Vonoprazan study in patients with erosive esophagitis to evaluate long-term safety (VISION Study)

JRCT ID: jRCT1080223099

Registered date:08/02/2016

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: Erosive esophagitis
• Date of first enrollment: 20/03/2016
• Target sample size: 202
• Countries of recruitment: Japan
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : Vonoprazan
INN of investigational material : Vonoprazan
Therapeutic category code : 232 Agents for peptic ulcer
Dosage and Administration for Investigational material : 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

control material(s)
Generic name etc : Lansoprazole
INN of investigational material : Lansoprazole
Therapeutic category code : 232 Agents for peptic ulcer
Dosage and Administration for Investigational material : 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

Outcome(s)

Primary Outcome

1.Number of Participants with Malignant Alteration of Epithelial Cells
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

2.Number of Participants with Parietal Cell Protrusion/Hyperplasia
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

3.Number of Participants with Foveolar Hyperplasia
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

4.Number of Participants with Enterochromaffin-like-cell Hyperplasia
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

5.Number of Participants with G-cell Hyperplasia
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

Secondary Outcome

1.Percentage of Participants with Recurrence of Erosive Esophagitis (EE)
Time Frame: Up to Week 268 (Week 260 in Maintenance Phase)
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.

2.Percentage of Participants who Healed EE at the End of the Healing Phase
Time Frame: Up to Week 8
Percentage of participants who healed EE at the end of healing phase was reported.

3.Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) in Maintenance Phase
Time Frame: 260 weeks (Baseline, up to the end of 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 treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

4.Number of Participants with Fundic Gland Polyp
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

5.Number of Participants with Hyperplastic Polyp
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

6.Number of Participants with Cobblestone Mucosa
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

7.Number of Participants with Multiple White and Flat Elevated Lesions
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

8.Number of Participants with Black Spots
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

9.Number of Participants with Inflammation (Mononuclear Infiltration) in Greater Curvature of Middle Gastric Body
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

10.Number of Participants with Inflammation (Mononuclear Infiltration) in Greater Curvature of Antrum
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

11.Number of Participants with Neutrophilic Infiltration in Greater Curvature of Middle Gastric Body
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
Numbers of participants with neutrophilic infiltration in greater curvature of middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

12.Number of Participants with Neutrophilic Infiltration in Greater Curvature of Antrum
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
Numbers of participants with neutrophilic infiltration in greater curvature of antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

13.Number of Participants with Atrophy in Greater Curvature of Middle Gastric Body
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
Numbers of participants with atrophy in greater curvature of middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

14.Number of Participants with Atrophy in Greater Curvature of Antrum
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
Numbers of participants with atrophy in greater curvature of antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

15.Number of Participants with Intestinal Metaplasia in Greater Curvature of Middle Gastric Body
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
Numbers of participants with intestinal metaplasia in greater curvature of middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

16.Number of Participants with Intestinal Metaplasia in Greater Curvature of Antrum
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
Numbers of participants with intestinal metaplasia in greater curvature of antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

17.Number of Participants with Presence of H.pylori in Greater Curvature of Middle Gastric Body
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
Numbers of participants with presence of H.pylori in greater curvature of middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

18.Number of Participants with Presence of H.pylori in Greater Curvature of Antrum
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
Numbers of participants with presence of H.pylori in greater curvature of antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

19.Number of Participants with Gastric Polyp
Timeframe: Up to Week 268 (Week 260 in Maintenance Phase)
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.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

< At the start of 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

< At the start of 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
8.Participants who have been determined to be appropriate as subjects for maintenance treatment of EE by the principal investigator or investigator

Exclude criteria

< At the start of 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

<At the start of 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 Information

• Primary Sponsor: Akiyama Junichi
• Secondary Sponsor: Takeda Pharmaceutical Company Limited
• Source(s) of Monetary Support: Takeda Pharmaceutical Company Limited
• Secondary ID(s): NCT02679508,JapicCTI-163153