A Study to Evaluate the Efficacy of MEDI-528 on Late Asthmatic Response With Atopic Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00394654
First received: October 31, 2006
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

This is a Phase 2a, randomized multicenter study to evaluate the efficacy of MEDI-528 on LAR in adult patients with atopic asthma.


Condition Intervention Phase
Asthma
Biological: MEDI-528 9 mg/kg
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2A, Randomized, Double-Blind, Placebo-Controlled Multicenter Study to Evaluate the Efficacy of MEDI-528, a Humanized Anti-Interleukin-9 Monoclonal Antibody, on Late Asthmatic Response Induced By Allergen Inhalation In Adults With Atopic Asthma

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Effect of MEDI-528 on Late Asthmatic Response (LAR) After Inhaled Allergen Challenge at Day 7 [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
    Change from baseline (percent reduction) in mean maximum decline of forced expiratory volume in one second (FEV1) during LAR at 3 to 7 hours after an inhaled allergen challenge.

  • Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 28 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Change from baseline (percent reduction) in mean maximum decline of FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

  • Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 56 [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
    Change from baseline (percent reduction) in mean maximum decline of FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

  • Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 7 [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
    Change from baseline (percent reduction) in mean maximum decline of area under the concentration-time curve (AUC) of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

  • Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 28 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Change from baseline (percent reduction) in mean maximum decline of AUC of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.

  • Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 56 [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
    Change from baseline (percent reduction) in mean maximum decline of AUC of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge.


Secondary Outcome Measures:
  • Incidence of Adverse Events [ Time Frame: Days 0 - 126 ] [ Designated as safety issue: Yes ]
    Number of participants experiencing adverse events (includes both adverse events and serious adverse events)

  • Incidence of Serious Adverse Events [ Time Frame: Days 0 - 126 ] [ Designated as safety issue: Yes ]
    Number of participants experiencing serious adverse events

  • Incidence of Anti-drug Antibodies (ADA) to MEDI-528 [ Time Frame: Days 0, 27, 55, 84, and 126 ] [ Designated as safety issue: Yes ]
    Number of participants with ADA to MEDI-528

  • Time to Observed Maximum Serum Concentration (Tmax) [ Time Frame: Days 0, 6, 7, 27, 55, 84, and 126 ] [ Designated as safety issue: No ]
    Tmax of MEDI-528 in serum

  • Time to Observed Maximum Sputum Concentration (Tmax) [ Time Frame: Days -21 to -7, 7, 28, and 56 ] [ Designated as safety issue: No ]
    Tmax of MEDI-528 in sputum

  • Time to Observed Maximum Nasal Lavage Concentration (Tmax) [ Time Frame: Days -6 to -1, 8, 29, and 57 ] [ Designated as safety issue: No ]
    Tmax of MEDI-528 in nasal lavage

  • Observed Maximum Serum Concentration (Cmax) [ Time Frame: Days 0, 6, 7, 27, 55, 84, and 126 ] [ Designated as safety issue: No ]
    Cmax of MEDI-528 in serum

  • Observed Maximum Sputum Concentration (Cmax) [ Time Frame: Days -21 to -7, 7, 28, and 56 ] [ Designated as safety issue: No ]
    Cmax of MEDI-528 in sputum

  • Observed Maximum Nasal Lavage Concentration (Cmax) [ Time Frame: Days -6 to -1, 8, 29, and 57 ] [ Designated as safety issue: No ]
    Cmax of MEDI-528 in nasal lavage

  • Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)] [ Time Frame: Days 0, 6, 7, 27, 55, 84, and 126 ] [ Designated as safety issue: No ]
    AUC(0-t) of MEDI-528 in serum

  • Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)] [ Time Frame: Days -21 to -7, 7, 28, and 56 ] [ Designated as safety issue: No ]
    AUC(0-t) of MEDI-528 in sputum

  • Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)] [ Time Frame: Days -6 to -1, 8, 29, and 57 ] [ Designated as safety issue: No ]
    AUC(0-t) of MEDI-528 in nasal lavage

  • Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] [ Time Frame: Days 0, 6, 7, 27, 55, 84, and 126 ] [ Designated as safety issue: No ]
    AUC(0-infinity) of MEDI-528 in serum

  • Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] [ Time Frame: Days -21 to -7, 7, 28, and 56 ] [ Designated as safety issue: No ]
    AUC(0-infinity) of MEDI-528 in sputum

  • Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] [ Time Frame: Days -6 to -1, 8, 29, and 57 ] [ Designated as safety issue: No ]
    AUC(0-infinity) of MEDI-528 in nasal lavage

  • Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)] [ Time Frame: Days 0, 6, 7, 27, 55, 84, and 126 ] [ Designated as safety issue: No ]
    AUC(ext) of MEDI-528 in serum

  • Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)] [ Time Frame: Days -21 to -7, 7, 28, and 56 ] [ Designated as safety issue: No ]
    AUC(ext) of MEDI-528 in sputum

  • Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)] [ Time Frame: Days -6 to -1, 8, 29, and 57 ] [ Designated as safety issue: No ]
    AUC(ext) of MEDI-528 in nasal lavage

  • Terminal Phase Half-Life (T1/2) [ Time Frame: Days 0, 6, 7, 27, 55, 84, and 126 ] [ Designated as safety issue: No ]
    T1/2 of MEDI-528 in serum

  • Terminal Phase Half-Life (T1/2) [ Time Frame: Days -21 to -7, 7, 28, and 56 ] [ Designated as safety issue: No ]
    T1/2 of MEDI-528 in sputum

  • Terminal Phase Half-Life (T1/2) [ Time Frame: Days -6 to -1, 8, 29, and 57 ] [ Designated as safety issue: No ]
    T1/2 of MEDI-528 in nasal lavage

  • Total Body Clearance (CL) [ Time Frame: Days 0, 6, 7, 27, 55, 84, and 126 ] [ Designated as safety issue: No ]
    CL of MEDI-528 in serum

  • Terminal Phase Volume of Distribution (Vz) [ Time Frame: Days 0, 6, 7, 27, 55, 84, and 126 ] [ Designated as safety issue: No ]
    Vz of MEDI-528 in serum


Enrollment: 30
Study Start Date: November 2006
Study Completion Date: January 2008
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI528 9 mg/kg
MEDI-528 at a single dose of 9 mg/kg administered as an intravenous infusion
Biological: MEDI-528 9 mg/kg
MEDI-528 at a single dose of 9 mg/kg administered as an intravenous infusion
Placebo Comparator: PLACEBO
Placebo administered as a single intravenous infusion
Other: Placebo
Placebo administered as a single intravenous infusion

Detailed Description:

This study (MI-CP138) is a Phase 2a, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy of MEDI-528 on LAR in adult patients with atopic asthma. Approximately three investigative sites in Canada will participate in this study, with up to 40 evaluable patients randomized in a 1:1 ratio to receive MEDI-528 (9.0 mg/kg) or placebo as a single IV infusion.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female adults, age 18 through 65 years of age at the time of screening;
  • Written informed consent obtained from the patient prior to receipt of any study medication or beginning study procedures;
  • Previously documented diagnosis of asthma of > 1 year duration, based on episodic symptoms of airflow obstruction, at least partial reversibility of airflow obstruction, with alternative diagnoses (e.g., chronic obstructive pulmonary disease) ruled out;
  • AHR in the methacholine challenge test with a PC20 (provoking concentration of methacholine to cause a 20% fall in FEV1) ≤ 16 mg/mL (Crapo, 2000);
  • Have dual response of EAR, defined as a decrease in FEV1 ≥ 20% at 0 to 3 hours after inhalation, and LAR, defined as a decrease in FEV1 ≥ 15% 3 to 7 hours after inhalation, to inhaled allergen;
  • Asthma symptoms are adequately controlled on short-acting β2 agonists (e.g., albuterol) alone;
  • Have had no significant changes in regular asthma medications and no acute asthma exacerbations requiring corticosteroid rescue, hospitalization, or emergency department visits for at least 4 weeks prior to screening and up through the time of the first dose of study drug on Study Day 0.
  • Sexually active women, unless surgically sterile or at least 1 year post-menopausal, must have used an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 21 days prior to the first dose of study drug on Study Day 0, and must agree to continue using such precautions through Study Day 126. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active men, unless surgically sterile, must likewise use an effective method of birth control (condom) and must agree to continue using such precautions through Study Day 126;
  • Able to complete the follow-up period through Study Day 126, as required by the protocol.
  • Willing to forego other forms of experimental treatment and study procedures during the study; and
  • Able to provide spirometric readings that meet American Thoracic Society (ATS) standards (ATS, 1995).

Exclusion Criteria:

  • Receipt of MEDI-528 in any previous clinical study;
  • History of allergy or adverse reactions to any component of the MEDI-528 formulation;
  • Lung disease other than allergic asthma (e.g. chronic bronchitis);
  • Current use of any systemic or inhaled immunosuppressive drugs, including systemic and inhaled corticosteroids (topical corticosteroids are permitted), long-acting β2 agonists, leukotriene antagonists, cromolyn sodium, nedocromil sodium, theophylline or any inhaled or systemic medication for asthma other than short-acting β2 agonists, for at least 4 weeks prior to study drug administration on Study Day 0.
  • Current use of any β-adrenergic antagonist (e.g. propranolol).
  • Any disease or illness, other than asthma, that may require the use of systemic corticosteroids during the study period.
  • Acute illnesses or evidence of clinically significant active infection, such as fever ³ 38.0°C (100.5°F) at screening and through the time of the study drug administration on Study Day 0;
  • Current allergy-vaccination therapy (i.e., desensitization immunotherapy) with less than 3 months of stable maintenance doses prior to the baseline allergen inhalation challenge;
  • Receipt of any investigational drug therapy within 30 days or any biologic(s) within 5 half-lives of the agent prior to the first dose of study drug through Study Day 150;
  • Receipt of any therapy with a leukocyte-depleting agent unless recovery in white cell count has been documented before screening;
  • Pregnancy (sexually active females must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to study drug administration on Study Day 0);
  • Is a nursing mother at the time of study enrollment;
  • Evidence of infection with hepatitis B or C virus, or HIV-1 or HIV-2, or active infection with hepatitis A;
  • History of significant systemic disease (e.g., cancer; infection; coronary artery disease or other cardiovascular disease; or hematological, renal, hepatic, endocrinologic, neurologic, rheumatologic, or gastrointestinal disease);
  • History of cancer other than nonmelanoma skin cancer or cervical carcinoma-in-situ that have been treated successfully with curative therapy;
  • History of primary immunodeficiency;
  • History of pancreatitis;
  • History of use of tobacco products within 2 years of baseline or history of smoking >= 10 pack-years;
  • Elective surgery planned from the time of screening through Study Day 126;
  • Clinically significant abnormalities (other than asthma) upon physical examination prior to study drug administration on Study Day 0;
  • Clinically significant abnormality, as determined by the investigator, on 12-lead ECG or chest radiograph at the time of screening;
  • At the time of screening, any of the following abnormalities: aspartate transaminase (AST), alanine transaminase (ALT), or amylase > 1.5 × above the upper limits of normal (ULN); or serum creatinine > 1.3 × ULN; or any other abnormal laboratory values in the screening panel that, in the opinion of the principal investigator (PI), are judged to be clinically significant; or
  • Evidence of any systemic disease or respiratory disease (other than asthma), any finding upon physical examination or history of any disease that, in the opinion of the PI or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00394654

Locations
Canada, Ontario
McMaster University
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Saskatchewan
University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 0W8
Canada
Hopital Laval
Quebec, Canada, G1V 4G5
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Nestor Molfino, M.D. MedImmune LLC
  More Information

No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00394654     History of Changes
Other Study ID Numbers: MI-CP138
Study First Received: October 31, 2006
Results First Received: October 18, 2013
Last Updated: October 18, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on August 20, 2014