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

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)

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.

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.

Inclusion Criteria

Healing Phase:

1. 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)

2. Participants with H. pylori negative

3. 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.

4. Participants who can sign and date an informed consent form and information sheet prior to the conduction of the clinical research procedures.

5. Male or female participants aged 20 years or older at the time of informed consent

6. Therapeutic category: Ambulatory

   Maintenance Phase:

7. 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)

8. 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:

1. Participants with concurrent peptic ulcer (except scarred stage) or Zollinger-Ellison syndrome

2. 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)

3. Participants with a history of H. pylori eradication.

4. Participants who have received surgery or treatment affecting gastroesophageal reflux (fundoplication or dilation for esophageal stenosis [excluding Schatzki's ring], etc.)

5. 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.

6. 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).

7. Participants with renal impairment or renal failure [creatinine clearance (CCr) ˂30 mL/min, etc.]

8. Participants with a history of hypersensitivity or allergy for PPIs.

9. Participants with a history of gastrectomy, gastrointestinal resection, or vagotomy

10. Participants with a malignant tumor

11. Participants who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant

12. Participants with one of the diseases listed under administration contraindication in the vonoprazan or lansoprazole package insert

13. Participants planning to take prohibited concomitant medications during the research period

14. Participants participating in other clinical studies

15. Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator

    Maintenance Phase:

16. Participants who have taken PPIs other than the study drug or the control drug during the healing phase

17. Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator