Regeneron

Principal Investigator: Kathryn Peterson
Keywords: R668-EE-1324: A Randomized, Double-Blind, Parallel, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Dupilumab in Adult Patients with Active Eosinophilic Esophagitis. Department: Gastroenterology
IRB Number: 00080657 Co Investigator: Kathleen Boynton
Specialty: Gastroenterology
Sub Specialties: Esophageal Diseases
Recruitment Status: Recruiting

Contact Information

Shannah Aleiwe
shannah.aleiwe@hsc.utah.edu
801-587-9050

Brief Summary

The primary objective of the study is to assess the clinical efficacy of repeat subcutaneous (SC) doses of dupilumab, compared with placebo, to relieve symptoms in adult patients with active, moderate to severe eosinophilic esophagitis (EoE). 
 
The secondary objectives of the study are: 
To assess the safety, tolerability, and immunogenicity of SC doses of dupilumab in adult patients with active,  moderate to severe EoE
To assess the effect of dupilumab on esophageal eosinophilic inflammation
To evaluate the pharmacokinetics (PK) of dupilumab in adult patients with EoE

Inclusion Criteria

1. Male or female, 18 to 65 years old

2. Documented diagnosis of EoE by endoscopy prior to screening

Note: Must include a demonstration of intraepithelial eosinophilic infiltration (peak cell

count ≥15 eosinophils/high power field [eos/hpf] [400X]) from esophageal biopsy

specimens from endoscopy performed no more than 2 weeks after at least 8 weeks of treatment with high

dose (or twice-daily dosing) proton pump inhibitors (PPIs)

3. History (by patient report) of on average at least 2 episodes of dysphagia (with intake of

solids off anti-inflammatory therapy) per week in the 4 weeks prior to screening and on

average at least 2 episodes of documented dysphagia per week in the weeks between

screening and baseline; dysphagia is defined as trouble swallowing solid food, or having

solid food stick, by patient report

4. Must remain on a stabilized diet for at least 6 weeks prior to screening and 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

5. SDI PRO score ≥5 at screening and baseline

6. Documented history of or presence of 1 or more of  any of the following: allergic disease (eg, allergic

asthma, allergic rhinitis, AD, or food allergies), peripheral eosinophil counts ≥0.25 GI/L,

or serum total Immunoglobulin E (IgE) ≥100 kU/L

7. Willing and able to comply with all clinic visits and study-related procedures

8. Able to understand and complete study-related questionnaires

9. Provide signed informed consent

10. Endoscopy with photographs performed at screening, with a demonstration of intraepithelial eosinophilic

infiltration (peak cell count ≥15 eos/hpf) in at least 2 of the 3 biopsied esophageal regions

(proximal, mid, or distal)

Exclusion Criteria

1. Prior participation in a dupilumab (anti-IL-4R) clinical trial

2. Other causes of esophageal eosinophilia or the following diseases: hypereosinophilic

syndromes, Churg-Strauss vasculitis, and eosinophilic gastroenteritis

3. History of achalasia, active Helicobacter pylori infection, Crohn’s disease, ulcerative

colitis, celiac disease, and prior esophageal surgery prior to screening

4. Any esophageal stricture unable to be passed with a standard, diagnostic, adult

(9 to10 mm) upper endoscope or any critical esophageal stricture that requires dilation at

screening

5. History of bleeding disorders or esophageal varices

6. Use of chronic aspirin, nonsteroidal agents, or anti-coagulants within 2 weeks prior to

screening. Patients should not stop these agents solely to become eligible for entry into

this study

7. Treatment with an investigational drug within 2 months or within 5 half-lives (if known),

whichever is longer, prior to screening

8. Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids

within 6 weeks prior to screening
9. Use of inhaled or nasal corticosteroids within 3 months prior to screening and during the study, except stable dose for at least 3 months prior to screening biopsy, which cannot be changed during the study
10. Treatment with oral immunotherapy (OIT) within 6 months prior to screening
11. Allergen immunotherapy (sublingual immunotherapy [SLIT] and/or subcutaneous
immunotherapy [SCIT], unless on stable dose for at least 1 year prior to screening
12. The following treatments within 3 months before the screening visit, or any condition
that, in the opinion of the investigator, is likely to require such treatment(s) during the
3 months of study treatment:
Systemic immunosuppressive/immunomodulating drugs (eg, omalizumab, cyclosporine,
mycophenolate-mofetil, interferon-gamma [IFN-γ], Janus kinase inhibitors, azathioprine,
methotrexate, leukotriene inhibitors [except stable dose for at least 3 months prior to
screening], etc.)
13. Diagnosed with active parasitic infection; suspected parasitic infection, unless clinical
and (if necessary) laboratory assessments have ruled out active infection before
randomization
14. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or
antifungals within 1 month prior to screening
15. Use of oral antibiotics/anti-infectives within 2 weeks prior to screening
16. Known or suspected immunosuppression, including history of invasive opportunistic
infections (eg, tuberculosis, non-tuberculous mycobacterial infections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections suggesting an
immune-compromised status, as judged by the investigator
17. Known history of human immunodeficiency virus (HIV) infection
18. Positive or indeterminate hepatitis B surface antigen (HBsAg) or hepatitis C antibody at
screening
19. Elevated transaminases (alanine aminotransferase [ALT] and/or aspartate
aminotransferase [AST]) more than 3 times the upper limit of normal (>3 x upper limit of
normal [ULN]) at screening
20. History of malignancy within 5 years prior to screening, except completely treated in situ
carcinoma of the cervix and completely treated and resolved non-metastatic squamous or
basal cell carcinoma of the skin
21. History of patient-reported alcohol or drug abuse within 6 months prior to screening
22. 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 patient as a result of
his/her participation in this clinical trial, may make patient’s participation unreliable, or
may interfere with study assessments. The specific justification for patients excluded
under this criterion will be noted in study documents (chart notes, case report form
[CRF], etc.)
23. Severe concomitant illness(es) that, in the investigator’s judgment, would adversely
affect the patient’s participation in the study.
24. Planned or anticipated use of any prohibited medications and procedures (as detailed in
section 5.5) during study treatment
25. Treatment with a live (attenuated) vaccine within 3 months prior to screening
26. Patient or his/her immediate family is a member of the investigational team.
27. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed
during the study
28. Women unwilling to use adequate birth control, if of reproductive potential* and sexually
active. Adequate birth control is defined as agreement to consistently practice an
effective and accepted method of contraception throughout the duration of the study and
for 120 days after last dose of study drug. These include: hormonal contraceptives,
intrauterine device, or double barrier contraception (ie, condom + diaphragm), or male
partner with documented vasectomy.
* For females, menopause is defined as at least 12 consecutive months without menses;
if in question, a follicle stimulating hormone (FSH) of ≥25 U/mL must be
documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must
be documented, as applicable; if documented, women with these conditions are not
required to use additional contraception.