Clinical trial NCT06352073: Dupilumab for Eosinophilic Esophagitis With Severe Strictures
Official title: Dupilumab for Eosinophilic Esophagitis With Severe Strictures (DESTRICT Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Eosinophilic Esophagitis
EoE
Keywords: EoE
Stricture
dupilumab
Eosinophilic Esophagitis
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
name: Sanofi
First posted: 2024-04-08
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine how well an FDA-approved drug, dupilumab, works to treat patients with severe strictures and active Eosinophilic Esophagitis (EoE). This is an open-label study, meaning everyone in the study will receive dupilumab.

Participants will have a screening visit where they will complete surveys and undergo an endoscopy (EGD). Blood and biopsies (small tissue samples) will also be collected. If eligible and enrolled into the study, participants will receive weekly subcutaneous (under the skin) injections of dupilumab for 52 weeks (one year). The first dose of dupilumab will be administered at the week 1 visit by a clinician and participants will receive training on how to self-administer the remaining doses.

Participants will return for study visits every at weeks 4, 8, 12, 18, 24, 30, 36, 44, and 52. During these visits, vital signs (temperature, heart rate, etc.) will be collected and participants will complete surveys. During visits at week 12, 24, and 52, blood will be collected and an endoscopy with biopsy will be performed.

At 64 weeks (12 weeks after the last dose of dupilumab), participants assigned male at birth (AMAB) will be contacted about their / their partner's pregnancy status and participants assigned female at birth (AFAB) may be asked to come for an in-person visit to complete a urine pregnancy test.

Detailed description: This research study aims to learn how well an FDA-approved drug called dupilumab works in treating patients with Eosinophilic Esophagitis (EoE) and severe strictures (esophageal narrowing).

This is an open-label study, which means everyone enrolled will receive dupilumab. Dupilumab is a weekly injection, administered using a needle under the skin (subcutaneous injection). Dupilumab is already approved by the FDA for treating EoE.

Participants will be part of the study for approximately 64 weeks. In-person study visits will occur at specific intervals. Study Visits will happen at the beginning of the study (screening) and weeks 1, 4, 8, 12, 18, 24, 30, 36, 44, and 52.

Upper Endoscopies are performed at screening and weeks 12, 24, and 52 (or if participation ends early).

Pregnancy Status Check: 12 weeks after the last dose of dupilumab, participants will be contacted about their pregnancy status.

* Assigned Male at Birth (AMAB) participants may receive a phone call.
* Assigned Female at Birth (AFAB) participants may return for an in-person visit to complete a urine pregnancy test.

Study Procedures: What Participants Can Expect

1. Consent: Participants will review the study with the study team and have an opportunity to ask questions. If they decide to participate, they will sign a consent form.
2. Screening Procedures: These ensure eligibility for the study and include:

   * Answering questions about demographics and medical history.
   * A physical exam (checking vital signs like temperature, blood pressure, heart rate, and weight).
   * Reviewing medications.
   * Completing surveys about EoE symptoms, feelings, and quality of life.
   * Providing a blood sample.
   * Completing a urine pregnancy test (if applicable).
   * Undergoing an upper endoscopy (EGD) using a flexible, lighted tube to examine the stomach, small intestine, and esophagus. Sedation may be used during the procedure. During the EGD, tissue samples (biopsies) will be taken. If the participant has narrowing in their esophagus (a stricture) that needs to be stretched (dilated) may also be dilated during the procedure.
3. Enrollment visit (Week 1): Once eligibility is confirmed, participants will return to clinic to receive their first dose of dupilumab. At this visit, participants will:

   * Complete surveys about EoE symptoms, feelings, and quality of life
   * Check vital signs (temperature, blood pressure, respiratory rate, heart rate, and weight).
   * Provide a blood sample.
   * Complete a urine pregnancy test (if applicable)
   * Discuss lifestyle considerations that should be followed (birth control methods, medications, and diet)
   * Review medications and any new symptoms or medical history.
   * A health care provider will give the first dose of dupilumab and teach participants (and/or their caregivers) how to administer the medication at home.
   * Receive dupilumab to take home and instructions for giving the medication weekly.
4. Throughout the 1-year dosing period of the study, participants (and/or their caregivers) will continue to inject dupilumab at home each week and complete a dosing diary. Participants will come to clinic at weeks 4, 8, 12, 18, 24, 30, 36, 44, and 52. Procedures at these visits include:

   * Completing surveys about EoE symptoms, feelings, and quality of life
   * Vital signs (temperature, blood pressure, respiratory rate, heart rate, and weight).
   * Providing a blood sample.
   * Completing a urine pregnancy test (if applicable)
   * Discussing lifestyle considerations that should be followed (birth control methods, medications, and diet)
   * Reviewing medications and any new symptoms or medical history.
   * During week 12, 24, and 52 (or at the end of the study), there will also be an EGD with biopsies and dilation (if necessary).
   * Returning all used and unused dupilumab to the clinic.
   * Receive dupilumab to take home and instructions for giving the medication weekly.

5.12 weeks after the last dose of dupilumab, participants will be contacted about their pregnancy status.

* Assigned Male at Birth (AMAB) participants may receive a phone call.
* Assigned Female at Birth (AFAB) participants may return for an in-person visit to complete a urine pregnancy test.

Eligibility criteria: Requirements to be eligible for the study:

* Age 16 and older.
* Diagnosis of EoE (per 2018 AGREE consensus guidelines)
* Currently active EoE (defined as ≥15 eos/hpf \[eosinophils per high power field\]) based on samples taken from the screening endoscopy.
* Prior intolerance to or histologic non-response (defined as a peak esophageal eosinophil count of ≥15 eos/hpf) to proton pump inhibitors (PPI) and topical corticosteroids (tCS).
* For PPI, this must be after 8 weeks or more of treatment of at least 40mg daily of any of the approved medications.
* For tCS, this must be after 8 weeks or more of treatment of at least 2mg daily for budesonide or 1760 mcg daily for fluticasone).
* One of the following specific EoE features: 1) a narrow esophagus where a standard adult endoscope would not fit or 2) 4 or more prior esophageal dilations (stretching procedures), with at least 2 dilations reported within one year.
* Willing to follow certain lifestyle considerations during the study including:
* No diet changes,
* No changes in PPI medication dose,
* No topical/swallowed (tCS) or systemic steroids for add-on EoE therapy,
* Use highly effective birth control methods.
* Weigh at least 40kg (about 89 pounds or more).

Reasons a participant could be excluded:

* Other eosinophilic gastrointestinal (GI) disease including:

  * Eosinophilic gastritis,
  * Eosinophilic enteritis,
  * Eosinophilic colitis,
  * Hypereosinophilic syndrome.
* Recent steroid use (systemic or swallowed/topical corticosteroid within 4 weeks prior to the screening endoscopy).
* Recent use of dupilumab (Dupixent) (within 6 months of screening).
* Prior allergic reaction to dupilumab or its components, or dupilumab intolerance.
* Recent use of other biologic medications (within either 6 months or 5 half-lives, whichever is longer). Examples of biologic medications include:

  * mepolizumab (Nucala),
  * reslizumab (Cinqair, Cinqaero),
  * benralizumab (Fasenra),
  * cendakimab,
  * tezepelumab (Tezspire),
  * barzolvolimab, etc.
* Prior esophageal resection (surgery to remove the esophagus).
* Participants taking blood thinners (such as coumadin, warfarin, heparin, etc.) who are unable to stop taking them for a brief period prior to EGD (as required by normal clinical practice).
* Recent vaccination with a live (attenuated) vaccine (within 4 weeks of screening). Live vaccines include:

  * Chickenpox (varicella),
  * FluMist and Intranasal influenza,
  * Measles (rubeola),
  * Mumps,
  * Rubella,
  * Oral polio,
  * Oral typhoid,
  * Smallpox (vaccinia),
  * Yellow fever,
  * Bacille Calmette-Guerin
  * Rotavirus
  * Combination vaccines of any of the above.
* Study doctor's determination that it would not be medically safe to complete an EGD.
* Inability to read or understand English.
* Currently pregnant or breastfeeding.
* Currently in screening or eligible for another study of dupilumab (Dupixent).

Primary outcomes:
measure: Histologic Response to Dupilumab
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in Minimum Esophageal Caliber
timeFrame: 24 weeks
measure: Decrease in Number of Dilations
timeFrame: 52 weeks
measure: Change in Endoscopic Severity
timeFrame: 24 weeks
measure: Change in Histologic Severity
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Evan S Dellon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: