Efficacy and Safety Study of Reslizumab to Treat Poorly Controlled Asthma

An Efficacy and Safety Study of Reslizumab in the Treatment of Poorly Controlled Asthma in Subjects With Eosinophilic Airway Inflammation

The purpose of this study is to determine the effectiveness and safety of reslizumab in the treatment of subjects with poorly controlled asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: Saline; Biological: Reslizumab

Detailed Description

Objectives:

Primary: To demonstrate the ability of reslizumab to improve asthma control in subjects with active asthma and eosinophilic airway inflammation.

Secondary:

• To study the ability of reslizumab to reduce induced sputum eosinophil (EOS) counts in subjects with asthma.
• To study the ability of reslizumab to reduce the number of eosinophilic clinical asthma exacerbations (CAE) in subjects with asthma. A CAE is defined as a ≥ 20% decrease in forced expiratory volume in 1 second (FEV1; absolute value) from the baseline value or a requirement for emergency treatment of asthma, hospital admission for asthma or treatment with three or more days of oral corticosteroids (OCS) for asthma worsening.
• To assess the safety and tolerability of reslizumab in subjects with asthma.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V4G5
    • Hôpital Laval
  • Alberta
    • Calgary, Alberta, Canada, T2N4N1
      • Heritage Medical Research Clinic, University of Calgary
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare
    • Kingston, Ontario, Canada, K7L 2V6
      • Queen's University, Richardson's House
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4J1C5
      • Hopital du Sacre-Couer de Montreal
• United States
  • California
    • Orange, California, United States, 92868
      • Children'S Hospital of Orange County-Pediatric Subspecialty Faculty
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Allergy & Clinical Research Center
    • Colorado Springs, Colorado, United States, 80907
      • Asthma & Allergy Associates, P.C.
    • Denver, Colorado, United States, 80206
      • National Jewish Medical & Research Center
  • Illinois
    • Normal, Illinois, United States, 61761
      • Sneeze, Wheeze & Itch Associates, LLC
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Pulmonary Disease & Critical Care Associates, P.A.
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University of School of Medicine
  • Nebraska
    • Papillion, Nebraska, United States, 68046
      • The Asthma & Allergy Center
  • New York
    • Cortland, New York, United States, 13045
      • Health Sciences Research at Asthma & Allergy
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Univeristy Health Services
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • David Bernstein
    • Sylvania, Ohio, United States, 43560
      • Toledo Center for Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Allergy, Asthma and Clinical Research Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon
  • Pennsylvania
    • Blue Bell, Pennsylvania, United States, 19422
      • Allergy and Asthma Specialists
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt Asthma Sinus Allergy Program & Research Centers
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23229
      • Virginia Adult & Pediatric Allergy and Asthma
  • Washington
    • Seatle, Washington, United States, 98105
      • ASTHMA, Inc
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Allergy, Asthma and Sinus Center
    • Madison, Wisconsin, United States, 53972
      • University of Wisconsin-Madison, Allergy/Asthma Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• written informed consent
• male or female subjects aged ≥ 18 to 75 years at time of screening
• female if she is of non-childbearing potential, or of childbearing potential and willing to use specific barrier methods specified in protocol
• confirmation of asthma
• symptoms consistent with a diagnosis of asthma that is poorly controlled with an inhaled corticosteroid as determined by an Asthma Control Questionnaire (ACQ) score ≥ 1.5
• requirement for treatment with high dose daily fluticasone and at least one other agent for the treatment of asthma not specifically excluded in the protocol
• requirement for >/= 3% eosinophils in induced sputum at Screening

Exclusion Criteria:

• a clinically important event that would interfere with study schedule or procedure or compromise subject safety
• a diagnosis of hypereosinophilic syndrome
• an underlying lung disorder
• a current smoker
• use of systemic immunosuppressive agents within 6 months of study
• current use of systemic corticosteroids
• received attenuated live attenuated vaccines within three months prior to study entry
• expected to be poorly compliant with study drug, procedures, visits
• aggravating factors that are inadequately controlled
• participation in any investigational drug or device study within 30 days prior to study entry
• participation in biologics study within 3 months prior to study entry
• receipt of anti-human interleukin-5 (hIL-5) antibody within 6 months of study entry
• female subjects who are pregnant or nursing
• concurrent infection or disease that may preclude assessment of eosinophilic esophagitis
• concurrent immunodeficiency (human immunodeficiency [HIV], or acquired immunodeficiency syndrome [AIDS] or congenital immunodeficiency).
• current suspected drug and/or alcohol abuse

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reslizumab 3 mg/kg; Reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Biological: Reslizumab; Other Names: CEP-38072; Cinquil™; CTx55700
Placebo Comparator: Placebo; Saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Other: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to End of Therapy in Asthma Control Questionnaire (ACQ) Score	The ACQ is a 7 question instrument. Each question has 7 possible answers of 0, 1, 2, 3, 4, 5, and 6. Each increasing value is an indication of poorer asthma control. At protocol specified visits, the participant answered questions 1 to 6, circling the response that best described how that participant was during the past week, on the basis of a daily diary for the week before the visit. At the actual visit, study center personnel reviewed the questions and responses with the participant and determined the response and score for question 7. The overall ACQ score was presented as the mean of these 7 individual scores and was a number between 0 and 6, but not necessarily an integer.	Baseline through End of Therapy (up to 15 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of ACQ Responders at End of Therapy	Responders were defined as participants achieving at least a 0.5 reduction from baseline to End of Therapy in ACQ score. The ACQ is a 7 question instrument. Each question has 7 possible answers of 0, 1, 2, 3, 4, 5, and 6. Each increasing value is an indication of poorer asthma control. At protocol specified visits, the participant answered questions 1 to 6, circling the response that best described how that participant was during the past week, on the basis of a daily diary for the week before the visit. At the actual visit, study center personnel reviewed the questions and responses with the participant and determined the response and score for question 7. The overall ACQ score was presented as the mean of these 7 individual scores and was a number between 0 and 6, but not necessarily an integer.	Baseline, End of Therapy (up to 15 weeks)
Change From Baseline to End of Therapy in Forced Expiratory Volume in the First Second (FEV1)	The change in FEV1 from baseline to End of Therapy was determined. FEV1 was measured during pulmonary function tests using standard spirometry measurements.	Baseline, End of Therapy (up to 15 weeks)
Change From Baseline to End of Therapy in Percent Predicted FEV1	The change in percent predicted FEV1 from baseline to End of Therapy was calculated from the FEV1 measured during pulmonary function tests using standard spirometry measurements. Each participant's percent predicted FEV1 was calculated by adjusting the FEV1 for age, sex, height and race. The percent predicted FEV1 was then calculated by comparing the predicted FEV1 to the observed FEV1 using the Crapo formula (Crapo et al 1981a, Crapo and Morris 1981b, Crapo et al 1982).	Baseline, End of Therapy (up to 15 weeks)
Mean Change From Baseline to End of Therapy in Induced Sputum Eosinophil Levels		End of Screening or Baseline, End of Therapy (up to 15 weeks)
Percentage of Participants With Clinical Asthma Exacerbations (CAEs)	A CAE was defined as a 20% or more decrease in forced expiratory volume in 1 second (FEV1, absolute value) from the baseline value, a requirement for emergency treatment of asthma, hospital admission for asthma, or treatment with 3 or more days of oral corticosteroids for asthma worsening.	up to 15 weeks
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation	Participants may have been included in more than 1 category. AEs summarized were those that began or worsened after dispensation of the study drug and before 30 days after the last dose of study drug. If the severity of an AE was missing, the AE was reported as "severe." If drug relationship of an AE was missing, the AE was reported as "probably related." WFT=withdrawn from treatment.	From start of study drug through 15 weeks + 30 days

Collaborators and Investigators

• Sponsor: Ception Therapeutics
• Collaborators: Cephalon
• Investigators: Study Director: Sponsor's Medical Expert, MD, Cephalon (Ception)

Publications and helpful links

General Publications

• Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, Wilkins HJ, Henkel T, Nair P; Res-5-0010 Study Group. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011 Nov 15;184(10):1125-32. doi: 10.1164/rccm.201103-0396OC. Epub 2011 Aug 18.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: January 4, 2008
• First Submitted That Met QC Criteria: January 4, 2008
• First Posted (Estimate): January 7, 2008

Study Record Updates

• Last Update Posted (Estimate): August 17, 2016
• Last Update Submitted That Met QC Criteria: July 18, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Reslizumab; Cinquil™
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Reslizumab
• Other Study ID Numbers: Res-5-0010