Vonoprazan Study in Patients With Erosive Esophagitis to Evaluate Long-term Safety

Study Overview
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Brief Summary
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The purpose of this study is exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration (260 weeks: 5 years) of vonoprazan 10 mg or 20 mg in patients receiving maintenance treatment after healed erosive esophagitis (EE), and the curative effect of vonoprazan 20 mg versus lansoprazole in patients with EE.

Detailed Description
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This is a multicenter, open-label, randomized, parallel-group study to exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration of vonoprazan in maintenance treatment after healed EE, and the curative effect of vonoprazan versus lansoprazole in participants with EE. Participants endoscopically diagnosed with EE of Los Angeles (LA) Classification Grades A to D at the start of treatment (Week 0 of the healing phase) will be randomly assigned to receive either vonoprazan 20 mg or lansoprazole 30 mg to be taken once daily for up to 8 weeks. Subjects with healed EE as confirmed endoscopically at Week 4 or 8 in the healing phase will enter the maintenance phase. In the maintenance phase, the vonoprazan group and the lansoprazole group will be administered a starting dose of 10 mg and 15 mg, respectively, once daily up to 260 weeks. If the principal investigator or investigator judged the effect of vonoprazan 10 mg or lansoprazole 15 mg to be insufficient as the maintenance treatment of EE, vonoprazan and lansoprazole may be increased to 20 mg and 30 mg, respectively. The research period will consist of two subperiods: healing phase in which participants with EE will receive treatment (for 4 or 8 weeks) and maintenance phase in which participants will receive maintenance treatment (for 260 weeks), and thus, a total of up to 268 weeks. The number of visits will be a maximum of 18 visits. Planned number of research subjects, as the number of research subjects for entry to the maintenance phase, will be 130 participants in the vonoprazan group and 65 participants in the lansoprazole group.

Official Title
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Vonoprazan Study In Patients With Erosive Esophagitis to Evaluate Long-term Safety: A Study to Evaluate the Safety of Long-term Administration of Vonoprazan in Maintenance Treatment in Patients With Erosive Esophagitis (EE)

Conditions
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Erosive Esophagitis

Intervention / Treatment
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* Drug: Vonoprazan
* Drug: Lansoprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Healing Phase: Participants endoscopically diagnosed with EE of grades A to D by the LA Classification Grading System at the start of treatment (Week 0 of the healing phase) Participants with H. pylori negative Participants who, in the opinion of the principal investigator or investigator, are capable of understanding the content of the clinical research and complying with the research protocol requirements. Participants who can sign and date an informed consent form and information sheet prior to the conduction of the clinical research procedures. Male or female participants aged 20 years or older at the time of informed consent Therapeutic category: Ambulatory Maintenance Phase: Participants who have endoscopically confirmed EE healing* (mucous membrane disorder is not observed) at completion of the healing phase (Week 4 or 8 of the healing phase) * Participants who are classified as grade 0 according to severity classification of EE (See Table 9.b) Participants who have been determined to be appropriate as subjects for maintenance treatment of EE by the principal investigator or investigator Exclusion Criteria: Healing Phase: Participants with concurrent peptic ulcer (except scarred stage) or Zollinger-Ellison syndrome Participants who received treatment with PPIs (including vonoprazan) within 4 weeks (Week -4 to Week 0) prior to the start of healing phase (Week 0 of the healing phase) Participants with a history of H. pylori eradication. Participants who have received surgery or treatment affecting gastroesophageal reflux (fundoplication or dilation for esophageal stenosis [excluding Schatzki's ring], etc.) Participants with an esophagus-related complication (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal stenosis, etc.), a history of radiotherapy or cryotherapy of the esophagus, a caustic or physiochemical trauma (esophageal sclerotherapy, etc.). However, participants with Schatzki's ring (mucosal tissue ring around inferior esophageal sphincter) or Barrett's esophagus are allowed to be included. Participants with clinically apparent hepatic impairment (e.g., AST or ALT levels at the time of informed consent: >1.5 times the upper limit of normal (ULN). Participants with renal impairment or renal failure [creatinine clearance (CCr) ˂30 mL/min, etc.] Participants with a history of hypersensitivity or allergy for PPIs. Participants with a history of gastrectomy, gastrointestinal resection, or vagotomy Participants with a malignant tumor Participants who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant Participants with one of the diseases listed under administration contraindication in the vonoprazan or lansoprazole package insert Participants planning to take prohibited concomitant medications during the research period Participants participating in other clinical studies Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator Maintenance Phase: Participants who have taken PPIs other than the study drug or the control drug during the healing phase Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vonoprazan group<br>Vonoprazan 20 mg administered orally once daily in the healing phase + vonoprazan 10 mg (as the initial dose and adjusted to vonoprazan 10 mg or 20 mg) administered orally once daily in the maintenance phase | Drug: Vonoprazan<br>* Vonoprazan fumarate 10 mg or 20 mg capsules<br>|
| Active Comparator: Lansoprazole group<br>Lansoprazole 30 mg administered orally once daily in the healing phase + lansoprazole 15 mg (as the initial dose and adjusted to lansoprazole 15 mg or 30 mg) administered orally once daily in the maintenance phase | Drug: Lansoprazole<br>* Lansoprazole 15 mg or 30 mg capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Malignant Alteration of Epithelial Cells | Numbers of participants with malignant alteration of epithelial cells for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis. | Time Frame: Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Parietal Cell Protrusion/Hyperplasia | Numbers of participants with parietal cell protrusion/hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Foveolar Hyperplasia | Numbers of participants with foveolar hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Enterochromaffin-like-cell Hyperplasia | Numbers of participants with enterochromaffin-like-cell hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With G-cell Hyperplasia | Numbers of participants with G-cell hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Recurrence of Erosive Esophagitis (EE) | Erosive esophagitis recurrence is defined as endoscopically confirmed to have erosive esophagitis (LA classification grades O and A to D) during the Maintenance Phase. The LA classification graded as follows- Grade O: normal mucosa; Grade A: nonconfluent mucosal breaks <5 mm in length; Grade B: nonconfluent mucosal breaks ≥ 5mm in length; Grade C: confluent mucosal breaks <75% circumferential; Grade D: confluent mucosal breaks >75% circumferential. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Percentage of Participants Who Healed EE at the End of Healing Phase | Percentage of participants who healed EE at the end of healing phase was reported. | Up to Week 8 | 
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) in Maintenance Phase | Number of participants reporting one or more TEAEs in Maintenance Phase was reported. An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. | 260 weeks (Baseline, up to the end of Maintenance Phase) | 
| Number of Participants With Fundic Gland Polyp | Numbers of participants with fundic gland polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Hyperplastic Polyp | Numbers of participants with hyperplastic polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Cobblestone Mucosa | Numbers of participants with cobblestone mucosa for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Multiple White and Flat Elevated Lesions | Numbers of participants with multiple white and flat elevated lesions for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Black Spots | Numbers of participants with black spots for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Middle Gastric Body | Numbers of participants with inflammation (mononuclear infiltration) in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Antrum | Numbers of participants with inflammation (mononuclear infiltration) in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Neutrophilic Infiltration in Greater Curvature of Middle Gastric Body | Numbers of participants with neutrophilic infiltration in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Neutrophilic Infiltration in Greater Curvature of Antrum | Numbers of participants with neutrophilic infiltration in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Atrophy in Greater Curvature of Middle Gastric Body | Numbers of participants with atrophy in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Atrophy in Greater Curvature of Antrum | Numbers of participants with atrophy in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Intestinal Metaplasia in Greater Curvature of Middle Gastric Body | Numbers of participants with intestinal metaplasia in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Intestinal Metaplasia in Greater Curvature of Antrum | Numbers of participants with intestinal metaplasia in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Presence of H.Pylori in Greater Curvature of Middle Gastric Body | Numbers of participants with presence of H.pylori in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Presence of H.Pylori in Greater Curvature of Antrum | Numbers of participants with presence of H.pylori in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis. | Up to Week 268 (Week 260 in Maintenance Phase) | 
| Number of Participants With Gastric Polyp | Numbers of participants with gastric polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported. The number analyzed is the number of participants with data available for analysis. | Up to Week 268 (Week 260 in Maintenance Phase) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophagitis