Efficacy and Safety Study of Reslizumab to Treat Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years
Primary Purpose
Eosinophilic Esophagitis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Reslizumab
Saline
Sponsored by
About this trial
This is an interventional treatment trial for Eosinophilic Esophagitis focused on measuring Eosinophilic Esophagitis, GERD, EE, Reslizumab, IL-5, Interleukin-5, Cinquil
Eligibility Criteria
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)
Sites / Locations
- The Children's Hospital of Alabama
- University of Arizona Dept. of Pediatrics
- Arkansas Children's Hospital/University of Arkansas for Medical Sciences
- Kaiser Permanente Hospital- Pediatric Gastroenterology
- Children'S Hospital of Orange County Pediatric Subspecialty Faculty Division of Allergy and Asthma
- Pediatric Allergy/Immunology
- Children's Hospital of San Diego
- Denver Childrens At Aurora, Colorado
- 1st Allergy and Clinical Research Center
- Thomas Jefferson University Medical College
- Children's Center for Digestive Health Care
- University of Chicago
- Children'S Memorial Hospital Division of Gastroenterology Hepatology & Nutrition
- Riley Hospital for Children
- Sinai Hospital of Baltimore
- Tuft's Floating Hospital
- Minnesota Gastroenterology
- Saint Louis University
- Creighton University Medical Center
- Las Vegas Pediatric Gastroenterology Associates
- South Jersey Pediatric Gastroenterology
- Mount Sinai School of Medicine, Pediatrics
- State University of New York (SUNY)
- Center for Digestive Allergic and Immunologic Diseases
- Pediatric Allergy and Immunology of Duke Medical Center
- Cincinnati Children's
- Nationwide Children's Hospital
- Children's Hospital of Philadelphia
- Greenville Health System
- University of Texas Southwest Medical Center
- University of Utah School of Medicine
- Virginia Commonwealth University
- Carilion Medical Center for Children
- Medical College of Wisconsin
- Pediatric Allergy and Immunology
- Pediatric Allergy & Immunology
- University of Montreal
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Reslizumab 1 mg/kg
Reslizumab 2 mg/kg
Reslizumab 3 mg/kg
Placebo
Arm Description
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 IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00538434
Brief Title
Efficacy and Safety Study of Reslizumab to Treat Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years
Official Title
An Efficacy and Safety Study of Reslizumab (CTx55700) in the Treatment of Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years
Study Type
Interventional
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ception Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eosinophilic Esophagitis
Keywords
Eosinophilic Esophagitis, GERD, EE, Reslizumab, IL-5, Interleukin-5, Cinquil
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
227 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Reslizumab 1 mg/kg
Arm Type
Experimental
Arm Description
reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Arm Title
Reslizumab 2 mg/kg
Arm Type
Experimental
Arm Description
reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Arm Title
Reslizumab 3 mg/kg
Arm Type
Experimental
Arm Description
reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Intervention Type
Biological
Intervention Name(s)
Reslizumab
Other Intervention Name(s)
CTx55700, Cinquil™, CEP-38072
Intervention Type
Other
Intervention Name(s)
Saline
Primary Outcome Measure Information:
Title
Mean Percent Change From Baseline to End of Treatment in Peak Esophageal Eosinophil (EE) Levels
Description
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.
Time Frame
Baseline, End of Treatment (up to 15 weeks [+/- 4 days])
Title
Mean Change From Baseline in Physician's Esophageal Eosinophil (EE) Global Assessment At The End-of-Treatment Visit (or at Early Withdrawal)
Description
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.
Time Frame
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 Measure Information:
Title
Mean Change From Baseline to End of Treatment in EE Predominant Symptom Assessment
Description
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.
Time Frame
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)
Title
Mean Percent Change From Baseline to End of Treatment in the Child Health Questionnaire (CHQ)
Description
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.
Time Frame
Baseline, End of Treatment (up to 15 weeks +/- 4 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sponsor's Medical Expert, MD
Organizational Affiliation
Cephalon (Ception)
Official's Role
Study Director
Facility Information:
Facility Name
The Children's Hospital of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Arizona Dept. of Pediatrics
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Arkansas Children's Hospital/University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Kaiser Permanente Hospital- Pediatric Gastroenterology
City
Hayward
State/Province
California
ZIP/Postal Code
94545
Country
United States
Facility Name
Children'S Hospital of Orange County Pediatric Subspecialty Faculty Division of Allergy and Asthma
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Pediatric Allergy/Immunology
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Children's Hospital of San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Denver Childrens At Aurora, Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
1st Allergy and Clinical Research Center
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Thomas Jefferson University Medical College
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Children's Center for Digestive Health Care
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Children'S Memorial Hospital Division of Gastroenterology Hepatology & Nutrition
City
Chicago
State/Province
Illinois
ZIP/Postal Code
66014
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Tuft's Floating Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Minnesota Gastroenterology
City
Plymouth
State/Province
Minnesota
ZIP/Postal Code
55446
Country
United States
Facility Name
Saint Louis University
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Creighton University Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
Las Vegas Pediatric Gastroenterology Associates
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
South Jersey Pediatric Gastroenterology
City
Mays Landing
State/Province
New Jersey
ZIP/Postal Code
08330
Country
United States
Facility Name
Mount Sinai School of Medicine, Pediatrics
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
State University of New York (SUNY)
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Center for Digestive Allergic and Immunologic Diseases
City
Williamsville
State/Province
New York
ZIP/Postal Code
14221
Country
United States
Facility Name
Pediatric Allergy and Immunology of Duke Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27720
Country
United States
Facility Name
Cincinnati Children's
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Greenville Health System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
University of Texas Southwest Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Utah School of Medicine
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23219
Country
United States
Facility Name
Carilion Medical Center for Children
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24013
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Pediatric Allergy and Immunology
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2C8
Country
Canada
Facility Name
Pediatric Allergy & Immunology
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G2C8
Country
Canada
Facility Name
University of Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
22206777
Citation
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.
Results Reference
result
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Efficacy and Safety Study of Reslizumab to Treat Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years
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