Clinical trial NCT04124926: Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Erosive Esophagitis
Official title: A Phase 3, Randomized, Double-Blind, Two Phase, Multicenter Study to Evaluate the Efficacy and Safety of Vonoprazan 20 mg Compared to Lansoprazole 30 mg for Healing in Patients With Erosive Esophagitis and to Evaluate the Efficacy and Safety of Vonoprazan (10 mg and 20 mg) Compared to Lansoprazole 15 mg for the Maintenance of Healing in Patients With Healed Erosive Esophagitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Erosive Esophagitis
Keywords: Erosive Esophagitis
Vonoprazan
Lansoprazole
Lead sponsor: Phathom Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-14
Enrollment: 1027
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: 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.

Primary outcomes:
measure: Healing Phase: Percentage of Participants Who Had Complete Healing of EE by Week 8
timeFrame: Week 8
measure: Maintenance Phase: Percentage of Participants Who Maintained Complete Healing of EE at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Healing Phase: Percentage of 24-hour Heartburn-free Days
timeFrame: Day 1 to Week 8
measure: Healing Phase: Percentage of Participants With Baseline LA Classification Grades C or D Who Had Complete Healing of EE at Week 2
timeFrame: Week 2
measure: Healing Phase: Percentage of Participants With Onset of Sustained Resolution of Heartburn by Day 3
timeFrame: Day 1 to maximum of Day 10 (inclusive of 7 day heartburn assessment)
measure: Healing Phase: Percentage of Participants With Baseline LA Classification Grades C or D Who Had Complete Healing of EE by Week 8
timeFrame: Week 8
measure: Healing Phase: Percentage of Participants Who Had Complete Healing of EE at Week 2
timeFrame: Week 2
measure: Maintenance Phase: Percentage of Participants With Baseline LA Classification Grades C or D Who Maintained Complete Healing of EE at Week 24
timeFrame: Week 24
measure: Maintenance Phase: Percentage of 24-hour Heartburn-free Days
timeFrame: Day 1 to Week 24
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Athens
country: United States
facility: North Alabama Research Center LLC
state: Alabama
city: Birmingham
country: United States
facility: Synexus Clinical Research US, Inc.
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center Inc
state: Alabama
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc. - East Valley Family Physicians, PLC
state: Arizona
city: Mesa
country: United States
facility: Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC
state: Arizona
city: Mesa
country: United States
facility: Synexus Clinical Research US, Inc. - Desert Clinical Research, LLC
state: Arizona
city: Phoenix
country: United States
facility: Elite Clinical Studies - Phoenix - BTC - PPDS
state: Arizona
city: Phoenix
country: United States
facility: Hope Research Institute LLC
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management - BTC - PPDS
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners - ClinEdge - PPDS
state: Arkansas
city: Little Rock
country: United States
facility: Applied Research Center of Little Rock
state: Arkansas
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: North Little Rock
country: United States
facility: Atria Clinical Research - BTC - PPDS
state: Arkansas
city: Anaheim
country: United States
facility: Anaheim Clinical Trials LLC
state: California
city: Chula Vista
country: United States
facility: GW Research, Inc. - ClinEdge - PPDS
state: California
city: Chula Vista
country: United States
facility: eStudySite - Chula Vista - PPDS
state: California
city: Corona
country: United States
facility: Kindred Medical Institute for Clinical Trials, LLC
state: California
city: Fountain Valley
country: United States
facility: HB Clinical Trials, Inc.
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: Los Angeles
country: United States
facility: LA County + USC Medical Center
state: California
city: Los Angeles
country: United States
facility: Southern California Research Institute Medical Group, Inc.
state: California
city: Mission Hills
country: United States
facility: Facey Medical Foundation
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research
state: California
city: San Diego
country: United States
facility: Precision Research Institute
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: Colorado Springs
country: United States
facility: Synexus Clinical Research US, Inc. - Colorado Springs Family Practice
state: Colorado
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 Foundation
state: Connecticut
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America - ERG
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 - ERN - PPDS
state: Florida
city: Miami
country: United States
facility: Columbus Clinical Services LLC
state: Florida
city: Miami
country: United States
facility: Jesscan Medical Research
state: Florida
city: Miami
country: United States
facility: Nuren Medical and Research Center
state: Florida
city: Miami
country: United States
facility: Premier Research Associate, Inc.
state: Florida
city: Orlando
country: United States
facility: Gutierrez Medical Center
state: Florida
city: Palm Harbor
country: United States
facility: Advanced Gastroenterology Associates, LLC
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center
state: Florida
city: Pinellas Park
country: United States
facility: Synexus Clinical Research US, Inc. - St. Petersburg
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research, LLC
state: Florida
city: Tampa
country: United States
facility: Guardian Angel Research Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Atlanta
country: United States
facility: Nexgen Research Center
state: Georgia
city: Macon
country: United States
facility: Gastroenterology Associates of Central Georgia, LLC
state: Georgia
city: Peachtree Corners
country: United States
facility: In-Quest Medical Research, LLC
state: Georgia
city: Gurnee
country: United States
facility: Illinois Gastroenterology Group
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Summit Digestive & Liver Disease Specialists State Street Clinic
state: Illinois
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC
state: Indiana
city: New Albany
country: United States
facility: Gastroenterology Health Partners, PLLC
state: Indiana
city: Clive
country: United States
facility: Iowa Digestive Disease Center
state: Iowa
city: Covington
country: United States
facility: Clinical Trials Management LLC
state: Louisiana
city: Houma
country: United States
facility: CroNOLA, LLC.
state: Louisiana
city: Metairie
country: United States
facility: Clinical Trials Management LLC
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Rockville
country: United States
facility: Meridian Clinical Research
state: Maryland
city: Towson
country: United States
facility: Clinical Associates Research
state: Maryland
city: Troy
country: United States
facility: Oakland Medical Research Center
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, PLC
state: Michigan
city: Kansas City
country: United States
facility: The Alliance for Multispecialty Research, LLC
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Heartland Clinical Research, Inc
state: Nebraska
city: Henderson
country: United States
facility: Synexus Clinical Research US, Inc. Site 1
state: Nevada
city: Henderson
country: United States
facility: Synexus Clinical Research US, Inc. Site 2
state: Nevada
city: Las Vegas
country: United States
facility: Sierra Clinical Research - ClinEdge - PPDS
state: Nevada
city: Las Vegas
country: United States
facility: Site 2
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas - Site 1
state: Nevada
city: Reno
country: United States
facility: Advanced Research Institute
state: Nevada
city: Hartsdale
country: United States
facility: Drug Trials America - ClinEdge
state: New York
city: Orchard Park
country: United States
facility: Southtowns Gastroenterology, PLLC
state: New York
city: Charlotte
country: United States
facility: Carolinas Research Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: Medication Management LLC
state: North Carolina
city: Greenville
country: United States
facility: Carolina Research
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research, LLC - ClinEdge - PPDS
state: North Carolina
city: Raleigh
country: United States
facility: Carolina's GI Research, LLC
state: North Carolina
city: Dayton
country: United States
facility: Dayton Gastroenterology, Inc
state: Ohio
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Norman
country: United States
facility: Central Sooner Research
state: Oklahoma
city: Anderson
country: United States
facility: Synexus Clinical Research US, Inc.
state: South Carolina
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Medical Center LLP
state: South Dakota
city: Johnson City
country: United States
facility: Multi Specialty Clinical Research
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates Inc
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Baytown
country: United States
facility: Inquest Clinical Research
state: Texas
city: Dallas
country: United States
facility: Synexus Clinical Research US, Inc. - Dallas
state: Texas
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center El Paso
state: Texas
city: Houston
country: United States
facility: Precision Research Institute, LLC
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: Pasadena
country: United States
facility: Digestive System Healthcare
state: Texas
city: Pearland
country: United States
facility: Pearland Physicians
state: Texas
city: Plano
country: United States
facility: Synexus Clinical Research US, Inc.
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: Layton
country: United States
facility: Synexus Clinical Research US, Inc.
state: Utah
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Christiansburg
country: United States
facility: New River Valley Research Institute
state: Virginia
city: Fairfax
country: United States
facility: Verity Research, Inc.
state: Virginia
city: Lynchburg
country: United States
facility: Blue Ridge Medical Research
state: Virginia
city: Bellevue
country: United States
facility: Washington Gastroenterology
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center, University of Washington Medical Center
state: Washington
city: Sofia
country: Bulgaria
facility: Fourth Multiprofile Hospital for Active Treatment
state: Sofia City
city: Blagoevgrad
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Puls AD - PPDS
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment
city: Sofia
country: Bulgaria
facility: Second Multiprofile Hospital for Active Treatment Sofia
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior OOD - PPDS
city: Sofia
country: Bulgaria
facility: Diagnostic-Consultative Center Aleksandrovska EOOD
city: Sofia
country: Bulgaria
facility: Synexus - Medical Center Synexus Sofia EOOD
city: Stara Zagora
country: Bulgaria
facility: Synexus - Medical Centre Synexus Sofia EOOD
city: Usti nad Orlici
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s. Orlickoustecka nemocnice, Interni oddeleni, Cs.
state: Pardubice
city: Praha
country: Czechia
facility: MEDIC KRAL s.r.o.
state: Prague
city: Olomouc
country: Czechia
facility: PreventaMed s.r.o.
city: Prague
country: Czechia
facility: Synexus Czech s.r.o.
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z. Oddeleni gastroenterolgie
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Nagyerdei Krt. 98, Belgyogyaszati Klinika
state: Hajdú-Bihar
city: Hatvan
country: Hungary
facility: Synexus Affiliate BKS Research Kft. Hatvan
state: Heves
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
state: Szabolcs-Szatmár-Bereg
city: Budapest
country: Hungary
facility: Synexus (DRS) - Synexus Magyarország Kft. Budapest
city: Debrecen
country: Hungary
facility: Synexus Affiliate - Synexus Magyarorszag Kft. Debrecen
city: Gyula
country: Hungary
facility: Synexus (DRS) - Synexus Magyarorszag Kft. Gyula
city: Zalaegerszeg
country: Hungary
facility: Synexus (DRS) - Synexus Magyarország Kft. Zalaegerszeg
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy Centrum Endoskopii Zabiegowej - Poradnia Chorob Jelitowych
city: Bydgoszcz
country: Poland
facility: Gabinet Lekarski-Janusz Rudzinski ul. Powstancow Warszawy 5
city: Czestochowa
country: Poland
facility: Synexus - Czestochowa
city: Gdańsk
country: Poland
facility: Synexus - Gdansk
city: Gdynia
country: Poland
facility: Synexus - Gdynia
city: Katowice
country: Poland
facility: Synexus - Katowice
city: Kraków
country: Poland
facility: Synexus Affiliate - Krakowskie Centrum Medyczne
city: Ksawerów
country: Poland
facility: Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Sp. J.
city: Lublin
country: Poland
facility: GASTRO MED Zaklad Opieki Zdrowotnej
city: Poznań
country: Poland
facility: Synexus - Poznan
city: Rzeszów
country: Poland
facility: Korczowski Bartosz, Gabinet Lekarski
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecińskie Centrum Medyczne
city: Toruń
country: Poland
facility: Gastromed Specjalistyczne Centrum Gastrologii i Endoskopii
city: Warszawa
country: Poland
facility: REUMATIKA - Centrum Reumatologii NZOZ
city: Warszawa
country: Poland
facility: Synexus - Warszawa
city: Wrocław
country: Poland
facility: Synexus - Wroclaw
city: Wrocław
country: Poland
facility: Melita Medical
city: Łódź
country: Poland
facility: Synexus - Lodz
city: Łódź
country: Poland
facility: Santa Familia Centrum Badań Profilaktyki i Leczenia
city: Reading
country: United Kingdom
facility: Synexus Thames Valley Clinical Research Centre
state: Berkshire
city: Edgbaston
country: United Kingdom
facility: Synexus - Midlands Clinical Research Centre
state: West Midlands
city: Cardiff
country: United Kingdom
facility: Synexus - Wales Clinical Research Centre
city: Chorley
country: United Kingdom
facility: Synexus - Lancashire Clinical Research Centre
city: Glasgow
country: United Kingdom
facility: CPS Research
city: Hexham
country: United Kingdom
facility: Synexus - Hexham Clinical Research Centre
city: Liverpool
country: United Kingdom
facility: Synexus - Merseyside Clinical Research Centre
city: Manchester
country: United Kingdom
facility: Synexus - Manchester Clinical Research Centre
city: Stockton-on-Tees
country: United Kingdom
facility: Synexus - North Tees Clinical Research Centre
Study officials:
affiliation: Phathom Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Laine L, DeVault K, Katz P, Mitev S, Lowe J, Hunt B, Spechler S. Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial. Gastroenterology. 2023 Jan;164(1):61-71. doi: 10.1053/j.gastro.2022.09.041. Epub 2022 Oct 10.