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

Erosive Esophagitis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02679508
• Other study ID #: Vonoprazan-4003
• Secondary ID: U1111-1178-8948J
• Status: Completed
• Phase: Phase 4
• Start date: March 20, 2016
• Est. completion date: March 5, 2022

Study information

• Verified date: December 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: March 5, 2022
• Est. primary completion date: March 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Erosive Esophagitis
• Esophagitis

Intervention

Drug:
• Vonoprazan
Vonoprazan fumarate 10 mg or 20 mg capsules
• Lansoprazole
Lansoprazole 15 mg or 30 mg capsules

Locations

Country	Name	City	State
Japan	Tokatsu Tsujinaka Hospital	Abiko	Chiba
Japan	Shin-Beppu Hospital	Beppu	Oita
Japan	Juntendo University Hospital	Bunkyo-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	Hakodate Hospital	Hakodate	Hokkaido
Japan	Hohnodai Hospital National Center For Global Health and Medicine	Ichikawa	Chiba
Japan	Shimane University Hospital	Izumo	Shimane
Japan	Juntendo University Shizuoka Hospital	Izunokuni	Shizuoka
Japan	Kawakubo Clinic	Kama	Fukuoka
Japan	Aoyama Medical Clinic	Kobe	Hyogo
Japan	Hanabata Clinic	Kumamoto
Japan	Morinaga Ueno Clinic	Kumamoto
Japan	Kawasaki Medical University	Kurashiki	Okayama
Japan	Oki Hospital	Kyoto
Japan	Red Cross Matsuyama Hospital	Matsuyama	Ehime
Japan	Hyogo College Of Medicine	Nishinomiya	Hyogo
Japan	Arita Hospital	Oita
Japan	Asahigaoka Hospital	Okayama
Japan	Kawasaki Hospital	Okayama
Japan	Banno Clinic	Ota-ku	Tokyo
Japan	Masuyama Clinic	Otawara	Tochigi
Japan	Shiga Hospital	Otsu	Shiga
Japan	Shiga University Of Medical Science Hospital	Otsu	Shiga
Japan	Shirane Clinic	Sendai	Miyagi
Japan	Tohoku University Hospital	Sendai	Miyagi
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	Matsuki Clinic	Shizuoka
Japan	KKR Takamatsu Hospital	Takamatsu	Kagawa
Japan	Kohga Hospital	Yaizu	Shizuoka
Japan	Oizumi Medical Clinic	Yamagata

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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