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

Primary Purpose

Erosive Esophagitis

Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Vonoprazan
Lansoprazole
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Erosive Esophagitis focused on measuring Esophagitis

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Tokatsu Tsujinaka Hospital
  • Hohnodai Hospital National Center For Global Health and Medicine
  • Red Cross Matsuyama Hospital
  • Kawakubo Clinic
  • Hakodate Hospital
  • Aoyama Medical Clinic
  • Hyogo College Of Medicine
  • KKR Takamatsu Hospital
  • Shirane Clinic
  • Tohoku University Hospital
  • Shin-Beppu Hospital
  • Kawasaki Medical University
  • Shiga Hospital
  • Shiga University Of Medical Science Hospital
  • Shimane University Hospital
  • Juntendo University Shizuoka Hospital
  • Kohga Hospital
  • Masuyama Clinic
  • Juntendo University Hospital
  • Banno Clinic
  • Shimokitazawa Tomo Clinic
  • National Center For Global Health and Medicine
  • Nippon Medical School Hospital
  • Chihaya Hospital
  • Harada Hospital
  • Kimura Shiro Clinic
  • Kyushu University Hospital
  • Mori Clinic
  • Hanabata Clinic
  • Morinaga Ueno Clinic
  • Oki Hospital
  • Arita Hospital
  • Asahigaoka Hospital
  • Kawasaki Hospital
  • Matsuki Clinic
  • Oizumi Medical Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Vonoprazan group

Lansoprazole group

Arm Description

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

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

Outcomes

Primary Outcome Measures

Percentage of participants with clinically significant Gastric mucosa histopathology findings
For each gastric mucosa histopathological endpoint (presence or absence of malignant alteration of epithelial cells, presence or absence of prominence/hyperplasia of wall cells, presence or absence of hyperplasia of crypt epithelial cells, presence or absence of proliferation of endocrine cells, and presence or absence of hyperplasia of G cells), the proportion of research participants who have the events for assessment in maintenance phase shall be calculated for each treatment group.

Secondary Outcome Measures

Endoscopic erosive esophagitis (EE) recurrence rate
EE healing rate at the end of the healing phase
Number of Participants Reporting One or More Treatment-emergent Adverse Events
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.
Percentage of participants with clinically significant endoscopic findings
For each endoscopic endpoint (presence or absence of fundic gland polyp, presence or absence of hyperplastic polyp, presence or absence of cobblestone mucosa, presence or absence of multiple white flat elevation, and presence or absence of black spots), the proportion of research participants who have the clinically significant events at each time point for assessment shall be calculated for each treatment group.
Percentage of participants with clinically significant histological evaluation of gastritis according to the Sydney classification
For each histological endpoint of gastritis according to the Sydney classification [inflammation (mononuclear infiltration), activity (neutrophilic infiltration), atrophy, intestinal metaplasia, and H. pylori], the proportion of research participants who have the clinically significant events at each time point for assessment shall be calculated for each treatment group.
Percentage of participants who have gastric polyp in maintenance phase
For gastric polyp, the proportion of research participants who have gastric polyp in maintenance phase of this study shall be calculated for each treatment group.

Full Information

First Posted
February 8, 2016
Last Updated
April 5, 2022
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT02679508
Brief Title
Vonoprazan Study in Patients With Erosive Esophagitis to Evaluate Long-term Safety
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
March 29, 2016 (Actual)
Primary Completion Date
March 5, 2022 (Actual)
Study Completion Date
March 5, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Erosive Esophagitis
Keywords
Esophagitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
202 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vonoprazan group
Arm Type
Experimental
Arm Description
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
Arm Title
Lansoprazole group
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Vonoprazan
Intervention Description
Vonoprazan fumarate 10 mg or 20 mg capsules
Intervention Type
Drug
Intervention Name(s)
Lansoprazole
Intervention Description
Lansoprazole 15 mg or 30 mg capsules
Primary Outcome Measure Information:
Title
Percentage of participants with clinically significant Gastric mucosa histopathology findings
Description
For each gastric mucosa histopathological endpoint (presence or absence of malignant alteration of epithelial cells, presence or absence of prominence/hyperplasia of wall cells, presence or absence of hyperplasia of crypt epithelial cells, presence or absence of proliferation of endocrine cells, and presence or absence of hyperplasia of G cells), the proportion of research participants who have the events for assessment in maintenance phase shall be calculated for each treatment group.
Time Frame
Up to Week 268
Secondary Outcome Measure Information:
Title
Endoscopic erosive esophagitis (EE) recurrence rate
Time Frame
Up to Week 268
Title
EE healing rate at the end of the healing phase
Time Frame
Up to Week 8
Title
Number of Participants Reporting One or More Treatment-emergent Adverse Events
Description
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.
Time Frame
Up to Week 268
Title
Percentage of participants with clinically significant endoscopic findings
Description
For each endoscopic endpoint (presence or absence of fundic gland polyp, presence or absence of hyperplastic polyp, presence or absence of cobblestone mucosa, presence or absence of multiple white flat elevation, and presence or absence of black spots), the proportion of research participants who have the clinically significant events at each time point for assessment shall be calculated for each treatment group.
Time Frame
Up to Week 268
Title
Percentage of participants with clinically significant histological evaluation of gastritis according to the Sydney classification
Description
For each histological endpoint of gastritis according to the Sydney classification [inflammation (mononuclear infiltration), activity (neutrophilic infiltration), atrophy, intestinal metaplasia, and H. pylori], the proportion of research participants who have the clinically significant events at each time point for assessment shall be calculated for each treatment group.
Time Frame
Up to Week 268
Title
Percentage of participants who have gastric polyp in maintenance phase
Description
For gastric polyp, the proportion of research participants who have gastric polyp in maintenance phase of this study shall be calculated for each treatment group.
Time Frame
Up to Week 268

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Tokatsu Tsujinaka Hospital
City
Abiko
State/Province
Chiba
Country
Japan
Facility Name
Hohnodai Hospital National Center For Global Health and Medicine
City
Ichikawa
State/Province
Chiba
Country
Japan
Facility Name
Red Cross Matsuyama Hospital
City
Matsuyama
State/Province
Ehime
Country
Japan
Facility Name
Kawakubo Clinic
City
Kama
State/Province
Fukuoka
Country
Japan
Facility Name
Hakodate Hospital
City
Hakodate
State/Province
Hokkaido
Country
Japan
Facility Name
Aoyama Medical Clinic
City
Kobe
State/Province
Hyogo
Country
Japan
Facility Name
Hyogo College Of Medicine
City
Nishinomiya
State/Province
Hyogo
Country
Japan
Facility Name
KKR Takamatsu Hospital
City
Takamatsu
State/Province
Kagawa
Country
Japan
Facility Name
Shirane Clinic
City
Sendai
State/Province
Miyagi
Country
Japan
Facility Name
Tohoku University Hospital
City
Sendai
State/Province
Miyagi
Country
Japan
Facility Name
Shin-Beppu Hospital
City
Beppu
State/Province
Oita
Country
Japan
Facility Name
Kawasaki Medical University
City
Kurashiki
State/Province
Okayama
Country
Japan
Facility Name
Shiga Hospital
City
Otsu
State/Province
Shiga
Country
Japan
Facility Name
Shiga University Of Medical Science Hospital
City
Otsu
State/Province
Shiga
Country
Japan
Facility Name
Shimane University Hospital
City
Izumo
State/Province
Shimane
Country
Japan
Facility Name
Juntendo University Shizuoka Hospital
City
Izunokuni
State/Province
Shizuoka
Country
Japan
Facility Name
Kohga Hospital
City
Yaizu
State/Province
Shizuoka
Country
Japan
Facility Name
Masuyama Clinic
City
Otawara
State/Province
Tochigi
Country
Japan
Facility Name
Juntendo University Hospital
City
Bunkyo-ku
State/Province
Tokyo
Country
Japan
Facility Name
Banno Clinic
City
Ota-ku
State/Province
Tokyo
Country
Japan
Facility Name
Shimokitazawa Tomo Clinic
City
Setagaya-ku
State/Province
Tokyo
Country
Japan
Facility Name
National Center For Global Health and Medicine
City
Shinjyuku-ku
State/Province
Tokyo
Country
Japan
Facility Name
Nippon Medical School Hospital
City
Shinjyuku-ku
State/Province
Tokyo
Country
Japan
Facility Name
Chihaya Hospital
City
Fukuoka
Country
Japan
Facility Name
Harada Hospital
City
Fukuoka
Country
Japan
Facility Name
Kimura Shiro Clinic
City
Fukuoka
Country
Japan
Facility Name
Kyushu University Hospital
City
Fukuoka
Country
Japan
Facility Name
Mori Clinic
City
Fukuoka
Country
Japan
Facility Name
Hanabata Clinic
City
Kumamoto
Country
Japan
Facility Name
Morinaga Ueno Clinic
City
Kumamoto
Country
Japan
Facility Name
Oki Hospital
City
Kyoto
Country
Japan
Facility Name
Arita Hospital
City
Oita
Country
Japan
Facility Name
Asahigaoka Hospital
City
Okayama
Country
Japan
Facility Name
Kawasaki Hospital
City
Okayama
Country
Japan
Facility Name
Matsuki Clinic
City
Shizuoka
Country
Japan
Facility Name
Oizumi Medical Clinic
City
Yamagata
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b603a4db2bf003ab4a26b
Description
To obtain more information on the study, click here/on this link

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

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