An Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE)

NCT03029091 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2015-9021U54AI117804
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the safety and effectiveness of Losartan potassium in subjects with eosinophilic esophagitis (EoE) including those with a connective tissue disorder (CTD) and those without a CTD.

Conditions

Eosinophilic Esophagitis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Peak Eosinophil Count

  Peak esophageal eosinophil counts were obtained at baseline and 16 weeks. Change in peak eosinophil count is defined as peak count at 16 weeks minus peak count at baseline. A reduction (negative change) in peak count indicates improvement. Peak count is defined as the highest count between the distal and proximal esophageal eosinophil counts.

  Baseline, 16 weeks

• Number of Serious and Grade 3 or Higher Adverse Events

  The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20

  20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up)

Secondary Outcomes (5)

• Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks

  16 weeks

• Change From Baseline in Total Histology Scoring System

  Baseline, 16 weeks

• Change From Baseline in Total Endoscopic Reference Score

  Baseline, 16 weeks

• Change From Baseline in PEESS V2.0

  Baseline,16 weeks

• Change From Baseline in PedsQL EoE

  Baseline, 16 weeks

Study Arms (3)

EoE +/- CTD

EXPERIMENTAL

Participants with EoE with and without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks

Drug: Losartan Potassium

EoE + CTD

EXPERIMENTAL

Participants with EoE with CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks

Drug: Losartan Potassium

EoE - CTD

EXPERIMENTAL

Participants with EoE without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks

Drug: Losartan Potassium

Interventions

Losartan Potassium DRUG

Losartan potassium

Also known as: Losartan

EoE + CTD; EoE +/- CTD; EoE - CTD

Eligibility Criteria

• Age: 5 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed consent/assent
• Confirmed, active EoE (at Screening or within 12 weeks prior to enrollment)
• Does or does not have diagnosis of a connective tissue disorder (CTD)
• Has been on a high dose of proton pump inhibitor (PPI) for at least 8 weeks prior to a diagnostic endoscopy of EoE without histologic resolution (i.e., ≥ 15 eosinophils/HPF).
• Maintain the same diet, swallowed steroid and PPI therapies throughout the duration of the study
• Female participants must be either:
• Of non-childbearing potential (pre-menarchal or surgically sterile with documentation). OR
• Have a negative urine pregnancy test at screening and at each monthly study visit.

You may not qualify if:

• Any past or planned cardiac surgery.
• An aortic root Z-score ≥ 3.0 on a previous echocardiogram.
• Intolerance to Losartan
• A mean blood pressure measurement (both systolic and diastolic) at screening that is below the 2nd percentile for his/her age
• Renal dysfunction
• Another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic syndrome, Churg Strauss vasculitis, eosinophilic granuloma, or a parasitic infection).
• A diagnosis of hepatic insufficiency (e.g., liver failure, history of liver transplantation or persistent liver transaminase elevation).
• A history of abnormal gastric or duodenal biopsy or documented gastrointestinal disorders (e.g., Celiac Disease, Crohn's disease or Helicobacter pylori infection), not including chronic gastritis, chronic duodenitis, mucosal eosinophilia or other eosinophilic gastrointestinal disorders (EGIDs).
• Use of anti-immunoglobulin (Ig)E monoclonal antibody (mAb), anti-tumor necrosis factor (TNF) mAb, anti-IL-5 agents, or anti-IL-13 within 6 months prior to study entry
• Use of methotrexate, cyclosporine, interferon α, or other systemic immunosuppressive or immunomodulating agents within 3 months prior to the screening visit.
• A stricture during endoscopy procedure that prevents passage of the endoscope
• Taking or is planning to take an angiotensin receptor blocker (ARB), angiotensin-converting enzyme inhibitor (ACEI), beta blocker (BB), or calcium-channel blocker therapy at the screening visit or at any time during the study or has been taking any of these medications for 3 months prior to the screening visit.
• Taking or planning to take hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, rifampin, or fluconazole.
• Taking or planning to take potassium supplements or salt substitutes containing potassium.
• A female participant who is pregnant or nursing or, if of childbearing potential, is not using a medically accepted, effective method of birth control (e.g., condom, oral/injectable/subcutaneous contraceptive, intrauterine device, or sexual abstinence).

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Office of Rare Diseases (ORD): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (3)

University of California, San Diego

La Jolla, California, 92093, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Links

• Study information on the Consortium for Eosinophilic Gastrointestinal Disorders (CEGIR) website

MeSH Terms

Conditions

Eosinophilic Esophagitis

Interventions

Losartan

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Marc E. Rothenberg, MD, PhD
• Organization: Cincinnati Children's Hospital Medical Center

marc.rothenberg@cchmc.org

513 636-7177

Study Officials

• Marc E Rothenberg, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is an open-label study which means that all participants receive the study medicine.

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: May 23, 2017
• Primary Completion: July 22, 2019
• Study Completion: August 22, 2019
• Last Updated: September 9, 2020
• Results First Posted: August 10, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)