Effect of Dupilumab on the Muscle Function of the Esophagus (food Pipe) in Participants with Eosinophilic Esophagitis (EoE)

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Provision of signed and dated informed consent form

• Stated willingness to comply with all study procedures and availability for theduration of the study including regular follow-up with the study monitor.

• Persons aged 22-75 years of age, males and females, of all ethnic races.

• Participants must be diagnosed with PPI resistant eosinophilic esophagitis (EoE) (proven by endoscopic biopsy showing > 15 eosinophils/HPF prior to and 8 weeks aftertreatment with PPI) will be eligible to participate in the study.

• Ability to take subcutaneous medication and willing to adhere to the 12-weekDupilumab regimen.

• Eligible participants must not have taken inhalational, oral or IV steroids for atleast 8 weeks prior to the study.

Exclusion Criteria:

Participants will be excluded from the study if they have any of the followings:

• Prior participation in a Dupilumab clinical trial, or past or current treatment withDupilumab

• Initiation or change of a food-elimination diet regimen or re-introduction of apreviously eliminated food group in the 6 weeks prior to screening. Participants ona food-elimination diet must remain on the same diet throughout the study.

• Other causes of esophageal eosinophilia for the following conditions: hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), Participants with eosinophilic gastroenteritis areeligible, provided they meet other eligibility criteria.

• Active Helicobacter pylori infection, history of achalasia, Crohn's disease,ulcerative colitis, celiac disease, and prior esophageal surgery

• Participant with significant other medical condition that would prevent treatmentwith Dupilumab and close follow up of their EOE condition.

• Initiation, discontinuation, or change in the dosage regimen of the followingmedications within 8 weeks prior to the baseline endoscopy:

• Proton pump inhibitors (except for participants who require a PPI trial prior tobaseline endoscopy)

• Leukotriene inhibitors

• Nasal and/or inhaled corticosteroids

• Participants on a stable dose of these medications for at least 8 weeks prior to thebaseline endoscopy may be included in the study but must not change the dose duringthe study.

• Participants who have asthma and use an asthma medicine c) have atopic dermatitis,chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, or prurigonodularis and also have asthma, then do not change or stop their corticosteroidmedicine or other asthma medicine without talking to the investigators. This maycause other symptoms that were controlled by the corticosteroid medicine or otherasthma medicine to come back.

• Initiation, discontinuation, or change in the dosage regimen of SC immunotherapy (SCIT), participants on a stable dose of these medications for at least 1 year priorto visit 1 may be included in the study but must not change the dose during thestudy.

• Treatment with sublingual immunotherapy (SLIT)

• Treatment with oral immunotherapy (OIT) within 6 months prior to visit 1.

• The following treatments within 3 months prior to screening, or any condition that,in the opinion of the investigator, is likely to require such treatment(s) duringthe study:

• Systemic immunosuppressant/immunomodulating drugs, including but not limited tosystemic corticosteroids, omalizumab, cyclosporine, mycophenolate-mofetil,interferon-gamma [IFN-γ], Janus kinase inhibitors, azathioprine, and methotrexate:One-time use of a corticosteroid as a part of the anesthetic preparation used duringeach endoscopy procedure is allowed.

• Treatment with an investigational drug within 2 months or within 5 half-lives (ifknown), whichever is longer, prior to visit.

• Planned or anticipated use of any prohibited medications and procedures during thestudy

• Planned or anticipated major surgical procedure during the study.

• Treatment with a live (attenuated) vaccine within 4 weeks prior to the baselinevisit

• Active parasitic infection or suspected parasitic infection, unless clinical and (ifnecessary) laboratory assessments have ruled out active infection beforerandomization.

• Chronic or acute infection requiring treatment with systemic antibiotics,antivirals, or antifungals within 2 weeks before baseline visit. Note: A participantmay be re-screened after the infection resolves.

• Known or suspected immunodeficiency disorder, including history of invasiveopportunistic infections (e.g., tuberculosis [TB], non-tuberculous mycobacterialinfections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis,aspergillosis) despite infection resolution, or otherwise recurrent infections ofabnormal frequency, or prolonged infections suggesting an immune-compromised status,as judged by the investigator.

• Tuberculosis testing will be performed if required by regulatory authorities orethics committees (ECs).

• Known history of human immunodeficiency virus (HIV) infection

• Established diagnosis of hepatitis B viral infection at the time of screening orpositive for hepatitis B surface antigen (HBsAg) at the time of screening.Participants who have gained immunity for hepatitis B virus infection aftervaccination (participants who are HBsAg negative, hepatitis B surface antibody [HBsAb] positive, and hepatitis B core antibody [HBcAb] negative are eligible forthe study). Participants with positive HBcAb are eligible for the study only ifhepatitis B virus DNA level is undetectable.

• Established diagnosis of hepatitis C viral (HCV) infection at the time of screening.Participants positive for hepatitis C Ab are eligible for the study only if HCV RNAis negative.

• On current treatment for hepatic disease including but not limited to acute orchronic hepatitis, cirrhosis, or hepatic failure, or has evidence of liver diseaseas indicated by persistent (confirmed by repeated tests ≥2 weeks apart) elevatedtransaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) more than 3 times the upper limit of normal [ULN] during the screeningperiod)

• Any of the following abnormal lab values at screening:

• Platelets <100 ×103/μL

• Neutrophils <1.5 × 103/μL

• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 If an abnormalvalue is detected at screening, a repeat test should be performed to confirmthe abnormality. Only if the repeat test confirms the abnormality would theparticipant be categorized as a screen failure. eGFR will be calculated usingthe Modification of Diet in Renal Disease (MDRD) equation in adult participantsand using the Bedside Schwartz formula in participants <18 years of age.

• If the participant: are taking oral, topical, or inhaled corticosteroid medicines,have asthma and use an asthma medicine, have atopic dermatitis, chronicrhinosinusitis with nasal polyposis, eosinophilic esophagitis, or prurigo nodularisand also have asthma

• Do not change or stop corticosteroid medicine or other asthma medicine withouttalking to the investigators. This may cause other symptoms that were controlled bythe corticosteroid medicine or other asthma medicine to come back. "

• Severe concomitant illness (es) that, in the investigator's judgment, wouldadversely affect the participant's participation in the study. Examples include butare not limited to short life expectancy, uncontrolled diabetes, cardiovascularconditions (e.g., NYHA Class III or IV cardiac failure), severe renal conditions (e.g., severe nephrotic syndrome), hepatobiliary conditions (e.g., Child-Pugh classB or C), neurological conditions (e.g., demyelinating diseases), active majorautoimmune diseases (e.g., lupus, inflammatory bowel disease, rheumatoid arthritis,etc.), other severe endocrinologic, gastrointestinal, metabolic, pulmonary, orlymphatic diseases. The specific justification for participants excluded under thiscriterion will be noted in study documents (chart notes, case report forms [CRF].

• History of malignancy within 5 years prior to screening, except completely treatedin situ carcinoma of the cervix and completely treated non-metastatic squamous orbasal cell carcinoma of the skin.

• History of alcohol or drug abuse within 6 months prior to screening

• Any other medical or psychological condition including relevant laboratoryabnormalities at screening that, in the opinion of the investigator, suggest a newand/or insufficiently understood disease, may present an unreasonable risk to thestudy participant as a result of his/her participation in this clinical trial, maymake participant's participation unreliable, or may interfere with studyassessments. The specific justification for participants excluded under thiscriterion will be noted in study documents.

• Participant or his/her immediate family is a member of the investigational team

• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeedduring the study

• Heterosexual women of childbearing potential who are unwilling to practice highlyeffective contraception prior to the initial dose/start of the first treatment,during the study, and for at least 12 weeks after the last dose. Highly effectivecontraceptive measures include:

• Stable use of combined (estrogen and progestogen containing) hormonalcontraception (oral, intravaginal, transdermal) or progestogen-only hormonalcontraception (oral, injectable, implantable) associated with inhibition ofovulation initiated 2 or more menstrual cycles prior to screening

• Intrauterine device; intrauterine hormone-releasing system

• Bilateral tubal ligation

• Vasectomized partner

• And/or sexual abstinence.

• Postmenopausal women must have amenorrhea for at least 12 months in order not to beconsidered of childbearing potential. Pregnancy testing and contraception are notrequired for women with documented hysterectomy or tubal ligation.

• Sexual abstinence is considered a highly effective method only if defined asrefraining from heterosexual intercourse during the entire period of risk associatedwith the study treatments. The reliability of sexual abstinence needs to beevaluated in relation to the duration of the clinical trial and the preferred andusual lifestyle of the participant. ‡Periodic abstinence (calendar, symptom-thermal,post-ovulation methods), withdrawal (coitus interrupts), spermicides only, andlactation amenorrhea method are not acceptable methods of contraception. Femalecondom and male condom should not be used together.

• Known systemic hypersensitivity to Dupilumab or the excipients of the drug product.This includes hypersensitivity reactions such as anaphylaxis, serum sickness,angioedema, urticaria, rash, erythema nodosum, and erythema multiforme.

• If participant have or develop significant dysphagia, dilation of the esophagususing endoscopic, Savary or other kind of dilators will be allowed during thetreatment with Dupilumab.