Efficacy and Safety Study of Reslizumab to Treat Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years

An Efficacy and Safety Study of Reslizumab (CTx55700) in the Treatment of Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years

This trial will study three doses of reslizumab versus placebo in children with eosinophilic esophagitis (EE). The objectives of the trial will be to study the effectiveness of reslizumab in improving the clinical signs and symptoms and reducing esophageal eosinophils as well as assessing the safety profile compared to placebo.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
      • Pediatric Allergy and Immunology
    • Edmonton, Alberta, Canada, T6G2C8
      • Pediatric Allergy & Immunology
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • University of Montreal
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The Children's Hospital of Alabama
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Dept. of Pediatrics
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital/University of Arkansas for Medical Sciences
  • California
    • Hayward, California, United States, 94545
      • Kaiser Permanente Hospital- Pediatric Gastroenterology
    • Orange, California, United States, 92868
      • Children'S Hospital of Orange County Pediatric Subspecialty Faculty Division of Allergy and Asthma
    • Palo Alto, California, United States, 94305
      • Pediatric Allergy/Immunology
    • San Diego, California, United States, 92123
      • Children's Hospital of San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Denver Childrens At Aurora, Colorado
    • Centennial, Colorado, United States, 80112
      • 1st Allergy and Clinical Research Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Thomas Jefferson University Medical College
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Center for Digestive Health Care
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 66014
      • Children'S Memorial Hospital Division of Gastroenterology Hepatology & Nutrition
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tuft's Floating Hospital
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Saint Louis University
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Las Vegas Pediatric Gastroenterology Associates
  • New Jersey
    • Mays Landing, New Jersey, United States, 08330
      • South Jersey Pediatric Gastroenterology
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine, Pediatrics
    • Syracuse, New York, United States, 13210
      • State University of New York (SUNY)
    • Williamsville, New York, United States, 14221
      • Center for Digestive Allergic and Immunologic Diseases
  • North Carolina
    • Durham, North Carolina, United States, 27720
      • Pediatric Allergy and Immunology of Duke Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwest Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah School of Medicine
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
    • Roanoke, Virginia, United States, 24013
      • Carilion Medical Center for Children
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• written informed consent obtained
• male or female patients aged 5 to 18 years at time of screening
• of non-childbearing potential, of childbearing potential and willing to use specific barrier methods outlined in the protocol
• confirmed active EE (at Screening or within six weeks prior to Baseline Visit) as defined by esophageal mucosal eosinophils greater than or equal to 24 per high power field (hpf; 400X magnification)
• within the week prior to dosing, patient has one of the following symptoms of moderate (or worse) severity: vomiting, regurgitation (acid taste or feeling material movement upward), abdominal, chest pain/heartburn (burning or pain behind the sternum), or difficulty swallowing
• been on a therapeutic dose of proton pump inhibitors (PPIs; with or without histamine H2 receptor antagonists)for at least four weeks without resolution of symptoms, or by negative pH probe (with or without having failed a course of PPIs)

Exclusion Criteria:

• another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic syndrome [HES],Churg Strauss vasculitis, eosinophilic gastroenteritis [EG], or a parasitic infection)
• history of abnormal gastric or duodenal biopsy or documented gastrointestinal [GI] disorders (e.g., celiac disease, Crohn's disease or Helicobacter pylori infection)
• history of the following GI surgeries: fundoplication, gastric surgery or surgery for intestinal atresia
• use of systemic immunosuppressive or immunomodulating agents (anti-immunoglobulin E [IgE] monoclinal antibody [mAb], methotrexate, cyclosporin, interferon alpha [α], or anti tumor necrosis factor [TNF] mAb) within six months prior to study entry
• received attenuated live attenuated vaccines (e.g., measles, mumps, rubella [MMR], bacillus Calmette-Guerin [BCG], varicella, FluMist or polio) within three months prior to study entry
• use of swallowed inhaled corticosteroids for the treatment of EE within one month prior to study entry. Note: Inhaled and nasal corticosteroids for the treatment of asthma and allergies, respectively, are permitted provided that the dose remains the same during the study
• a stricture on endoscopy that prevents passage of the endoscope
• participation in any investigational drug or device study within 30 days prior to study entry
• female subjects who are pregnant or nursing
• concurrent infection or disease that may preclude assessment of EE
• concurrent immunodeficiency (human immunodeficiency [HIV], or acquired immunodeficiency syndrome [AIDS] or congenital immunodeficiency)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reslizumab 1 mg/kg; reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Biological: Reslizumab; Other Names: CEP-38072; Cinquil™; CTx55700
Experimental: Reslizumab 2 mg/kg; reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Biological: Reslizumab; Other Names: CEP-38072; Cinquil™; CTx55700
Experimental: Reslizumab 3 mg/kg; reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 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 up to 4 cycles	Other: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change From Baseline to End of Treatment in Peak Esophageal Eosinophil (EE) Levels	Participants underwent esophagogastroduodenoscopy (EGD) with biopsy (2 biopsies each at proximal and distal esophageal locations, plus any inflamed or abnormal areas) per standard clinical practice for the determination of esophageal eosinophils.	Baseline, End of Treatment (up to 15 weeks [+/- 4 days])
Mean Change From Baseline in Physician's Esophageal Eosinophil (EE) Global Assessment At The End-of-Treatment Visit (or at Early Withdrawal)	The investigator completed the Physician's EE Global Assessment based upon the participant's reporting of symptoms, weight, dietary status, and overall well-being. The assessment rated severity on a five-point scale (0=none to 4=very severe), taking into account physical findings, vital signs, the Subject's Predominant EE Symptom Assessment, the subject's diary data, and dietary questions. The Subject's Predominant EE Symptom was the EE symptom (vomiting/regurgitation, abdominal/chest pain, or dysphagia) that had the greatest negative impact on the subject based on patient diary data as of the baseline visit. The full range for change from baseline values is -4 (very severe at baseline, none at end of study) to 4 (none at baseline, severe at end of study). Negative change from baseline scores in the Physician's EE Global Assessment indicate improvement in EE status.	Baseline (Day 1, pre-treatment), End of Treatment (Week 15, 3 weeks [± 4 days] after the last dose of study drug, or at early withdrawal)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to End of Treatment in EE Predominant Symptom Assessment	Participants rated the severity of each EE symptom (vomiting/regurgitation, abdominal/chest pain, and dysphagia) based on the previous week's daily diary as none (=0), mild, moderate, severe, or very severe (=4). The predominant symptom was selected at the baseline visit and remained the same throughout the trial. The predominant symptom was defined as the EE symptom that had the greatest negative impact on the participant. The full range for change from baseline values is -4 (very severe at baseline, none at end of study) to 4 (none at baseline, severe at end of study). Negative change from baseline scores in the Patient's EE Predominant Symptom Assessment indicate improvement in the selected symptom.	Baseline (Day 1, pre-treatment), End of Treatment (Week 15, 3 weeks [± 4 days] after the last dose of study drug, or at early withdrawal)
Mean Percent Change From Baseline to End of Treatment in the Child Health Questionnaire (CHQ)	CHQ is a quality-of-life (QoL), observer-rated (the parent in this study) instrument designed to assess the general health and well-being of pediatric subjects aged 5 to 18 years. The instrument comprises 50 items that cover 14 unique physical and psychological concepts. Each item was scored separately following different scales and timeframes for response. Proprietary scoring algorithms are used. This outcome reports the two CHQ Summary Scores (Physical Summary Score and the Psychosocial Summary Scores) which are indexed to a 0 (poorest quality of life) to 100 (best quality of life) scores. The two summary scores are subsequently combined (via proprietary algorithm) to create the Global Health Summary Score (also on a 0-100 scale). Percent change from baseline values range from 100% (poorest QoL at baseline, best QoL at end of treatment) to -100% (best QoL at baseline, poorest QoL at end of treatment). Higher percent change from baseline values indicate improved QoL.	Baseline, End of Treatment (up to 15 weeks +/- 4 days)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G 3rd, O'Gorman MA, Abonia JP, Young J, Henkel T, Wilkins HJ, Liacouras CA. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012 Feb;129(2):456-63, 463.e1-3. doi: 10.1016/j.jaci.2011.11.044. Epub 2011 Dec 28.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 1, 2007
• First Submitted That Met QC Criteria: October 1, 2007
• First Posted (Estimate): October 2, 2007

Study Record Updates

• Last Update Posted (Estimate): September 2, 2016
• Last Update Submitted That Met QC Criteria: July 21, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: GERD; Eosinophilic Esophagitis; Reslizumab; Interleukin-5; EE; Cinquil; IL-5
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis; Anti-Asthmatic Agents; Respiratory System Agents; Reslizumab
• Other Study ID Numbers: Res-05-0002