A Study to Evaluate the Safety and Tolerability of the Administration of MEDI-528 When Administered in Multiple Doses to Adults With Mild Persistent Asthma

A Phase 2A, Randomized, Double-Blind, Placebo-Controlled,Dose-Escalation Study to Evaluate the Safety and Tolerability of Multiple-Dose Subcutaneous Administration of MEDI-528, A Humanized Anti-Interleukin-9 Monoclonal Antibody,When Administered to Adults With Mild Persistent Asthma

The primary objective of this study is to evaluate the safety and tolerability of escalating multiple SC doses of MEDI-528 in adult patients with mild persistent asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: MEDI528 0.3 mg/kg; Biological: MEDI528 1 mg/kg; Biological: MEDI528 3 mg/kg; Other: PLACEBO

Detailed Description

The secondary objectives of this study are to:

1. Assess the PK of MEDI-528; and
2. Assess the IM of MEDI-528 in this patient population.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Hôpital Laval
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University
  • Quebec
    • Montréal, Quebec, Canada, H4J 1C5
      • Hopital Du Sacre-Coeur de Montreal
• United States
  • Colorado
    • Denver, Colorado, United States, 80230
      • Colorado Allergy & Asthma Centers, PC
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Northeast Medical Research Associates, Inc.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc.
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
  • Ohio
    • Sylvania, Ohio, United States, 43560
      • Toledo Center for Clinical Research
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female adults, age 18 through 65 years of age at time of screening;
• Weight ≤ 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;
• Previously documented diagnosis of asthma based on episodic symptoms of airflow obstruction such as wheezing or chest tightness, with alternative diagnoses (e.g., chronic obstructive pulmonary disease) ruled out;
• Currently receiving treatment with short-acting β2 agonists, ICS at doses ≤ 264 μg/day fluticasone or equivalent, or both (National Heart, Lung, and Blood Institute [NHLBI], 2002);
• FEV1 or peak expiratory flow (PEF) ≥ 80% of predictable value;
• Have had a diagnosis of mild persistent asthma, defined as having asthma symptoms with a frequency of more than twice a week but less than once daily, or nighttime symptoms with a frequency of more than twice a month but less than once a week (NHLBI, 2002);
• Have AHR based on documented clinical history of either methacholine inhalation challenge with PC20 ≤ 16 mg/mL or partial reversibility of ≤ 12% in FEV1 within the past 18 months (including screening);
• Able to provide spirometry readings that meet American Thoracic Society/European Respiratory Society standards (Miller, 2005);
• Sexually active females, unless surgically sterile or at least 1 year post-menopausal, must use an effective method of avoiding pregnancy (including oral, implanted, or transdermal 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, 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. Sexually active males, unless surgically sterile, must likewise use an effective method of birth control (condom) and must agree to continue using such precautions through Study Day 150;
• Ability to complete the study period, including follow-up period, of up to 150 days; and
• Willing to forego other forms of experimental treatment and study procedures during the study.

Exclusion Criteria:

• Receipt of MEDI-528 in any previous clinical study or prior randomization into the trial;
• History of allergy or reaction to any component of the MEDI-528 formulation;
• Lung disease other than persistent asthma (e.g. chronic bronchitis);
• FEV1 < 80% of predicted values;
• History of severe asthma or asthma exacerbation requiring intubation;
• Use of systemic immunosuppressive drugs including systemic corticosteroids or ICS with doses > 264 μg/day fluticasone or equivalent within 4 weeks prior to Study Day 0;
• Use of long-acting β2 agonists, theophylline, cromolyn sodium, nedocromil sodium, leukotriene receptor antagonists, or any other inhaled or systemic medication for asthma (except short-acting β2 agonists or ICS at doses ≤ 264 μg/day fluticasone or equivalent) within the 2 weeks prior to 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 significant active infection, such as fever ≥ 38.0°C (100.5°F) at screening and up through time of the first dose of study drug;
• Current allergy vaccination therapy (desensitization immunotherapy), with less than 3 months of stable maintenance doses prior to screening;
• 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);
• Lactating or breastfeeding woman;
• Evidence of infection with hepatitis B or C virus, or human immunodeficiency virus-1 or -2 (HIV-1 or HIV-2), or active infection with hepatitis A;
• History of significant systemic disease (e.g., cancer, infection, hematological, renal, hepatic, coronary artery disease or other cardiovascular disease, endocrinologic, neurologic, rheumatologic, or gastrointestinal disease);
• History of cancer other than non-melanoma skin cancer or cervical carcinoma-in-situ treated with apparent success with curative therapy (remission for ≥ 1 year prior to screening);
• History of primary immunodeficiency;
• History of pancreatitis;
• 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;
• Elective surgery planned during the study period through Study Day 150;
• Clinically significant abnormalities on physical examination (other than asthma) prior to the first dose of study drug (including but not limited to splenomegaly); Clinically significant abnormality, as determined by the investigator, on 12-lead ECG, MRI, or chest radiograph at the time of screening;
• At the time of screening, any abnormality of the following measurements: hemoglobin, total white blood cell count (WBC), platelet count, aspartate transaminase (AST), alanine transaminase (ALT), amylase, or serum creatinine above the upper limits of normal (ULN); or other abnormal laboratory values in the screening panel that, in the opinion of the principal investigator, are judged to be clinically significant;
• 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 investigator or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study; or
• Employees of the clinical study site or any other individuals involved with the conduct of the study, or family members of such individuals.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI528 0.3 mg/kg; MEDI-528 at a dose of 0.3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks	Biological: MEDI528 0.3 mg/kg; MEDI-528 at a dose of 0.3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks
Experimental: MEDI528 1 mg/kg; MEDI-528 at a dose of 1 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks	Biological: MEDI528 1 mg/kg; MEDI-528 at a dose of 1 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks
Experimental: MEDI528 3 mg/kg; MEDI-528 at a dose of 3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks	Biological: MEDI528 3 mg/kg; MEDI-528 at a dose of 3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks
Placebo Comparator: PLACEBO; Placebo administered twice weekly as a subcutaneous (SC) dose for 4 weeks	Other: PLACEBO; Placebo administered twice weekly as a subcutaneous (SC) dose 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
Incidence of Abnormal Troponin Levels	Number of participants with troponin levels greater than upper limit of normal	Days 0, 14, 28, 56, 84, and 150
Incidence of Abnormal Clinically Significant Electrocardiogram (ECG) Results	Number of participants with abnormal clinically significant ECG results	Days -14 to -1, 14, 28, 56, 84, and 150
Incidence of Abnormal Clinically Significant Magnetic Resonance Imaging (MRI) Results	Number of participants experiencing abnormal clinically significant MRI results	Days -14 to -1 and 28

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, 84, 119, and 150
Time to Observed Maximum Serum Concentration (Tmax)	Tmax of MEDI-528	Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150
Observed Maximum Serum Concentration (Cmax)	Cmax of MEDI-528	Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150
Terminal Phase Half-life (T1/2)	T1/2 of MEDI-528	Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Joe 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: July 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: July 23, 2007
• First Submitted That Met QC Criteria: July 23, 2007
• First Posted (Estimate): July 25, 2007

Study Record Updates

• Last Update Posted (Estimate): December 11, 2013
• Last Update Submitted That Met QC Criteria: October 17, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• 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-CP131; NCT00507130 (Registry Identifier: ClinicalTrials.gov)