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Benralizumab for Eosinophilic Gastritis (ANTI-IL5RA)

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ClinicalTrials.gov Identifier: NCT03473977
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : April 17, 2018
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE February 28, 2018
First Posted Date  ICMJE March 22, 2018
Last Update Posted Date April 17, 2018
Actual Study Start Date  ICMJE March 30, 2018
Estimated Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
Induction of disease remission [ Time Frame: 3 years ]
Will be defined by the percentage of patients that achieve histological remission in the stomach as defined by peak eosinophil counts less than 30/hpf. Comparison between drug vs placebo will be the primary measurement endpoint.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03473977 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
  • changes in endoscopic features before and after treatment with benralizumab [ Time Frame: 3 years ]
    Change in endoscopic score from pre- to post-treatment with benralizumab or placebo as measured by standardized endoscopy scoring systems.
  • changes in histologic features before and after treatment with benralizumab [ Time Frame: 3 years ]
    Change in histologic score from pre- to post-treatment with benralizumab or placebo as measured by standardized histology forms specific to the diseases of interest.
  • changes in blood eosinophil counts before and after treatment with benralizumab [ Time Frame: 3 years ]
    Change in blood eosinophil count before and after treatment with benralizumab or placebo as measured by CBC with differential.
  • evaluate esophageal, gastric, and duodenal tissue transcriptome changes following benralizumab treatment. [ Time Frame: 3 years ]
    Baseline predictors and changes in expression of genes as assessed by whole genome RNA sequencing
  • changes in peak eosinophil counts in biopsies before and after treatment with benralizumab [ Time Frame: 3 years ]
    Change in peak eosinophil count in biopsies (esophageal, gastric, and/or duodenal, as applicable) pre- vs. post-treatment with benralizumab or placebo
  • changes in clinical symptoms before and after treatment with benralizumab for EG [ Time Frame: 3 years ]
    Change in symptoms from pre- to post-treatment with benralizumab or placebo as measured by patient-reported outcome measures.
  • changes in quality of life before and after treatment with benralizumab for adult EoE [ Time Frame: 3 years ]
    Quality of life for pediatric EoE measured by the EoE-Quality of Life Scale A (range 0-96, with 96 being the most impaired)
  • Assessment of Adverse Events and Serious Adverse Events to determine safety and tolerability of Benralizumab in subjects with EG [ Time Frame: 3 years ]
    Incidence and rate of severity of Adverse Events and Serious Adverse Events
  • Physical exam to evaluate the safety and tolerability of Benralizumab in subjects with EG [ Time Frame: 3 years ]
    incidence of clinically significant findings
Original Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
  • changes in endoscopic score before and after treatment with benralizumab [ Time Frame: 3 years ]
    Change in endoscopic score from pre- to post-treatment with benralizumab or placebo as measured by EREFS for EoE and Lanza Score for EG.
  • changes in histologic features before and after treatment with benralizumab [ Time Frame: 3 years ]
    Change in histologic score from pre- to post-treatment with benralizumab or placebo as measured by HSS for EoE and EG and ED Biopsy Evaluation Forms for EG or EGE
  • changes in blood eosinophil counts before and after treatment with benralizumab [ Time Frame: 3 years ]
    Change in blood eosinophil count before and after treatment with benralizumab or placebo as measured by CBC with differential.
  • evaluate esophageal, gastric, and duodenal tissue transcriptome changes following benralizumab treatment. [ Time Frame: 3 years ]
    Baseline predictors and changes in expression of genes as assessed by whole genome RNA sequencing
  • changes in peak eosinophil counts in biopsies before and after treatment with benralizumab [ Time Frame: 3 years ]
    Change in peak eosinophil count in biopsies (esophageal, gastric, and/or duodenal, as applicable) pre- vs. post-treatment with benralizumab or placebo
  • changes in clinical symptoms before and after treatment with benralizumab for EG [ Time Frame: 3 years ]
    Change in symptoms from pre- to post-treatment with benralizumab or placebo as measured by PROs
    • SODA (for EG)
  • changes in clinical symptoms before and after treatment with benralizumab for pediatric EoE [ Time Frame: 3 years ]
    -PEESSv2 (for pediatric EoE)
  • changes in quality of life before and after treatment with benralizumab for pediatric EoE [ Time Frame: 3 years ]
    Quality of life for pediatric EoE measured by PedsQL 3.0
  • changes in daily function, symptoms, behaviors, and feelings, before and after treatment with benralizumab for pediatric and adult EG/EoE [ Time Frame: 3 years ]
    Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
  • changes in quality of life before and after treatment with benralizumab for adult EoE [ Time Frame: 3 years ]
    Quality of life for pediatric EoE measured by EoE-QOL-A
  • Assessment of AE/SAE to determine safety and tolerability of Benralizumab in subjects with EG [ Time Frame: 3 years ]
    Incidence and rate of severity of AEs/SAEs
  • Physical exam to evaluate the safety and tolerability of Benralizumab in subjects with EG [ Time Frame: 3 years ]
    incidence of clinically significant findings
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Benralizumab for Eosinophilic Gastritis
Official Title  ICMJE A Double-Blind, Placebo-controlled Clinical Trial to Evaluate Efficacy of Benralizumab in Subjects With Eosinophilic Gastritis
Brief Summary A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Benralizumab (Anti-IL5RA) in Subjects With Eosinophilic Gastritis.
Detailed Description

Primary Objective:

To assess the efficacy of repeat subcutaneous (SC) doses of benralizumab, compared with placebo, to reduce eosinophilic inflammation in the gastrointestinal tract of patients with EG Secondary Objectives: To assess changes in endoscopic score/histological features/blood and biopsy eosinophil counts/clinical symptoms/esophageal, gastric, and duodenal tissue transcriptome changes/ before and after treatment with benralizumab.

26 subjects are planned to be enrolled into the study at Cincinnati Children's Hospital Medical Center.

Qualifying Subjects will receive 3 monthly sub-coetaneous injections of benralizumab/Placebo, followed by an option six month Open Label Extension period.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Participants will receive 3 doses of drug or placebo. An optional OLE will also be available following the double blind period.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
The study is double blind. Randomization will be performed by external investigational pharmacy staff, which the dispenser of the drug/placebo at CCHMC.
Primary Purpose: Treatment
Condition  ICMJE Eosinophilic Gastritis or Gastroenteritis
Intervention  ICMJE
  • Biological: Benralizumab
    Monoclonal antibody originally developed for the treatment of asthma. It is directed against the alpha-chain of the interleukin-5 receptor (CD125). Either Benralizumab or Placebo will be injected in 3 monthly doses of 30 mg, to examine the decrease in blood and tissue eosinophil counts in subjects with Eosinophilic Gastritis. This will be followed by an optional OLE period.
    Other Name: Fasenra
  • Biological: Placebo
    Placebo will be injected in 3 monthly doses of 30 mg, as a comparator to injection with Benralizumab to examine the decrease in blood and tissue eosinophil counts in subjects with Eosinophilic Gastritis.
Study Arms  ICMJE
  • Experimental: Benralizumab
    This Arm is a subcutaneous dose of 30 mg of Benralizumab
    Intervention: Biological: Benralizumab
  • Placebo Comparator: Placebo
    This Arm is a subcutaneous dose of 30 mg of Placebo
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 15, 2018)
26
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 30, 2021
Estimated Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
  • Males and females between the ages of 12-60 years with confirmed diagnosis of EG involving stomach; involvement of eosinophilic inflammation in other gastrointestinal segments will be allowed but not required or sufficient.
  • Histologically active EG at time of screening, with a peak Gastric count of ≥ 30 eos/hpf in at least 5 hpfs.
  • Must be symptomatic (defined as having experienced symptoms within 4 weeks prior to enrollment)
  • Blood eosinophilia (defined as having an absolute eosinophil count > 500 cells per mcL of blood ) at least once during the 6 months prior to enrollment.
  • Must be on baseline anti-EG/EGE therapy as long as there is agreement to not change their dosage unless medically indicated.
  • Clinical symptoms (i.e., abdominal pain, bloating, vomiting, diarrhea) severe enough to impact daily life (e.g., school/work attendance, social activities) ≥ 2 days/week for 3 of the 4 weeks prior to enrollment despite treatment (such as diet, proton pump inhibitors or corticosteroids). See addendum number 1, page 55.
  • Female subjects: Women of childbearing potential (WOCBP) must use an effective form of birth control (confirmed by the Investigator). Effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective IUD intrauterine device/IUS levonogestrel Intrauterine system, Depo-Provera(tm) injections, oral contraceptive, and Evra Patch(tm) or Nuvaring(tm). WOCBP must agree to use effective method of birth control, as defined above, from enrollment, throughout the study duration and within 16 weeks after last dose of IP, and have negative serum pregnancy test result on Visit 0.
  • Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of visit -1 without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
  • Women ≥50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
  • All male subjects who are sexually active must agree to use an acceptable method of contraception (condom with or without spermicide, vasectomy) from Visit 0 until 16 weeks after their last dose.

Exclusion Criteria:

  • Concurrent H. pylori gastritis or parasitic infection
  • Other gastrointestinal disorders such as Crohn's disease, inflammatory bowel disease, or Celiac disease
  • Esophageal stricture that prevents the easy passage of a standard endoscope
  • Use of any investigational biologic drug within 6 months prior to screening
  • Hypereosinophilic syndrome, defined by multiple organ involvement (with the exception of atopic disease or EGID) and persistent blood absolute eosinophil count ≥1500/mcL.
  • A diagnosis of celiac disease, inflammatory bowel disease, eosinophilic granulomatosis with polyangiitis (EGPA), drug hypersensitivity or connective tissue rheumatological disorders,
  • History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent, and assent when applicable was obtained. Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent, and assent when applicable, was obtained.
  • A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy.
  • Pregnant or nursing
  • Receipt of any investigational non-biologic within 30 days or 5 half-lives prior to visit 0, whichever is longer.
  • A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
  • Any other medical illness that precludes study involvement
  • Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to be enrolled.
  • Patients who are currently receiving or have previously received benralizumab or any other type of anti-interleukin therapy (i.e. mepolizumab, reslizumab, lebrikizumab etc.) within the last 6 months or 5 half-lives whichever is longer.
  • History of anaphylaxis to any biologic therapy or vaccine.
  • Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tal Cohen, MS 5135171074 tal.cohen@cchmc.org
Contact: Lauren DiTommaso 5138035446 lauren.DiTommaso@cchmc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03473977
Other Study ID Numbers  ICMJE CIN_"Benralizumab"_001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Hospital Medical Center, Cincinnati
Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: marc E Rothenberg, MD, PhD Children's Hospital Medical Center, Cincinnati
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP