Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Erosive Esophagitis
Condition: Erosive Esophagitis
MeSH terms: Esophagitis
Intervention: Vonoprazan; Lansoprazole
Intervention description: Over-encapsulated tablet administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.; Over-encapsulated capsule administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.
Intervention MeSH terms: Lansoprazole; Dexlansoprazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1027.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Erosive Esophagitis; Vonoprazan; Lansoprazole

Summary:

      To evaluate the efficacy and safety of vonoprazan compared to lansoprazole in participants
      with erosive esophagitis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The participant is ≥18 years of age at the time of informed consent signing.

          2. In the opinion of the investigator or subinvestigators, the participant is capable of
             understanding and complying with protocol requirements.

          3. The participant signs and dates a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedures. The participant
             is informed of the full nature and purpose of the study, including possible risks and
             side-effects. The participant has the ability to cooperate with the investigator.
             Ample time and opportunity should be given to read and understand verbal and/or
             written instructions.

          4. The participant is found to have endoscopically confirmed EE of LA Classification
             Grades A to D during the Screening Period (Visit 1) as assessed by a central
             adjudicator. The target number of participants with LA classification Grade C or D
             will be approximately 30% of the total number of participants (300 total). Enrollment
             of EE participants with Grade A or B will end when the number of participants with
             Grade A or B EE is approximately 700 or 70% of the total planned number of
             participants. Given the invasive nature of an endoscopy, any endoscopic confirmation
             performed in a routine clinical setting before signing the informed consent will be
             acceptable to use for the purpose of fulfilling the screening requirement if all of
             the following apply: (1) appropriate endoscopy pictures were taken; (2) appropriate
             gastric biopsy samples were taken; (3) the endoscopy pictures can be sent to the
             central adjudicator via the adjudication systems; and (4) all screening procedures
             (including the completion of adjudication) AND randomization can be completed within a
             7-day period after the date of the endoscopy.

          5. A female participant of childbearing potential who is or may be sexually active with a
             nonsterilized male partner agrees to routinely use adequate contraception from the
             signing of informed consent until 4 weeks after the last dose of study drug.

        Exclusion Criteria:

          1. The participant's endoscopic examination for entering this study fails to confirm EE
             within 7 days (no later than 10 days on rare occasion with sponsor approval) prior to
             randomization.

          2. The participant is determined to be positive for Helicobacter pylori (HP) or has had
             an HP infection within 45 days of randomization.

          3. The participant has endoscopic Barrett's esophagus (>1 cm of columnar-lined esophagus)
             and/or definite dysplastic changes in the esophagus.

          4. The participant has any other condition affecting the esophagus, including
             eosinophilic esophagitis; esophageal varices; viral or fungal infection; esophageal
             stricture; a history of radiation therapy, radiofrequency ablation, endoscopic mucosal
             resection, or cryotherapy to the esophagus; or any history of caustic or
             physiochemical trauma (including sclerotherapy or esophageal variceal band ligation).
             However, participants diagnosed with Schatzki's ring (mucosal tissue ring around lower
             esophageal sphincter) are eligible to participate.

          5. The participant has scleroderma (systemic sclerosis).

          6. The participant has a history of surgery or endoscopic treatment affecting
             gastroesophageal reflux, including fundoplication and dilation for esophageal
             stricture (except Schatzki's ring) or a history of gastric or duodenal surgery (except
             endoscopic removal of benign polyps).

          7. The participant has an active gastric or duodenal ulcer at the start of the Screening
             Period. Additionally, participants with gastric or duodenal erosions are permitted to
             participate.

          8. The participant has received any investigational compound (including those in post
             marketing studies) within 30 days prior to the start of the Screening Period. A
             participant who has been screen failed from another clinical study and who has not
             been dosed may be considered for enrollment in this study.

          9. The participant is a study site employee, an immediate family member, or is in a
             dependent relationship with a study site employee who is involved in the conduct of
             this study (eg, spouse, parent, child, sibling) or who may have consented under
             duress.

         10. The participant has cutaneous lupus erythematosus or systemic lupus erythematosus.

         11. The participant has had clinically significant upper or lower gastrointestinal
             bleeding within 4 weeks prior to randomization.

         12. The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory
             conditions.

         13. The participant has a history of hypersensitivity or allergies to vonoprazan
             (including the formulation excipients: D-mannitol, microcrystalline cellulose,
             hydroxypropyl cellulose, fumaric acid, croscarmellose sodium, magnesium stearate,
             hypromellose, macrogol 8000, titanium oxide, or red or yellow ferric oxide), PPIs, or
             any excipients used in the 13C-urea breath test: mannitol, citric acid, or aspartame.
             Skin testing may be performed according to local standard practice to confirm
             hypersensitivity.

         14. The participant has a history of alcohol abuse, illegal drug use, or drug addiction
             within the 12 months prior to screening, or regularly consumes >21 units of alcohol (1
             unit = 12 oz/300 mL beer, 1.5 oz/25 mL hard liquor/spirits, or 5 oz/100 mL wine) per
             week based on self-report. Participants must have a negative urine drug screen at
             screening.

         15. The participant is taking any excluded medications or treatments.

         16. If female, the participant is pregnant, lactating, or intending to become pregnant
             before, during, or within 4 weeks after participating in this study; or intending to
             donate ova during such time period.

         17. The participant has a history or clinical manifestations of significant central
             nervous system, cardiovascular, pulmonary, hepatic, renal, metabolic, other
             gastrointestinal, urological, endocrine, or hematological disease that, in the opinion
             of the investigator, would confound the study results or compromise participant
             safety.

         18. The participant requires hospitalization or has surgery scheduled during the course of
             the study or has undergone major surgical procedures within 30 days prior to the
             Screening Visit.

         19. The participant has a history of malignancy (including MALToma) or has been treated
             for malignancy within 5 years prior to the start of the Screening Period (Visit 1).
             (The participant may be included in the study if he/she has cured cutaneous basal cell
             carcinoma or cervical carcinoma in situ).

         20. The participant has acquired immunodeficiency syndrome or human immunodeficiency virus
             infection, or tests positive for the hepatitis B surface antigen, hepatitis C virus
             (HCV) antibody, or HCV RNA. However, participants who test positive for HCV antibody
             but negative for HCV RNA are permitted to participate.

         21. The participant has any of the following abnormal laboratory test values at the start
             of the Screening Period:

               1. Creatinine levels: >2 mg/dL (>177 μmol/L)

               2. Alanine aminotransferase or aspartate aminotransferase >2 × the upper limit of
                  normal (ULN) or total bilirubin >2 × ULN.