A Study to Evaluate the Efficacy and Safety of Vonoprazan 10 mg Compared to Placebo for Relief of Episodic Heartburn in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease Through 24 Weeks

Official title

A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Vonoprazan 10 mg Compared to Placebo for Relief of Episodic Heartburn in Subjects With Symptomatic Non-Erosive Gastroesophageal Reflux Disease Through 24 Weeks

Overview

The main objective is to assess the efficacy of vonoprazan (10 mg as needed) compared to placebo (as needed) in relief of episodic heartburn at 2 hours that is sustained for 24 hours over 12 weeks of treatment in participants with non-erosive gastroesophageal reflux disease (GERD).

Interventions

• Drug Vonoprazan
  Oral tablet.
• Drug Placebo
  Oral tablet.

Primary outcome measures

• Percentage of Treated Heartburn Episodes Achieving Complete Relief at 2 Hours and Sustained Relief for 24 Hours up to Week 12 [Time frame: Up to Week 12]

Secondary outcome measures (7)

• Percentage of Treated Heartburn Episodes Improved at 2 Hours With Sustained Relief for 24 Hours up to Week 12 [Time frame: Up to Week 12]
• Percentage of Treated Heartburn Episodes Improved at 1 Hour With Sustained Relief for 24 Hours up to Week 12 [Time frame: Up to Week 12]
• Percentage of Treated Heartburn Episodes Improved at 2 Hours up to Week 12 [Time frame: Up to Week 12]
• Percentage of Treated Heartburn Episodes Improved at 1 Hour up to Week 12 [Time frame: Up to Week 12]
• Percentage of Treated Heartburn Episodes Achieving Complete Relief at 2 Hours and Sustained Relief for 24 hours up to Week 24 [Time frame: Up to Week 24]
• Percentage of Treated Heartburn Episodes Improved at 30 Minutes With Sustained Relief for 24 Hours up to Week 12 [Time frame: Up to Week 12]
• Percentage of Treated Heartburn Episodes Improved at 30 Minutes up to Week 12 [Time frame: Up to Week 12]

Eligibility criteria

Inclusion Criteria for Run-in Period:

• The participant is ≥18 years of age at the time of informed consent signing.
• In the opinion of the Investigator or Sub-investigators, the participant is capable of understanding and complying with protocol requirements, including compliance with the electronic diary.
• The participant signs and dates a written informed consent form (ICF) 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.
• The participant has a diagnosis of non-erosive GERD with heartburn as the participant's predominant symptom prior to the Screening Period as documented in the medical history and/or as assessed and documented by the Investigator (ie, medical records or other study related documents).
• History of onset of heartburn at least 6 months prior to the Screening Period.
• Heartburn reported on average 4 or more days per week and 4 or more days during the last 7 days of the Screening Period as recorded in the electronic diary.
• 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 as detailed in the protocol.

Inclusion Criteria for Placebo-controlled Timed-assessment Period:

• The participant completes the Run-In Period, during which the participant was at least 80% compliant with open-label study drug.
• The participant has stable disease, ie, no heartburn on the last 7 days of the Run-In Period.
• The participant continues to fulfill all eligibility criteria for the Run-In Period except heartburn reported on average 4 or more days per week and 4 or more days during the last 7 days of the Screening Period as recorded in the electronic diary.
• Participant completes at least 80% of diary entries during the Run-In Period and completes at least 6 of 7 (86%) diary entries over the last 7 days of the Run-In Period.

Exclusion Criteria for Run-in Period:

• The participant has endoscopically confirmed erosive esophagitis (EE) during the Screening Period or was diagnosed with EE within 2 weeks prior to the Screening Period.
• The participant has uncontrolled irritable bowel syndrome (IBS) or has had a flare of IBS requiring therapy within the prior 6 months.
• The participant has a history of or is suspected of having:

• Functional heartburn, as described in the Rome V criteria.
• Functional dyspepsia, as described in the Rome V criteria.
• The participant has endoscopic Barrett's esophagus (>1 cm of columnar-lined esophagus) and/or definite dysplastic changes in the esophagus.
• The participant tests positive for H. pylori infection during the Screening Period, after ≥ 4 weeks free from antibiotics and bismuth and ≥ 2 weeks free from proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), and histamine-2 receptor antagonists (H2RAs).
• The participant has any other clinically significant 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) or hiatal hernia are eligible to participate.
• 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).
• The participant has had gastric or duodenal ulcer(s) within 4 weeks before the first dose of study drug.
• The participant requires or is expected to require use of prescription or non-prescription PPIs, PCABs, or H2RAs throughout the study.
• The participant has received any investigational compound (including those in post-marketing studies) within 30 days prior to the start of the Screening Period or has ever received vonoprazan in a clinical trial (including participation in Study NERD-201 \[NCT04799158\] or NERD-301 \[NCT05195528\]). 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.
• 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.
• The participant has had clinically significant upper or lower gastrointestinal bleeding within 4 weeks prior to the Screening Period.
• The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.
• 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, ascorbic acid, magnesium stearate, hypromellose, macrogol 8000, titanium oxide, or red ferric oxide). Skin testing may be performed according to local standard practice to confirm hypersensitivity.
• The participant has a history of alcohol abuse, illegal drug use, drug addiction, 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 within the 12 months prior to screening. Participants must have a negative urine drug screen for non-prescribed medications at screening. Participants taking prescription drugs will be allowed. Occasional, recreational use of cannabis is allowed. However, participants with a cannabis use disorder (eg, frequent use, functional-social impairment, withdrawal symptoms) per the opinion of the Investigator should be excluded.
• The participant is taking any excluded medications or treatments listed in the protocol.
• 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.
• The participant has a history or clinical manifestations of significant central nervous system, cardiovascular, pulmonary, metabolic, other gastrointestinal, urological, endocrine, or hematological disease that, in the opinion of the Investigator, would confound the study results or compromise participant safety.
• 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 Period.
• The participant has a history of malignancy (including mucosa-associated lymphoid tissue lymphoma) 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 recovered from cutaneous basal cell carcinoma or cervical carcinoma in situ).
• The participant has acquired immunodeficiency syndrome or human immunodeficiency virus (HIV) infection, or tests positive for the hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or HCV-ribonucleic acid (RNA). However, participants who test positive for HCV antibody but negative for HCV-RNA are permitted to participate.
• The participant has moderate to severe hepatic impairment \[Child-Pugh Class B and Child-Pugh Class C\].
• The participant has severe renal impairment \[estimated glomerular filtration rate <30 mL/min\]).
• The participant has any of the following abnormal laboratory test values at the start of the Screening Period:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upper limit of normal (ULN) or total bilirubin >2 × ULN (except participants with Gilbert Syndrome).
• Creatinine levels: >2 mg/dL (>177 μmol/L).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07752407 · NERD-302

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗