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

Open to people ages 22 years and up

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 the duration 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 after treatment with PPI) will be eligible to participate in the study.
• Ability to take subcutaneous medication and willing to adhere to the 12-week Dupilumab regimen.
• Eligible participants must not have taken inhalational, oral or IV steroids for at least 8 weeks prior to the study.

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 with Dupilumab
• Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 6 weeks prior to screening. Participants on a food-elimination diet must remain on the same diet throughout the study.
• Other causes of esophageal eosinophilia for the following conditions: hyper eosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), Participants with eosinophilic gastroenteritis are eligible, 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 treatment with Dupilumab and close follow up of their EOE condition.
• Initiation, discontinuation, or change in the dosage regimen of the following medications within 8 weeks prior to the baseline endoscopy:
• Proton pump inhibitors (except for participants who require a PPI trial prior to baseline endoscopy)
• Leukotriene inhibitors
• Nasal and/or inhaled corticosteroids
• Participants on a stable dose of these medications for at least 8 weeks prior to the baseline endoscopy may be included in the study but must not change the dose during the study.
• Participants who have asthma and use an asthma medicine c) have atopic dermatitis, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, or prurigo nodularis and also have asthma, then do not change or stop their corticosteroid medicine or other asthma medicine without talking to the investigators. This may cause other symptoms that were controlled by the corticosteroid medicine or other asthma 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 prior to visit 1 may be included in the study but must not change the dose during the study.
• 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) during the study:
• Systemic immunosuppressant/immunomodulating drugs, including but not limited to systemic 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 during each endoscopy procedure is allowed.
• Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to visit.
• Planned or anticipated use of any prohibited medications and procedures during the study
• Planned or anticipated major surgical procedure during the study.
• Treatment with a live (attenuated) vaccine within 4 weeks prior to the baseline visit
• Active parasitic infection or suspected parasitic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomization.
• Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before baseline visit. Note: A participant may be re-screened after the infection resolves.
• Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections (e.g., tuberculosis [TB], non-tuberculous mycobacterial infections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections suggesting an immune-compromised status, as judged by the investigator.
• Tuberculosis testing will be performed if required by regulatory authorities or ethics committees (ECs).
• Known history of human immunodeficiency virus (HIV) infection
• Established diagnosis of hepatitis B viral infection at the time of screening or positive for hepatitis B surface antigen (HBsAg) at the time of screening. Participants who have gained immunity for hepatitis B virus infection after vaccination (participants who are HBsAg negative, hepatitis B surface antibody [HBsAb] positive, and hepatitis B core antibody [HBcAb] negative are eligible for the study). Participants with positive HBcAb are eligible for the study only if hepatitis 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 RNA is negative.
• On current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis, or hepatic failure, or has evidence of liver disease as indicated by persistent (confirmed by repeated tests ≥2 weeks apart) elevated transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) more than 3 times the upper limit of normal [ULN] during the screening period)
• 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 abnormal value is detected at screening, a repeat test should be performed to confirm the abnormality. Only if the repeat test confirms the abnormality would the participant be categorized as a screen failure. eGFR will be calculated using the Modification of Diet in Renal Disease (MDRD) equation in adult participants and 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, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, or prurigo nodularis and also have asthma
• Do not change or stop corticosteroid medicine or other asthma medicine without talking to the investigators. This may cause other symptoms that were controlled by the corticosteroid medicine or other asthma medicine to come back. "
• Severe concomitant illness (es) that, in the investigator's judgment, would adversely affect the participant's participation in the study. Examples include but are not limited to short life expectancy, uncontrolled diabetes, cardiovascular conditions (e.g., NYHA Class III or IV cardiac failure), severe renal conditions (e.g., severe nephrotic syndrome), hepatobiliary conditions (e.g., Child-Pugh class B or C), neurological conditions (e.g., demyelinating diseases), active major autoimmune diseases (e.g., lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), other severe endocrinologic, gastrointestinal, metabolic, pulmonary, or lymphatic diseases. The specific justification for participants excluded under this criterion will be noted in study documents (chart notes, case report forms [CRF].
• History of malignancy within 5 years prior to screening, except completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal 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 laboratory abnormalities at screening that, in the opinion of the investigator, suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study participant as a result of his/her participation in this clinical trial, may make participant's participation unreliable, or may interfere with study assessments. The specific justification for participants excluded under this criterion 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 breastfeed during the study
• Heterosexual women of childbearing potential who are unwilling to practice highly effective 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 effective contraceptive measures include:
  • Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation 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 be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
• Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. ‡Periodic abstinence (calendar, symptom-thermal, post-ovulation methods), withdrawal (coitus interrupts), spermicides only, and lactation amenorrhea method are not acceptable methods of contraception. Female condom 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 esophagus using endoscopic, Savary or other kind of dilators will be allowed during the treatment with Dupilumab.