| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| An inflammation of the cell layer that lines the inside of esophagus. A disease that causes heartburn, a burning sensation in the throat and difficulty and pain when swallowing. |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10063657 |
| E.1.2 | Term | Erosive esophagitis |
| E.1.2 | System Organ Class | 100000004856 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Healing Phase
- To assess the efficacy of vonoprazan (20 mg once daily [QD])
compared to lansoprazole (30 mg QD) in healing of EE over 8 weeks
in subjects with endoscopically proven EE.
- To assess the safety of vonoprazan (20 mg QD) compared to
lansoprazole (30 mg QD) in subjects with endoscopically proven EE.
Maintenance Phase
-To assess the efficacy in maintenance of healing of vonoprazan
(10 mg and 20 mg QD) compared to lansoprazole (15 mg QD) in
subjects with healed EE.
• To assess the safety of vonoprazan (10 mg and 20 mg QD) compared
to lansoprazole (15 mg QD) in subjects with healed EE. |
|
| E.2.2 | Secondary objectives of the trial |
Healing Phase
- To assess the efficacy of vonoprazan (20 mg QD) compared to
lansoprazole (30 mg QD) in healing of EE over 2 weeks in subjects
with endoscopically proven EE.
• To assess the efficacy of vonoprazan (20 mg QD) compared to
lansoprazole (30 mg QD) in healing of EE in subjects with
endoscopically proven EE LA Classification Grades C or D over
2 weeks and 8 weeks.
• To assess relief of heartburn of vonoprazan (20 mg QD) compared to
lansoprazole (30 mg QD) in subjects with endoscopically proven EE
over 8 weeks and within the first 3 days of treatment.
Maintenance Phase
To assess the efficacy in maintenance of healing of vonoprazan
(10 mg and 20 mg QD) compared to lansoprazole (15 mg QD) in
subjects with healed EE with baseline LA Classification Grades C or
D.
• To assess the efficacy of vonoprazan (10 mg and 20 mg QD)
compared to lansoprazole (15 mg QD) in subject symptoms by subject
daily diary. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
-The subject is ≥18 years of age at the time of informed consent signing.
-The subject 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 subjects with LA classification Grade C or D will be approximately 30% of the total number of subjects (300 total). Enrollment of EE subjects with Grade A or B will end when the number of subjects with Grade A or B EE is approximately 700 or 70% of the total planned number of subjects. 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.
-A female subject 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. |
|
| E.4 | Principal exclusion criteria |
-The subject’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
-The subject is determined to be positive for Helicobacter pylori (HP) or has had an HP infection within 45 days of randomization
-The subject has endoscopic Barrett’s esophagus (>1 cm of columnar-lined esophagus)and/or definite dysplastic changes in the esophagus.
-The subject 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, subjects diagnosed with Schatzki’s ring (mucosal tissue ring around lower esophageal sphincter) are eligible to participate.
-The subject has scleroderma (systemic sclerosis).
-The subject 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).
-The subject has an active gastric or duodenal ulcer at the start of the Screening Period. Additionally, subjects with gastric or duodenal erosions are permitted to participate.
-The subject has received any investigational compound (including those in post-marketing studies) within 30 days prior to the start of the Screening Period. A subject who has been screen failed from another clinical study and who has not been dosed may be considered for enrollment in this study.
-The subject 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.
-The subject has cutaneous lupus erythematosus or systemic lupus erythematosus.
-The subject has had clinically significant upper or lower gastrointestinal bleeding within 4 weeks prior to randomization
-The subject has Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.
-The subject 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.
-The subject 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. Subjects must have a negative urine drug screen at screening.
-The subject is taking any excluded medications or treatments listed in the protocol.
-If female, the subject 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.
-The subject 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 subject safety.
-The subject 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.
-The subject 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 subject may be included in the study if he/she has cured cutaneous basal cell carcinoma or cervical carcinoma in situ).
-The subject has acquired immunodeficiency syndrome (AIDS) or human
immunodeficiency virus (HIV) infection, or tests positive for the hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or HCV-RNA. However, subjects who test positive for HCV antibody but negative for HCV-RNA are permitted to participate.
-The subject has any of the following abnormal laboratory test values at the start of the Screening Period:
a) Creatinine levels: >2 mg/dL (>177 μmol/L)
b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upper limit of normal (ULN) or total bilirubin >2 × ULN |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Healing Phase:
The percentage of subjects who have complete healing of EE by Week 8 as assessed by endoscopy
Maintenance Phase:
The percentage of subjects who maintain complete healing of EE after 24 weeks as assessed by endoscopy |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
For Healing Phase Primary Endpoint - up to 8 weeks of treatment.
For Maintenance Phase Primary Endpoint - after 24 weeks. |
|
| E.5.2 | Secondary end point(s) |
Healing Phase:
• The percentage of subjects who have complete healing of EE at Week 2 as assessed by endoscopy
• The percentage of subjects who have complete healing of EE at Week 2 as assessed by endoscopy for subjects with baseline LA Classification Grades C or D
• The percentage of subjects who have complete healing of EE by Week 8 as assessed by endoscopy for subjects with baseline LA Classification Grades C or D
• The percentage of 24-hour heartburn–free days over the Healing Phase as assessed by the daily diary
• The percentage of subjects with onset of sustained resolution of heartburn by Day 3(sustained resolution is defined as at least 7 consecutive days with no daytime or nighttime heartburn as assessed by the daily diary)
Maintenance Phase:
• The percentage of subjects who maintain complete healing of EE after 24 weeks as
assessed by endoscopy for subjects with baseline LA Classification Grades C or D
• The percentage of 24-hour heartburn–free days over the Maintenance Phase as assessed
by the daily diary |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Healing Phase - after week 2, 8.
Maintenance Phase - after week 24. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 52 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Czech Republic |
| Hungary |
| Poland |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study is defined in the Protocol as the date on which the last subject completes the last visit (includes follow-up visit which is at 4 weeks after last study drug administration). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 16 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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