time Frame
Day 28 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Percent Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
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.
Time Frame
Day 56 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Percent Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
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.
Time Frame
Day 150 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)
Description
AUC of FEV1 at Day 28
Time Frame
Day 28 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)
Description
AUC of FEV1 at Day 56
Time Frame
Day 56 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1)
Description
AUC of FEV1 at Day 150
Time Frame
Day 150 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Time to Return in Minutes to 90 Percent of Baseline Forced Expiratory Volume in 1 Second (FEV1)
Description
Time to return in minutes to 90 percent of baseline FEV1 (prior to exercise) after 30 minues of exercise on Day 28
Time Frame
Day 28 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Time to Return in Minutes to 90 Percent of Baseline Forced Expiratory Volume in 1 Second (FEV1)
Description
Time to return in minutes to 90 percent of baseline FEV1 (prior to exercise) after exercise on Day 56
Time Frame
Day 56 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Time to Return in Minutes to 90 Percent of Baseline Forced Expiratory Volume in 1 Second (FEV1)
Description
Time to return in minutes to 90 percent of baseline FEV1 (prior to exercise) after exercise on Day 150
Time Frame
Day 150 (15 minutes prior to exercise and 5, 10, 15, 20, and 30 minutes after exercise)
Title
Mean Trough Concentration (Cmin)
Description
Cmin of MEDI-528
Time Frame
Days 0, 3, 7, 10, 14, 17, 21, 24, 28, 32, 37, 42, 56, 70, 84, 119, and 150
Title
Mean Trough Concentration at Last Measurable Time Point (Cmin_last)
Description
Cmin_last of MEDI-528
Time Frame
Days 0, 3, 7, 10, 14, 17, 21, 24, 28, 32, 37, 42, 56, 70, 84, 119, and 150
Title
Half-life (T1/2)
Description
T1/2 of MEDI-528
Time Frame
Days 0, 3, 7, 10, 14, 17, 21, 24, 28, 32, 37, 42, 56, 70, 84, 119, and 150
Title
Accumulation Index
Description
Ratio of trough concentrations after first (Day 0) and last (Day 24) dose of MEDI-528
Time Frame
Days 0 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Parker, M.D.
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Institute of Healthcare Assessment, Inc
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
National Jewish Medical and Research Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Waterbury Pulmonary Associates
City
Waterbury
State/Province
Connecticut
ZIP/Postal Code
06708
Country
United States
Facility Name
Univ. of South Florida, Asthma, Allergy & Immunology Clinical Research Unit
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Sneeze,Wheeze & Itch Associates, LLC
City
Normal
State/Province
Illinois
ZIP/Postal Code
61761
Country
United States
Facility Name
Northeast Medical Research Associates, Inc
City
No. Dartmouth
State/Province
Massachusetts
ZIP/Postal Code
02747
Country
United States
Facility Name
The Clinical Research Center, LLC
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Creighton University
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
Bernstein Clinical Research Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45231
Country
United States
Facility Name
Calgary COPD & Asthma Program
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N4N1
Country
Canada
Facility Name
UHN- Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T2S8
Country
Canada
Facility Name
Centre de Recherche Appliquee en Allergie de Quebec
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V4M6
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
21356110
Citation
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.
Results Reference
derived
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A Phase 2A Study to Evaluate the Safety and Effect on Exercise Challenge Testing of MEDI-528 in Adults With Asthma
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