Clinical trial NCT02679508: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Erosive Esophagitis
Keywords: Esophagitis
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-02-10
Enrollment: 208
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Malignant Alteration of Epithelial Cells
timeFrame: Time Frame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Parietal Cell Protrusion/Hyperplasia
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Foveolar Hyperplasia
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Enterochromaffin-like-cell Hyperplasia
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With G-cell Hyperplasia
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
Secondary outcomes:
measure: Percentage of Participants With Recurrence of Erosive Esophagitis (EE)
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Percentage of Participants Who Healed EE at the End of Healing Phase
timeFrame: Up to Week 8
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) in Maintenance Phase
timeFrame: 260 weeks (Baseline, up to the end of Maintenance Phase)
measure: Number of Participants With Fundic Gland Polyp
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Hyperplastic Polyp
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Cobblestone Mucosa
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Multiple White and Flat Elevated Lesions
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Black Spots
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Middle Gastric Body
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Antrum
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Neutrophilic Infiltration in Greater Curvature of Middle Gastric Body
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Neutrophilic Infiltration in Greater Curvature of Antrum
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Atrophy in Greater Curvature of Middle Gastric Body
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Atrophy in Greater Curvature of Antrum
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Intestinal Metaplasia in Greater Curvature of Middle Gastric Body
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Intestinal Metaplasia in Greater Curvature of Antrum
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: 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)
measure: Number of Participants With Presence of H.Pylori in Greater Curvature of Antrum
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
measure: Number of Participants With Gastric Polyp
timeFrame: Up to Week 268 (Week 260 in Maintenance Phase)
Other outcomes:
Locations:
city: Abiko
country: Japan
facility: Tokatsu Tsujinaka Hospital
state: Chiba
city: Ichikawa
country: Japan
facility: Hohnodai Hospital National Center For Global Health and Medicine
state: Chiba
city: Matsuyama
country: Japan
facility: Red Cross Matsuyama Hospital
state: Ehime
city: Kama
country: Japan
facility: Kawakubo Clinic
state: Fukuoka
city: Hakodate
country: Japan
facility: Hakodate Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Aoyama Medical Clinic
state: Hyogo
city: Nishinomiya
country: Japan
facility: Hyogo College Of Medicine
state: Hyogo
city: Takamatsu
country: Japan
facility: KKR Takamatsu Hospital
state: Kagawa
city: Sendai
country: Japan
facility: Shirane Clinic
state: Miyagi
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Beppu
country: Japan
facility: Shin-Beppu Hospital
state: Oita
city: Kurashiki
country: Japan
facility: Kawasaki Medical University
state: Okayama
city: Otsu
country: Japan
facility: Shiga Hospital
state: Shiga
city: Otsu
country: Japan
facility: Shiga University Of Medical Science Hospital
state: Shiga
city: Izumo
country: Japan
facility: Shimane University Hospital
state: Shimane
city: Izunokuni
country: Japan
facility: Juntendo University Shizuoka Hospital
state: Shizuoka
city: Yaizu
country: Japan
facility: Kohga Hospital
state: Shizuoka
city: Otawara
country: Japan
facility: Masuyama Clinic
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Ota-ku
country: Japan
facility: Banno Clinic
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Shimokitazawa Tomo Clinic
state: Tokyo
city: Shinjyuku-ku
country: Japan
facility: National Center For Global Health and Medicine
state: Tokyo
city: Shinjyuku-ku
country: Japan
facility: Nippon Medical School Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Chihaya Hospital
city: Fukuoka
country: Japan
facility: Harada Hospital
city: Fukuoka
country: Japan
facility: Kimura Shiro Clinic
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukuoka
country: Japan
facility: Mori Clinic
city: Kumamoto
country: Japan
facility: Hanabata Clinic
city: Kumamoto
country: Japan
facility: Morinaga Ueno Clinic
city: Kyoto
country: Japan
facility: Oki Hospital
city: Oita
country: Japan
facility: Arita Hospital
city: Okayama
country: Japan
facility: Asahigaoka Hospital
city: Okayama
country: Japan
facility: Kawasaki Hospital
city: Shizuoka
country: Japan
facility: Matsuki Clinic
city: Yamagata
country: Japan
facility: Oizumi Medical Clinic
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: