Clinical trial NCT05195528: A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo for Relief of Heartburn in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (NERD)
Official title: A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Vonoprazan 10 and 20 mg Compared to Placebo for Relief of Heartburn in Subjects With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (NERD) After 4 Weeks and to Evaluate the Efficacy and Safety of Vonoprazan 10 and 20 mg for Relief of Heartburn in Subjects With NERD After 6 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Erosive Gastro-Esophageal Reflux Disease
Heartburn
Keywords: NERD
Vonoprazan
Lead sponsor: Phathom Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-19
Enrollment: 776
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to assess the efficacy of vonoprazan (10 mg and 20 mg once daily \[QD\]) compared to placebo (QD) in relief of heartburn over 4 weeks in participants with NERD.


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, including compliance with the electronic diary.
3. 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.
4. The subject has a diagnosis of symptomatic gastroesophageal reflux disease (GERD) with heartburn as the subject's predominant symptom prior to the Screening Period, as documented in the subject's medical record.
5. History of onset of heartburn at least 6 months prior to the Screening Period.
6. Heartburn reported on 4 or more days during any consecutive 7-day period of the Screening Period as recorded in the electronic diary.
7. A female participant of childbearing potential who is or may be sexually active with a non-sterilized 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 has endoscopically confirmed erosive esophagitis (EE) during the Screening Period. Endoscopy conducted during the Screening Period should be performed after participants meet Inclusion Criterion 6 (i.e., heartburn reported on 4 or more days during any consecutive 7-day period of the Screening Period as recorded in the electronic diary).
2. The participant has active irritable bowel syndrome (IBS) or has had a flare of IBS requiring therapy within the prior 6 months.
3. The participant has a history of or is suspected of having functional upper gastrointestinal disorders, such as:

   1. Functional heartburn, as described in the Rome IV Criteria.
   2. Functional dyspepsia, as described in the Rome IV Criteria.
4. The participant has endoscopic Barrett's esophagus (\>1 cm of columnar-lined esophagus) and/or definite dysplastic changes in the esophagus.
5. 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.
6. The participant has scleroderma (systemic sclerosis) or systemic lupus erythematosus.
7. The participant has a history of surgery or endoscopic treatment affecting gastroesophageal reflux, including fundoplication and dilation for esophageal stricture (except dilation for a Schatzki's ring) or a history of gastric or duodenal surgery (except endoscopic removal of benign polyps).
8. The participant has an active gastric or duodenal ulcer within 4 weeks before the first dose of study drug.
9. The participant requires or is expected to require use of prescription or non-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) throughout the study.
10. 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 vonoprazan in a clinical trial at any time (including participation in Study NERD-201). 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.
11. 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.
12. The participant has had clinically significant upper or lower gastrointestinal bleeding within 4 weeks prior to the Screening Period.
13. The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.
14. 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, and titanium oxide, or red or yellow ferric oxide). Skin testing may be performed according to local standard practice to confirm hypersensitivity.
15. 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 for cannabinoids/tetrahydrocannabinol (including prescription cannabinoids) and non-prescribed medications during the Screening Period.
16. The participant is taking any excluded medications or treatments listed in the protocol, including prescription cannabinoids/tetrahydrocannabinol.
17. 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.
18. 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.
19. The participant requires hospitalization or has surgery scheduled during the course of the study (from Visit 1 to end of Follow-up Period at Visit 10) or has undergone major surgical procedures within 30 days prior to the Screening Period.
20. 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 cured cutaneous basal cell carcinoma or cervical carcinoma in situ).
21. 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-ribonucleic acid (RNA). However, participants who test positive for HCV antibody but negative for HCV-RNA are permitted to participate.
22. 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 (ALT) or aspartate aminotransferase (AST) \>2 × the upper limit of normal (ULN) or total bilirubin \>2 × ULN (except for participants with a diagnosis of Gilbert's syndrome).
23. The subject tests positive for active H pylori infection during the Screening Period, after ≥4 weeks free from antibiotics and bismuth and ≥2 weeks free from PPIs and histamine-2 receptor antagonists (H2RAs).

Primary outcomes:
measure: Percentage of Days Without Daytime or Nighttime Heartburn
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: Percentage of Days Without Rescue Antacid Use
timeFrame: Day 1 to Day 28
Other outcomes:
Locations:
city: Athens
country: United States
facility: North Alabama Research Center LLC
state: Alabama
city: Cullman
country: United States
facility: Cullman Research Center
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center Inc
state: Alabama
city: Mobile
country: United States
facility: East View Medical Research, LLC
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies - Phoenix - Clinedge
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management - Clinedge
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners - ClinEdge
state: Arkansas
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Canoga Park
country: United States
facility: Alliance Research Institute
state: California
city: Chula Vista
country: United States
facility: GW Research, Inc
state: California
city: Chula Vista
country: United States
facility: eStudy Site
state: California
city: Corona
country: United States
facility: Kindred Medical Institute for Clinical Trials, LLC
state: California
city: Encinitas
country: United States
facility: BG Clinical Research
state: California
city: Garden Grove
country: United States
facility: Paragon Rx Clinical
state: California
city: Lancaster
country: United States
facility: OM Research LLC
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute
state: California
city: Rancho Cucamonga
country: United States
facility: Prospective Research Innovations
state: California
city: Sacramento
country: United States
facility: Northern California Research Corp
state: California
city: San Carlos
country: United States
facility: Digestive Care Center
state: California
city: San Diego
country: United States
facility: Clinical Applications Laboratories Inc
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group, Inc.
state: California
city: Santa Ana
country: United States
facility: Paragon Rx Clinical, Inc.
state: California
city: Wheat Ridge
country: United States
facility: Western States Clinical Research Inc
state: Colorado
city: Bridgeport
country: United States
facility: Gastroenterology Associates of Fairfield County
state: Connecticut
city: Bristol
country: United States
facility: Connecticut Clinical Research Institute
state: Connecticut
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: Edgewater
country: United States
facility: Velocity Clinical Research - New Smyrna Beach
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: ENCORE Borland-Groover Clinical Research
state: Florida
city: Maitland
country: United States
facility: ClinCloud
state: Florida
city: Ocoee
country: United States
facility: Legacy Clinical Solutions: Sensible HealthCare, LLC
state: Florida
city: Orange Park
country: United States
facility: Digestive Disease Consultants, PA
state: Florida
city: Orlando
country: United States
facility: Medical Center
state: Florida
city: Palm Harbor
country: United States
facility: Advanced Gastroenterology Associates, LLC
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research
state: Florida
city: Tampa
country: United States
facility: Guardian Angel Research
state: Florida
city: Dalton
country: United States
facility: Southeast Clinical Research Center
state: Georgia
city: Decatur
country: United States
facility: Atlanta Center For Gastroenterology PC
state: Georgia
city: Macon
country: United States
facility: Gastroenterology Associates of Central Georgia, LLC
state: Georgia
city: Roswell
country: United States
facility: Atlanta Center For Clinical Research
state: Georgia
city: Sandy Springs
country: United States
facility: Mount Vernon Clinical Research, LLC
state: Georgia
city: Suwanee
country: United States
facility: In Quest Medical Research
state: Georgia
city: Boise
country: United States
facility: Treasure Valley Medical Research
state: Idaho
city: Idaho Falls
country: United States
facility: Grand Teton Research Group, PLLC
state: Idaho
city: Clive
country: United States
facility: Iowa Digestive Disease Center
state: Iowa
city: Topeka
country: United States
facility: Kansas Medical Clinic
state: Kansas
city: Covington
country: United States
facility: Clinical Trials Management LLC
state: Louisiana
city: Lafayette
country: United States
facility: Combined Gastro Research
state: Louisiana
city: Marrero
country: United States
facility: Tandem Clinical Research, LLC
state: Louisiana
city: West Monroe
country: United States
facility: Clinical Trials of America, LLC
state: Louisiana
city: Annapolis
country: United States
facility: Investigative Clinical Research
state: Maryland
city: Chelmsford
country: United States
facility: Digestive Health Specialists
state: Massachusetts
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, PLC
state: Michigan
city: Minneapolis
country: United States
facility: MNGI Digestive Health
state: Minnesota
city: Plymouth
country: United States
facility: Minnesota Gastroenterology PA
state: Minnesota
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research - HyperCore
state: Nebraska
city: Las Vegas
country: United States
facility: Sierra Clinical Research
state: Nevada
city: Las Vegas
country: United States
facility: Office of Site 1
state: Nevada
city: Las Vegas
country: United States
facility: Office of Site 2
state: Nevada
city: Reno
country: United States
facility: Advanced Research Institute
state: Nevada
city: Englewood
country: United States
facility: The Gastroenterology Group of Northern NJ LLC
state: New Jersey
city: Freehold
country: United States
facility: Allied Health Clinical Research Organization
state: New Jersey
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: Hartsdale
country: United States
facility: Drug Trials America
state: New York
city: New York
country: United States
facility: Care Access Research
state: New York
city: Chapel Hill
country: United States
facility: UNC Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Gastroenterology and Hepatology PLLC
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research, LLC
state: North Carolina
city: Jacksonville
country: United States
facility: East Carolina Gastroenterology
state: North Carolina
city: Mount Airy
country: United States
facility: Clinical Trials of America-NC, LLC
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates LLC
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research
state: North Dakota
city: Cincinnati
country: United States
facility: Gastro Health Research
state: Ohio
city: Columbus
country: United States
facility: Remington Davis Clinical Research
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Medical Research LLC
state: Ohio
city: Westlake
country: United States
facility: North Shore Gastroenterology
state: Ohio
city: Harrisburg
country: United States
facility: Susquehanna Research Group, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Uniontown
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: East Greenwich
country: United States
facility: Velocity Clinical Research - Providence
state: Rhode Island
city: Greenville
country: United States
facility: Gastroenterology Associates, PA of Greenville
state: South Carolina
city: Cordova
country: United States
facility: Gastro One
state: Tennessee
city: Hixson
country: United States
facility: Galen Medical Group
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates Inc
state: Tennessee
city: Nashville
country: United States
facility: QUALITY Medical Research
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Digestive Disease Center
state: Tennessee
city: Brownsville
country: United States
facility: Gastroenterology Consultants of South Texas, PLLC
state: Texas
city: Carrollton
country: United States
facility: Digestive Health Associates of Texas, PA
state: Texas
city: Carrollton
country: United States
facility: Family Medicine Associates of Texas
state: Texas
city: El Paso
country: United States
facility: Texas Tech Physicians of El Paso
state: Texas
city: Garland
country: United States
facility: Digestive Health Associates of Texas, P.A.dba DHAT Research Institute
state: Texas
city: Houston
country: United States
facility: Primecare Medical Group
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic, LLC
state: Texas
city: McAllen
country: United States
facility: Rio Grande Gastroenterology
state: Texas
city: San Antonio
country: United States
facility: Quality Research Inc
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of San Antonio (GERSA)
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute LLC
state: Texas
city: Sherman
country: United States
facility: Sherman Clinical Research
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Southlake
country: United States
facility: GI Alliance
state: Texas
city: Tomball
country: United States
facility: Texas Gastro Consultants
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Salt Lake City
country: United States
facility: Kalo Clinical Research
state: Utah
city: Sandy
country: United States
facility: Advanced Research Institute
state: Utah
city: Lynchburg
country: United States
facility: Blue Ridge Medical Research
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners LLC
state: Virginia
city: Bellevue
country: United States
facility: Washington Gastroenterology
state: Washington
Study officials:
affiliation: Phathom Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: