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

Phase 2

Completed

Conditions: Eosinophilic Esophagitis

Interventions: Biological: Reslizumab
Other: Saline

Registration Number: NCT00538434

Lead Sponsor: Ception Therapeutics

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 227

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Reslizumab 1 mg/kg	Reslizumab	reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Reslizumab 2 mg/kg	Reslizumab	reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Placebo	Saline	saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Reslizumab 3 mg/kg	Reslizumab	reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles

Primary Outcome Measures

Name	Time	Method
Mean Percent Change From Baseline to End of Treatment in Peak Esophageal Eosinophil (EE) Levels	Baseline, End of Treatment (up to 15 weeks [+/- 4 days])	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.
Mean Change From Baseline in Physician's Esophageal Eosinophil (EE) Global Assessment At The End-of-Treatment Visit (or at Early Withdrawal)	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)	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.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline to End of Treatment in EE Predominant Symptom Assessment	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)	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.
Mean Percent Change From Baseline to End of Treatment in the Child Health Questionnaire (CHQ)	Baseline, End of Treatment (up to 15 weeks +/- 4 days)	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.

Trial Locations

Locations (37): Sinai Hospital of Baltimore
🇺🇸
Baltimore, Maryland, United States
Children's Center for Digestive Health Care
🇺🇸
Atlanta, Georgia, United States
Children'S Memorial Hospital Division of Gastroenterology Hepatology & Nutrition
🇺🇸
Chicago, Illinois, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
University of Texas Southwest Medical Center
🇺🇸
Dallas, Texas, United States
Saint Louis University
🇺🇸
St. Louis, Missouri, United States
State University of New York (SUNY)
🇺🇸
Syracuse, New York, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
South Jersey Pediatric Gastroenterology
🇺🇸
Mays Landing, New Jersey, United States
1st Allergy and Clinical Research Center
🇺🇸
Centennial, Colorado, United States
The Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
Children's Hospital of San Diego
🇺🇸
San Diego, California, United States
Denver Childrens At Aurora, Colorado
🇺🇸
Aurora, Colorado, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Creighton University Medical Center
🇺🇸
Omaha, Nebraska, United States
Las Vegas Pediatric Gastroenterology Associates
🇺🇸
Las Vegas, Nevada, United States
Pediatric Allergy and Immunology of Duke Medical Center
🇺🇸
Durham, North Carolina, United States
Cincinnati Children's
🇺🇸
Cincinnati, Ohio, United States
University of Utah School of Medicine
🇺🇸
Salt Lake City, Utah, United States
University of Arizona Dept. of Pediatrics
🇺🇸
Tucson, Arizona, United States
Arkansas Children's Hospital/University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Kaiser Permanente Hospital- Pediatric Gastroenterology
🇺🇸
Hayward, California, United States
Children'S Hospital of Orange County Pediatric Subspecialty Faculty Division of Allergy and Asthma
🇺🇸
Orange, California, United States
Pediatric Allergy/Immunology
🇺🇸
Palo Alto, California, United States
Thomas Jefferson University Medical College
🇺🇸
Wilmington, Delaware, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Tuft's Floating Hospital
🇺🇸
Boston, Massachusetts, United States
Minnesota Gastroenterology
🇺🇸
Plymouth, Minnesota, United States
Mount Sinai School of Medicine, Pediatrics
🇺🇸
New York, New York, United States
Center for Digestive Allergic and Immunologic Diseases
🇺🇸
Williamsville, New York, United States
Greenville Health System
🇺🇸
Greenville, South Carolina, United States
Pediatric Allergy and Immunology
🇨🇦
Edmonton, Alberta, Canada
Pediatric Allergy & Immunology
🇨🇦
Edmonton, Alberta, Canada
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States
Carilion Medical Center for Children
🇺🇸
Roanoke, Virginia, United States
University of Montreal
🇨🇦
Montreal, Quebec, Canada
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States