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

NCT00538434 | Completed Phase 2 Results DMC

• 1 other identifier: Res-05-0002
• Study Type: interventional
• Target: 227
• Locations: 2 countries
• Sites: 37

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.

Conditions

Eosinophilic Esophagitis

Keywords

Eosinophilic Esophagitis; GERD; EE; Reslizumab; IL-5; Interleukin-5; Cinquil

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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)

• 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)

Study Arms (4)

Reslizumab 1 mg/kg

EXPERIMENTAL

reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles

Biological: Reslizumab

Reslizumab 2 mg/kg

EXPERIMENTAL

reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles

Biological: Reslizumab

Reslizumab 3 mg/kg

EXPERIMENTAL

reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles

Biological: Reslizumab

Placebo

PLACEBO COMPARATOR

saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles

Other: Saline

Interventions

Reslizumab BIOLOGICAL

Also known as: CTx55700, Cinquil™, CEP-38072

Reslizumab 1 mg/kg; Reslizumab 2 mg/kg; Reslizumab 3 mg/kg

Saline OTHER

Placebo

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ception Therapeutics: lead

Study Sites (37)

The Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Arizona Dept. of Pediatrics

Tucson, Arizona, 85724, United States

Location

Arkansas Children's Hospital/University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72202, United States

Location

Kaiser Permanente Hospital- Pediatric Gastroenterology

Hayward, California, 94545, United States

Location

Children'S Hospital of Orange County Pediatric Subspecialty Faculty Division of Allergy and Asthma

Orange, California, 92868, United States

Location

Pediatric Allergy/Immunology

Palo Alto, California, 94305, United States

Location

Children's Hospital of San Diego

San Diego, California, 92123, United States

Location

Denver Childrens At Aurora, Colorado

Aurora, Colorado, 80045, United States

Location

1st Allergy and Clinical Research Center

Centennial, Colorado, 80112, United States

Location

Thomas Jefferson University Medical College

Wilmington, Delaware, 19803, United States

Location

Children's Center for Digestive Health Care

Atlanta, Georgia, 30342, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Children'S Memorial Hospital Division of Gastroenterology Hepatology & Nutrition

Chicago, Illinois, 66014, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Tuft's Floating Hospital

Boston, Massachusetts, 02111, United States

Location

Minnesota Gastroenterology

Plymouth, Minnesota, 55446, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Creighton University Medical Center

Omaha, Nebraska, 68131, United States

Location

Las Vegas Pediatric Gastroenterology Associates

Las Vegas, Nevada, 89109, United States

Location

South Jersey Pediatric Gastroenterology

Mays Landing, New Jersey, 08330, United States

Location

Mount Sinai School of Medicine, Pediatrics

New York, New York, 10029, United States

Location

State University of New York (SUNY)

Syracuse, New York, 13210, United States

Location

Center for Digestive Allergic and Immunologic Diseases

Williamsville, New York, 14221, United States

Location

Pediatric Allergy and Immunology of Duke Medical Center

Durham, North Carolina, 27720, United States

Location

Cincinnati Children's

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Greenville Health System

Greenville, South Carolina, 29615, United States

Location

University of Texas Southwest Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84113, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Carilion Medical Center for Children

Roanoke, Virginia, 24013, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Pediatric Allergy and Immunology

Edmonton, Alberta, T6G 2C8, Canada

Location

Pediatric Allergy & Immunology

Edmonton, Alberta, T6G2C8, Canada

Location

University of Montreal

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• 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.

  PMID: 22206777 RESULT

MeSH Terms

Conditions

Eosinophilic Esophagitis; Gastroesophageal Reflux

Interventions

reslizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Esophageal Motility Disorders; Deglutition Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

215-591-3000

Study Officials

• Sponsor's Medical Expert, MD

  Cephalon (Ception)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2007
• First Posted: October 2, 2007
• Study Start: March 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: September 2, 2016
• Results First Posted: September 2, 2016

Record last verified: 2016-07

Locations

US (34); CA (3)