EP-104IAR for EoE

(RESOLVE Trial)

Recruiting at 19 trial locations

Overseen By Pranali Ravikumar, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eupraxia Pharmaceuticals Inc.

Must not be taking: Antibiotics, Corticosteroids

Disqualifiers: Esophageal disease, Infections, Motility disorders, others

Compensation: Varies

Number of Visits: 8

Duration: 24-52 weeks

117 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EP-104GI (also known as EP-104IAR or Fluticasone Propionate) for adults with eosinophilic esophagitis (EoE), a condition that inflames the esophagus and can make swallowing painful. The study will assess the treatment's safety and effectiveness, with participants receiving it through a procedure involving the throat and stomach. Individuals struggling with EoE symptoms who can adhere to the study schedule might be suitable candidates. Participants will undergo several assessments, including questionnaires and biopsies, to track the treatment's effects over about a year. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in EoE treatment.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that recent use of disallowed medications or unwillingness to not use disallowed medications during the study is an exclusion criterion. It's best to discuss your current medications with the study team to see if they are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that EP-104GI, a treatment under study for eosinophilic esophagitis (EoE), appears safe. EP-104GI is a type of steroid called fluticasone propionate. Studies suggest it could be a safe and effective treatment with lasting benefits. So far, participants have generally tolerated the drug well, with no major safety issues reported.

These studies offer valuable insights, but as this is a new treatment, ongoing research will closely monitor its safety. As the trial progresses, more information will become available to help understand how well participants handle the treatment and any possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for EoE?

Researchers are excited about EP-104IAR for Eosinophilic Esophagitis (EoE) because it introduces a new approach to treatment. Unlike existing therapies like corticosteroids and dietary management, EP-104IAR is delivered through submucosal injections during an endoscopic procedure, potentially allowing for more direct and targeted relief. This method could offer a more efficient delivery of the medication directly to the esophagus, which might translate into quicker and more effective treatment outcomes. Additionally, the range of dosages being tested could help tailor treatment to individual needs, enhancing personalization in EoE management.

What evidence suggests that EP-104IAR might be an effective treatment for eosinophilic esophagitis?

Research has shown that EP-104GI could help treat eosinophilic esophagitis (EoE). This trial will evaluate various doses of EP-104GI to determine their effectiveness in relieving symptoms and improving the esophagus's condition. The treatment delivers fluticasone propionate, a type of steroid, directly into the esophagus, and appears safe and effective. Early results suggest that this method might offer longer-lasting symptom relief with fewer doses, making EP-104GI an exciting option for people with EoE. ^{1 3 6 7 8}

Who Is on the Research Team?

Mark Kowalski, MD PhD

Principal Investigator

Eupraxia Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with eosinophilic esophagitis (EoE) who can consent and follow the study plan. Women must test negative for pregnancy and use birth control. Excluded are those with other esophageal diseases, infections, severe swallowing disorders, risks from endoscopy or biopsy procedures, recent steroid contraindications, certain medication use, dietary changes or another trial participation.

Inclusion Criteria

For women of childbearing potential, a negative pregnancy test and willing to use a highly effective method of birth control until end of study

I have symptoms of EoE.

Willing and able to adhere to study-related procedures and visit schedule

Exclusion Criteria

Morning serum cortisol level ≤ 5 μg/dL (138 nmol/L)

I have previously participated in this study and received treatment.

Clinically significant abnormal laboratory values

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EP-104IAR during an esophagogastroduodenoscopy (EGD) procedure at the Baseline/Dosing visit. Safety, pharmacokinetics, and efficacy are evaluated through dose escalation and cohort expansion.

24-52 weeks

8-10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of dysphagia and odynophagia symptoms, and endoscopic and histologic evaluations.

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EP-104IAR

Trial Overview

The safety and effects of varying doses of EP-104IAR in adults with EoE are being tested. Up to 24 participants will receive the drug during an endoscopic procedure over about 32 weeks. The study includes blood/urine tests for safety monitoring and questionnaires on swallowing difficulties.

How Is the Trial Designed?

Group I: EP-104GI 96 mg Experimental Treatment 1 Intervention

16 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group II: EP-104GI 80 mg Experimental Treatment 1 Intervention

20 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group III: EP-104GI 8 mg Experimental Treatment 1 Intervention

8 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group IV: EP-104GI 64 mg Experimental Treatment 1 Intervention

16 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group V: EP-104GI 48 mg Experimental Treatment 1 Intervention

12 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group VI: EP-104GI 4 mg Experimental Treatment 1 Intervention

4 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group VII: EP-104GI 30 mg Experimental Treatment 1 Intervention

12 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group VIII: EP-104GI 20 mg Experimental Treatment 1 Intervention

8 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group IX: EP-104GI 160 mg Experimental Treatment 1 Intervention

20 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group X: EP-104GI 120 mg Experimental Treatment 1 Intervention

20 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group XI: EP-104GI Dose A or matching vehicle control Placebo Group 2 Interventions

20 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Group XII: EP-104GI Dose B or matching vehicle control Placebo Group 2 Interventions

20 submucosal injections of EP-104GI administered during an EGD procedure at the Baseline/Dosing visit.

Who Is Running the Clinical Trial?

Eupraxia Pharmaceuticals Inc.

Lead Sponsor

Trials

3

Recruited

410+

Published Research Related to This Trial

A comparison of adverse event reports (AERs) for mifepristone abortions from 2009 to 2010 revealed significant discrepancies, with Cleland et al. documenting 1530 cases while the FDA's FAERS reported only 664 total AERs.

The findings suggest that the FAERS system may be inadequate for accurately assessing the safety of mifepristone abortions, as it reported only a fraction of ongoing pregnancies (95) compared to Cleland's documentation (1158).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mifepristone Adverse Events Identified by Planned Parenthood in 2009 and 2010 Compared to Those in the FDA Adverse Event Reporting System and Those Obtained Through the Freedom of Information Act. Cirucci, CA., Aultman, KA., Harrison, DJ.[2022]

A meta-analysis of two clinical studies involving adolescents and adults with persistent asthma found that fluticasone furoate 100 µg once-daily (FF100) is non-inferior to fluticasone propionate 250 µg twice-daily (FP250) in improving lung function, as measured by trough forced expiratory volume in 1 second (FEV1).

Both FF100 and FP250 showed similar efficacy in enhancing lung function, indicating that FF100 can be an effective once-daily alternative for asthma maintenance treatment without significant differences in performance compared to the twice-daily FP250.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Meta-Analysis of the Efficacy of Once-Daily Fluticasone Furoate 100 µG Versus Twice-Daily Fluticasone Propionate 250 µG in Adolescents and Adults with Persistent Asthma. Tomlinson, R., Parks, D., Martin, A.[2018]

Fluticasone propionate, administered at 500 micrograms twice daily via Diskus and Diskhaler devices, significantly improved lung function and reduced asthma symptoms in 213 participants over 12 weeks, demonstrating its efficacy in treating mild-to-moderate asthma.

The treatment was well tolerated, with similar rates of adverse events across all groups, and fewer patients in the fluticasone groups withdrew due to lack of efficacy compared to the placebo group, indicating its effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diskus and diskhaler: efficacy and safety of fluticasone propionate via two dry powder inhalers in subjects with mild-to-moderate persistent asthma. Galant, SP., van Bavel, J., Finn, A., et al.[2018]

In a study involving 741 healthcare workers, the cell-based quadrivalent vaccine Flucelvax Tetra was found to have a high safety profile, with 99.8% of reported adverse events classified as not serious.

Out of 430 adverse events following immunization, only one was serious, and causality assessment indicated it was not linked to the vaccine, suggesting that Flucelvax Tetra is safe for use in healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study. Stefanizzi, P., De Nitto, S., Spinelli, G., et al.[2021]

In a study involving 1008 individuals vaccinated with the quadrivalent inactivated split-virion influenza vaccine (IIV4) during the 2020/21 season, the overall reporting rate of suspected adverse drug reactions (ADRs) was 7.84%, with the most common reactions being mild injection site reactions, myalgia, and headache.

No serious adverse events were reported, and the ADR rates were lower compared to the previous year's surveillance, reinforcing the safety profile of IIV4 and supporting public confidence in influenza vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced passive safety surveillance of a quadrivalent inactivated split virion influenza vaccine in Finland during the influenza season 2020/21. Syrkina, O., Inamdar, A., Wague, S., et al.[2022]

In 2012, Canada reported an adverse event following immunization (AEFI) rate of 10.1 per 100,000 population, showing a decline from 14.8 in 2005, indicating improved safety monitoring over time.

The majority of AEFI reports (94%-95%) were non-serious, primarily involving mild reactions such as site pain, rash, and fever, highlighting the overall good safety profile of vaccines administered in Canada.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canadian Adverse Events Following Immunization Surveillance System (CAEFISS): Annual report for vaccines administered in 2012. Law, BJ., Laflèche, J., Ahmadipour, N., et al.[2023]

In a study of 96 patients with severe asthma, treatment with fluticasone propionate at 1000 micrograms twice daily for 16 weeks significantly improved quality of life scores in areas such as physical functioning and general health compared to placebo.

These quality of life improvements were sustained over a subsequent year of open-label treatment, indicating that fluticasone propionate not only enhances pulmonary function but also has a lasting positive impact on patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone propionate improves quality of life in patients with asthma requiring oral corticosteroids. Okamoto, LJ., Noonan, M., DeBoisblanc, BP., et al.[2015]

In a study of patients treated with 5-FU for actinic keratosis, 58% reported adverse events, primarily including redness and inflammation (38%) and burning or pain (27%), indicating significant irritation associated with this treatment.

Compared to topical tacrolimus, which had only two reported call-backs related to medication issues, the higher call-back rate for 5-FU suggests that its irritation is more severe, highlighting the need for careful consideration of treatment options and patient education.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reasons for Patient Call-backs while being Treated with Topical 5-fluorouracil: A Retrospective Chart Review. Singh, R., Shah, MA., Feldman, SR.[2023]

Fluticasone propionate is a highly potent corticosteroid with a strong affinity for the glucocorticoid receptor, showing greater effectiveness than other corticosteroids like beclomethasone and budesonide in various in vitro tests.

It demonstrates significant anti-inflammatory effects, such as inhibiting mast cell activation and reducing eosinophil accumulation in the lungs, making it a powerful option for treating respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anti-inflammatory profile of fluticasone propionate. Johnson, M.[2019]

EP-104IAR, a sustained-release formulation of fluticasone propionate, was well tolerated in a study of 32 patients with knee osteoarthritis, showing no significant adverse effects on cortisol levels or safety margins.

Patients reported significant improvements in osteoarthritis symptoms that lasted for 8-12 weeks after a single 15 mg dose, indicating potential efficacy for further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of EP-104IAR (sustained-release fluticasone propionate) in knee osteoarthritis: A randomized, double-blind, placebo-controlled phase 1 trial. Malone, A., Price, J., Price, N., et al.[2022]

Fluticasone propionate (FP) HFA significantly reduced asthma symptoms in children aged 1 to < 4 years, with a 53.9% reduction in daily symptom scores compared to 44.1% in the placebo group over 12 weeks.

The treatment was well tolerated, with similar rates of adverse events between the FP and placebo groups, and low systemic exposure to the medication, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fluticasone propionate hydrofluoroalkane inhalation aerosol in pre-school-age children with asthma: a randomized, double-blind, placebo-controlled study. Qaqundah, PY., Sugerman, RW., Ceruti, E., et al.[2016]

Inhaled fluticasone propionate at doses of up to 500 microg/day is an effective treatment for mild to moderate asthma, showing significant improvements in lung function and reduced asthma symptoms compared to placebo and other medications.

Fluticasone propionate is well tolerated with a low incidence of adverse effects, and it does not significantly affect the hypothalamo-pituitary-adrenal (HPA) axis, making it a safe option for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled fluticasone propionate: a review of its therapeutic efficacy at dosages Jarvis, B., Faulds, D.[2018]

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EP-104IAR for EoE (RESOLVE Trial)

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These data show that EP-104GI has significant potential as a safe, effective and long-duration treatment for eosinophilic esophagitis (see Figure 1). F1 Figure ...