Eosinophilic Esophagitis
Conditions
Interventions
Test group 1:tezepelumab 210mg
Placebo:Placebo
Test group 2:tezepelumab 420mg
Sponsors
The First Affiliated Hospital of Sun Yat-Sen University
Eligibility
Sex/Gender
All
Age
12 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Provision of signed and dated written informed consent/assent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this CSP. 2.Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent. 3.Weight >= 40 kg at Visit 1. 4.Previously established diagnosis of EoE by EGD and esophageal biopsy. 5.Participants who have symptomatic EoE as defined by a history of on average at least 2 episodes of dysphagia (any severity of food going down slowly or being stuck in the throat) per week in the 4 weeks prior to Visit 1. 6.Must have been on stabilized diet for at least 8 weeks prior to Visit 1 and be willing to remain on stabilized diet during the course of the study (stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups). 7.May be on any background PPI and/or STC, during the course of the study, as long as background medications have been stable for at least 8 weeks prior to the screening/run-in period (Visit 1) and there is agreement not to change background medication or dosage unless medically indicated, during the screening/run-in and treatment period. 8.Participants must have previously documented standard of care treatment, which could include PPI and/or STC and/or diet. 9.Participants currently on leukotriene inhibitors and/or steroid treatments for asthma or allergies that are inhaled or administered intranasally, must report a stable dose for at least 4 weeks prior to the screening/run-in period (Visit 1). 10.If a medication for EoE (including PPI and/or STC) is discontinued prior to the screening/run-in, there should be a washout period of at least 8 weeks prior to Visit 1. Discontinuation of any marketed biologic (monoclonal or polyclonal antibody) should have a washout period of 4 months or 5 half-lives prior to Visit 1, whichever is longer. 11.At randomization, participant must have the diagnosis of active EoE confirmed during the screening period of this study by a centrally-read esophageal biopsy (confirmed diagnosis defined as an eosinophil count of = 15 EOS/HPF at 2 or more esophageal levels). Two to 4 biopsies should be obtained from both the proximal and distal esophagus. Two to 4 biopsies can be taken from the mid-esophagus for additional evaluation. 12.At randomization, participant must have been adherent to daily diary assessments: a) Must have completed 70% of daily diary entries between Visit 1 and Visit AND b) Must have completed at least 8 of 14 daily diary entries in the 14 days prior to randomization. 13.At randomization, participant must have symptomatic EoE as defined by >= 4 episodes of dysphagia (DSQ >= 2) over the 2 weeks prior to randomization, documented in an eDiary, of which >= 2 episodes require liquids, coughing, or gagging, vomiting or medical attention to obtain relief (DSQ >= 3). 14.At randomization, participant must have remained on stabilized diet between Visit 1 and Visit 2. 15.Male and female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.(a) Female participants: o Negative serum pregnancy test for female participants of childbearing potential at Visit 1. o Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from
Exclusion criteria
Exclusion criteria: 1.Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, celiac disease, EGE, EG, eosinophilic enteritis, colitis, diverticulitis, irritable bowel syndrome, or other clinically significant gastrointestinal conditions as per investigator discretion. 2.Eosinophilic granulomatosis with polyangiitis vasculitis; 3.Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening. 4.Use of a feeding tube, or having a pattern of not eating solid food daily. 5.Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count > 1500 eosinophils/µL. 6.Esophageal dilation performed within 8 weeks prior to screening. 7.History of cancer: ? Participants 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 participant is in remission and curative therapy was completed at least 12 months prior to the date informed consent, and assent when applicable, was obtained. ? Participants who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to the date informed consent, and assent when applicable, was obtained. 8.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. 9.Evidence of active COVID-19 infection. 10.Evidence of a clinically significant infection or receiving treatment with antibiotics or antiviral medications within 7 days prior to Visit 1 or during the screening/run-in period. 11.Tuberculosis requiring treatment within 12 months prior to Visit 1. 12.A history of known immunodeficiency disorder including a positive HIV test. 13.Any other medical illness, including, but not limited to, cardiovascular, hepatic, renal, neurological, musculoskeletal, rheumatological, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and precludes study involvement. 14.Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Participants with a history of hepatitis B vaccination without history of hepatitis B are allowed to be enrolled. 15.History of anaphylaxis to any biologic therapy or vaccine. 16.Evidence of active liver disease, including jaundice or AST, ALT, or ALP greater than twice the ULN (laboratory results during screening and/or prior to first dose). 17.History of chronic alcohol or drug abuse within 12 months prior to Visit 1. 18.History of documented immune complex disease (Type 3 hypersensitivity reactions) to mAb administration. 19.Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures requiring general anesthesia or in-patient status for > 1 day during the conduct of the study. 20.Receipt of immunoglobulin or blood products within 30 days prior to screening (Visit 1). 21.Treatment with oral and/or sublingual immunotherapy within 6 months prior to screening (Visit 1). 22.Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, and sy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Histologic response rate;Change from baseline in DSQ score; | — |
Secondary
| Measure | Time frame |
|---|---|
| change from baseline in EoE EREF at Week24;change from baseline in EoE-HSS grade score at week 24;Histologic response rate at week 52;Change from baseline in DSQ score at week52;Change from baseline in EoE EREFS at Week 52;Change from baseline in peak esophageal eosinophil count (EOS/HPF);Response of achieving clinico-histological remission;Changes from baseline in PEESS Module (adolescents only);Change from baseline in EoE-HSS grade score;Change from baseline in peak esophageal eosinophil count (EOS/HPF);Changes from baseline in PEESS Module (adolescents only);PK and ADA;safety; | — |
Countries
China
Contacts
Public ContactYinglian Xiao
The First Affiliated Hospital of Sun Yat-Sen University
Outcome results
None listed