Clinical Trials

Inclusion Criteria: 

Age

• Participant must be ≥ 18 years of age inclusive, at the time of signing the informed consent.

Type of participant and disease characteristics

• A documented diagnosis of EoE by endoscopic biopsy prior to screening, as demonstrated by intraepithelial eosinophilic infiltration (peak cell count ≥ 15 Eos/HPF] from at least one esophageal region and performed after at least 8 weeks of treatment with a high-dose PPI regimen. If the participant discontinued PPI therapy, the biopsy must have been performed within 2 weeks of the date of discontinuation. If a prior (historical) endoscopic biopsy meeting these criteria is not available (or no prior biopsy is available), participants who meet other clinical and laboratory eligibility criteria will undergo treatment with a high-dose PPI regimen for at least 8 weeks before their baseline endoscopy/biopsies. Note: If the participant is already using an acceptable high-dose PPI regimen at the time of the screening visit, the baseline endoscopy may be scheduled at any point during the screening period after 8 weeks of treatment have been documented.
• Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration (peak cell count ≥ 15 Eos/HPF) in at least 2 of the 3 biopsied esophageal regions (proximal, mid, or distal).
• History (by participant report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening.
• At least 4 episodes of dysphagia in the 2 weeks prior to baseline, documented via eDiary, at least 2 of which require liquids, coughing or gagging, vomiting, or medical attention to obtain relief.
• Completed at least 11 of 14 days of DSQ eDiary data entry in the 2 weeks prior to baseline.
• Baseline DSQ score ≥ 10. Refer Appendix 10.11 Section 10.11.1.

Weight

• Body weight ≥ 40 kg. Sex, contraceptive/barrier method and pregnancy testing requirements/breastfeeding.
• All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:
  • Male participants:
    • Male participants are eligible to participate if they agree to the following during the study treatment period and for at least 12 weeks after the last administration of study intervention:
      • Refrain from donating or cryopreserving sperm PLUS, either:
        • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent; OR
        • Must agree to use contraception/barrier as detailed below:
          • A male condom; the participant should also be advised of the benefit for a female partner to use a highly effective method of contraception as described in Appendix 4 Contraceptive and Barrier Guidance (Section 10.4) as a condom may break or leak when having sexual intercourse with a WOCBP who is not currently pregnant.
      •  
  • Female participants:
    • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
      • Is a woman of nonchildbearing potential as defined in Appendix 4 Contraceptive and barrier guidance (Section 10.4); OR
      • Is a WOCBP and agrees to use a contraceptive method that is highly effective, with a failure rate of < 1%, as described in Appendix 4 Contraceptive and barrier guidance (Section 10.4) during the study intervention period and for at least 12 weeks after the last administration of study intervention. A WOCBP must have a negative highly sensitive pregnancy test at screening (serum) and on Day 1 (urine) before the first administration of study intervention, see Section 8.3.6 Pregnancy testing. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

Informed Consent

• Capable of giving signed informed consent as described in Appendix 1 (Section 10.1.3) of the protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Other inclusion criteria.
• Able to understand and complete study-related questionnaires.
• Willing and able to comply with site visits and study-related procedures.

Exclusion Criteria:

Medical conditions

• Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Note: Participants with eosinophilic gastroenteritis based on medical history 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.
• Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening.
• History of bleeding disorders or esophageal varices that, in the opinion of the Investigator, would put the participant at undue risk for significant complications from an endoscopy procedure.
• 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 participants with short life expectancy, participants with uncontrolled diabetes (hemoglobin A1c ≥ 9%), participants with cardiovascular conditions (eg, Class III or IV cardiac failure according to the New York Heart Association classification), severe renal conditions (eg, participants on dialysis), hepato-biliary conditions (eg, Child-Pugh class B or C), neurological conditions (eg, demyelinating diseases), autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid arthritis, etc), other severe endocrinological, gastrointestinal, metabolic, pulmonary, psychiatric, or lymphatic diseases. The specific justification for participants excluded under this criterion will be noted in study documents (chart notes, CRF, etc).
• Participant with active TB or nontuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded from the study unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing will be performed on a country-by-country basis, according to local guidelines if required by regulatory authorities or ethics boards, or if TB is suspected by the Investigator.
• Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the screening visit (Visit 1) or during the screening period. Note: A participant may be rescreened after the infection resolves.
• History of HIV infection or positive HIV 1/2 serology at the screening visit (Visit 1).
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the screening visit (Visit 1) or during the screening period.
• Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune compromised status, as judged by the Investigator.
• Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
• Known or suspected alcohol and/or drug abuse.
• Participant with any other medical or psychological condition including relevant laboratory or electrocardiogram 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 (chart notes, CRF, etc).

Prior/concomitant therapy

• Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline.
• 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 treatment 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.
• Initiation, discontinuation, or change in the dosage regimen of 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.
• Initiation or change of a food elimination diet regimen or reintroduction 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.
• Treatment with SLIT.
• Treatment with OIT within 6 months prior to screening visit (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, IFN-γ, Janus kinase inhibitors, azathioprine, and methotrexate;
  • Note: The use of a corticosteroid as a part of the anesthetic preparation used during each endoscopy procedure is allowed.
• Planned or anticipated major surgical procedure during the participant's participation in this study.
• Participant who has taken biologic therapy/systemic immunosuppressant/immunomodulator within 4 weeks before the screening visit (Visit 1) or 5 half-lives, whichever is longer.
• Treatment with a live (attenuated) vaccine within 4 weeks before the screening visit (Visit 1):
  • NOTE: For participants who have vaccination with live, attenuated vaccines planned during the course of the study (based on national vaccination schedule/local guidelines), it will be determined, after consultation with a physician, whether the administration of vaccine can be postponed until after the end-of-study, or preponed to before the start of the study without compromising the health of the participant:
    • Participant for whom administration of live (attenuated) vaccine can be safely postponed would be eligible to enroll into the study;
    • Participants who have their vaccination preponed can enroll in the study only after a gap of 4 weeks following administration of the vaccine.
• Either intravenous immunoglobulin therapy and/or plasmapheresis within 4 weeks before the screening visit (Visit 1).
• Use of any prohibited medications (Section 6.9) and procedures during screening period or planned use during screening or study treatment period.

Prior/concurrent clinical study experience

• Current participation to any clinical trial of an investigational drug or device or participation within 3 months before the screening visit or 5 half-lives of the investigational compound, whichever is longer.
• Participation in prior dupilumab clinical study or participants currently treated or have been treated with commercially available dupilumab or contraindicated to dupilumab per local labelling.

Diagnostic assessments

• Participant with any of the following result at the screening visit (Visit 1): - Positive (or indeterminate) Hepatitis B surface antigen (HBsAg) or, - Positive total HBcAb confirmed by positive HBV DNA or, - Positive HCVAb confirmed by positive HCV RNA.

Other exclusions

• Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
• Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with Section 1.61 of the ICH GCP Ordinance E6).
• Any specific situation during study implementation/course that may raise ethics considerations.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/23/23. Questions regarding updates should be directed to the study team contact.