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

NCT ID: NCT02679508

Last Updated: 2023-12-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 208 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-20
• Study Completion Date: 2022-03-05

Brief Summary

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

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.

Conditions

Erosive Esophagitis

Keywords

Esophagitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vonoprazan group

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

Group Type: EXPERIMENTAL

Vonoprazan

Intervention Type: DRUG

Vonoprazan fumarate 10 mg or 20 mg capsules

Lansoprazole group

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

Group Type: ACTIVE_COMPARATOR

Lansoprazole

Intervention Type: DRUG

Lansoprazole 15 mg or 30 mg capsules

Interventions

Vonoprazan

Vonoprazan fumarate 10 mg or 20 mg capsules

Intervention Type: DRUG

Lansoprazole

Lansoprazole 15 mg or 30 mg capsules

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Tokatsu Tsujinaka Hospital

Abiko, Chiba, Japan

Hohnodai Hospital National Center For Global Health and Medicine

Ichikawa, Chiba, Japan

Red Cross Matsuyama Hospital

Matsuyama, Ehime, Japan

Kawakubo Clinic

Kama, Fukuoka, Japan

Hakodate Hospital

Hakodate, Hokkaido, Japan

Aoyama Medical Clinic

Kobe, Hyōgo, Japan

Hyogo College Of Medicine

Nishinomiya, Hyōgo, Japan

KKR Takamatsu Hospital

Takamatsu, Kagawa-ken, Japan

Shirane Clinic

Sendai, Miyagi, Japan

Tohoku University Hospital

Sendai, Miyagi, Japan

Shin-Beppu Hospital

Beppu, Oita Prefecture, Japan

Kawasaki Medical University

Kurashiki, Okayama-ken, Japan

Shiga Hospital

Ōtsu, Shiga, Japan

Shiga University Of Medical Science Hospital

Ōtsu, Shiga, Japan

Shimane University Hospital

Izumo, Shimane, Japan

Juntendo University Shizuoka Hospital

Izunokuni, Shizuoka, Japan

Kohga Hospital

Yaizu, Shizuoka, Japan

Masuyama Clinic

Ōtawara, Tochigi, Japan

Juntendo University Hospital

Bunkyo-ku, Tokyo, Japan

Banno Clinic

Ōta-ku, Tokyo, Japan

Shimokitazawa Tomo Clinic

Setagaya-ku, Tokyo, Japan

National Center For Global Health and Medicine

Shinjyuku-ku, Tokyo, Japan

Nippon Medical School Hospital

Shinjyuku-ku, Tokyo, Japan

Chihaya Hospital

Fukuoka, , Japan

Harada Hospital

Fukuoka, , Japan

Kimura Shiro Clinic

Fukuoka, , Japan

Kyushu University Hospital

Fukuoka, , Japan

Mori Clinic

Fukuoka, , Japan

Hanabata Clinic

Kumamoto, , Japan

Morinaga Ueno Clinic

Kumamoto, , Japan

Oki Hospital

Kyoto, , Japan

Asahigaoka Hospital

Okayama, , Japan

Kawasaki Hospital

Okayama, , Japan

Arita Hospital

Ōita, , Japan

Matsuki Clinic

Shizuoka, , Japan

Oizumi Medical Clinic

Yamagata, , Japan

Countries

Japan

References

Uemura N, Kinoshita Y, Haruma K, Kushima R, Yao T, Akiyama J, Aoyama N, Baba Y, Suzuki C, Ishiguro K. Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study. Clin Gastroenterol Hepatol. 2025 Apr;23(5):748-757.e5. doi: 10.1016/j.cgh.2024.08.004. Epub 2024 Aug 27.

Reference Type: DERIVED

PMID: 39209187 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b603a4db2bf003ab4a26b

To obtain more information on the study, click here/on this link

Other Identifiers

U1111-1178-8948

Identifier Type: REGISTRY

Identifier Source: secondary_id

JapicCTI-163153

Identifier Type: REGISTRY

Identifier Source: secondary_id

Vonoprazan-4003

Identifier Type: -

Identifier Source: org_study_id