Clinical trial NCT05084963: A Study to Assess the Efficacy, Safety and Tolerability of IRL201104 in Adults With Active Eosinophilic Esophagitis
Official title: A Phase 2a, Double-blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy, Safety, and Tolerability of IRL201104 in Adult Participants With Active Eosinophilic Esophagitis (EoE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eosinophilic Esophagitis
Keywords: EoE
Lead sponsor: Revolo Biotherapeutics
Sponsor class: INDUSTRY
First posted: 2021-10-20
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to asses the efficacy, safety and tolerability of repeat doses of IRL201104 in Adult Participants with Active Eosinophilic Esophagitis (EoE)


Eligibility criteria: Inclusion Criteria:

1. Age 18 to 75 years old, inclusive, at the time of signing the informed consent form.
2. Documented diagnosis of EoE by endoscopy prior to screening. Note: Must include a demonstration of intraepithelial eosinophilic infiltration (peak cell count ≥ 15 eos/hpf \[400×\]) from esophageal biopsy specimens from endoscopy.
3. History (by participant 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 during any 2 consecutive weeks (qualifying period) between screening and baseline; dysphagia is defined as trouble swallowing solid food, or having solid food stick, by participant report; and completed the DSQ on ≥ 70% of days during the qualifying period prior to baseline (Visit 1).
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. Must be willing and able to continue any dietary therapy and/or medical regimens (including gastric acid suppression) in effect at the screening visit. There should be no change to these regimens during the study participation.
6. Willing and able to comply with all clinic visits and study-related procedures.
7. Able to understand and complete study-related questionnaires.
8. Provide signed informed consent.
9. Esophagogastroduodenoscopy (EGD) with photographs performed at screening (qualifying EGD), 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 an IRL201104 clinical study.
2. Has any current disease of the gastrointestinal tract (aside from EoE) that may impact, in the investigator's opinion, the patient's EoE disease status. This includes, but not limited to: eosinophilic gastritis, eosinophilic enteritis, eosinophilic duodenitis, eosinophilic colitis, or proctitis; inflammatory bowel disease; or celiac disease.
3. Has other causes of esophageal eosinophilia or the following diseases: hypereosinophilic syndromes, Churg-Strauss vasculitis (eosinophilic granulomatosis with polyangiitis), or peripheral blood absolute eosinophil count of \> 1500 eosinophils/μL.
4. Has presence of oral or esophageal mucosal infection of any type.
5. Has any condition affecting the esophageal mucosa or altering esophageal motility other than EoE.
6. History of achalasia, active Helicobacter pylori infection, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery (with the exception of a surgical repair of an EoE complication).
7. Any esophageal stricture unable to be passed with a standard, diagnostic, adult (9 to 10 mm) upper endoscope or any critical esophageal stricture that requires dilation at screening; or dilation within 2 months prior to screening.
8. On a pure liquid diet or any mouth or dental condition that prevents normal eating.
9. Has initiated, discontinued, or changed dosage regimen of PPIs within the 4 weeks prior to the qualifying EGD, between the qualifying EGD and baseline visit (Visit 1), or anticipates changes in the use of PPI during the study. PPI must remain constant throughout the study.
10. History of bleeding disorders or esophageal varices.
11. Use of anticoagulants within 2 weeks prior to screening. Participants should not stop these agents solely to become eligible for entry into this study.
12. Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening.
13. Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids within 6 weeks prior to screening.
14. Treatment with oral immunotherapy (OIT) within 6 months prior to screening.
15. Allergen immunotherapy (sublingual immunotherapy \[SLIT\] and/or subcutaneous immunotherapy \[SCIT\]), unless on a stable dose for at least 1 year prior to screening.
16. 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 study:

    Systemic immunosuppressive/immunomodulating drugs (eg, omalizumab, cyclosporine, mycophenolate-mofetil, interferon \[IFN\]γ, Janus kinase inhibitors, azathioprine, methotrexate, and other biologics that are ongoing \[eg, dupilumab, benralizumab, mepolizumab, or vedolizumab\]).
17. Diagnosed with active parasitic infection; or suspected parasitic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomization.
18. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 1 month prior to screening.
19. Use of oral antibiotics/anti-infectives within 2 weeks prior to screening.
20. 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 immunocompromised status, as judged by the investigator.
21. Known history of human immunodeficiency virus (HIV) infection.
22. Positive or indeterminate hepatitis B surface antigen (HBsAg) or hepatitis C antibody at screening.
23. Moderate or severe renal impairment (eGFR \<60 mL/min/1.73 m2) or end stage renal disease.
24. Elevated transaminases (alanine aminotransferase \[ALT\] and/or aspartate aminotransferase \[AST\]) \> 3 times the upper limit of normal (ULN) at screening.
25. History of malignancy within 5 years prior to screening, except completely treated in situ carcinoma of the cervix and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
26. 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 participant as a result of his/her participation in this clinical study, may make the 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 (eg, chart notes, electronic case report form). These may include participant-reported alcohol or drug abuse and severe concomitant illness(es).
27. Planned or anticipated use of any prohibited medications and procedures (as described in the exclusion criteria) during study treatment.
28. Treatment with a live (attenuated) vaccine within 3 months prior to screening and/or treatment of a killed vaccine within 30 days prior to screening, until the end of the study with the exception of a coronavirus disease of 2019 (COVID-19) vaccine, as described in Section 9.2.1.
29. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
30. 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 30 days after the last dose of study treatment. These include: hormonal contraceptives, intrauterine device, or double barrier contraception (ie, condom and diaphragm), or male partner with documented vasectomy.

    * For females, menopause is defined as at least 12 consecutive months without menses; to include laboratory confirmation of post-menopausal status (ie, a follicle stimulating hormone (FSH) of 2.25 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.

Primary outcomes:
measure: Change From Baseline in the Peak Esophageal Intraepithelial Eosinophil Count at Week 4 (Mean)
timeFrame: 4 weeks
Secondary outcomes:
measure: Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline.
timeFrame: 4 weeks
measure: Percent of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of < 15 Eos/Hpf (Week 4)
timeFrame: 4 weeks
measure: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf)
timeFrame: 4 weeks
measure: Treatment Emergent Adverse Events (TEAE)
timeFrame: 8 weeks
measure: Safety Laboratory Data: Biochemistry
timeFrame: 8 weeks
measure: Safety Laboratory Data: Coagulation
timeFrame: 8 weeks
measure: Safety Laboratory Data: Hematology Panel
timeFrame: 8 weeks
measure: Safety Laboratory Data: Urinalysis Panel
timeFrame: 8 weeks
measure: 12-Lead ECG
timeFrame: 8 weeks
measure: Physical Exam
timeFrame: 8 weeks
measure: Vital Signs
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Revolo Investigational Site
state: Arkansas
city: Murrieta
country: United States
facility: Revolo Investigational Site
state: California
city: Centennial
country: United States
facility: Revolo Investigational Site
state: Colorado
city: New Port Richey
country: United States
facility: Revolo Investigational Site
state: Florida
city: Orlando
country: United States
facility: Revolo Investigational Site
state: Florida
city: Sandy Springs
country: United States
facility: Revolo Investigational Site
state: Georgia
city: Iowa City
country: United States
facility: Revolo Investigational Site
state: Iowa
city: Crowley
country: United States
facility: Revolo Investigational Site
state: Louisiana
city: Marrero
country: United States
facility: Revolo Investigational Site
state: Louisiana
city: Boston
country: United States
facility: Revolo Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Revolo Investigational Site
state: Massachusetts
city: Farmington Hills
country: United States
facility: Revolo Investigational Site
state: Michigan
city: Great Neck
country: United States
facility: Revolo Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Revolo Investigational Site
state: North Carolina
city: Durham
country: United States
facility: Revolo Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Revolo Investigational Site
state: North Carolina
city: Mentor
country: United States
facility: Revolo Investigational Site
state: Ohio
city: Chattanooga
country: United States
facility: Revolo Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: Revolo Investigational Site
state: Tennessee
city: Baytown
country: United States
facility: Revolo Investigational Site
state: Texas
city: Harlingen
country: United States
facility: Revolo Investigational Site
state: Texas
city: Riverton
country: United States
facility: Revolo Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Revolo Investigational Site
state: Utah
Study officials:
affiliation: Senior Director, Revolo Biotherapeutics
name: Michael Weinreich, MD, PhD
role: STUDY_DIRECTOR
References: