Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Erosive Esophagitis

Erosive Esophagitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04124926
• Other study ID #: EE-301
• Secondary ID: 2019-002579-33
• Status: Completed
• Phase: Phase 3
• Start date: October 28, 2019
• Est. completion date: August 24, 2021

Study information

• Verified date: July 2022
• Source: Phathom Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1027
• Est. completion date: August 24, 2021
• Est. primary completion date: July 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Erosive Esophagitis
• Esophagitis

Intervention

Drug:
• Vonoprazan
Over-encapsulated tablet administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.
• Lansoprazole
Over-encapsulated capsule administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.

Locations

Country	Name	City	State
Bulgaria	Multiprofile Hospital for Active Treatment Puls AD - PPDS	Blagoevgrad
Bulgaria	University Multiprofile Hospital for Active Treatment	Pleven
Bulgaria	Diagnostic-Consultative Center Aleksandrovska EOOD	Sofia
Bulgaria	Fourth Multiprofile Hospital for Active Treatment	Sofia	Sofia City
Bulgaria	Medical Center Excelsior OOD - PPDS	Sofia
Bulgaria	Second Multiprofile Hospital for Active Treatment Sofia	Sofia
Bulgaria	Synexus - Medical Center Synexus Sofia EOOD	Sofia
Bulgaria	Synexus - Medical Centre Synexus Sofia EOOD	Stara Zagora
Czechia	PreventaMed s.r.o.	Olomouc
Czechia	Synexus Czech s.r.o.	Prague
Czechia	MEDIC KRAL s.r.o.	Praha	Prague
Czechia	Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z. Oddeleni gastroenterolgie	Usti nad Labem
Czechia	Nemocnice Pardubickeho kraje, a.s. Orlickoustecka nemocnice, Interni oddeleni, Cs.	Usti nad Orlici	Pardubice
Hungary	Synexus (DRS) - Synexus Magyarország Kft. Budapest	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont Nagyerdei Krt. 98, Belgyogyaszati Klinika	Debrecen	Hajdú-Bihar
Hungary	Synexus Affiliate - Synexus Magyarorszag Kft. Debrecen	Debrecen
Hungary	Synexus (DRS) - Synexus Magyarorszag Kft. Gyula	Gyula
Hungary	Synexus Affiliate BKS Research Kft. Hatvan	Hatvan	Heves
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz	Nyíregyháza	Szabolcs-Szatmár-Bereg
Hungary	Synexus (DRS) - Synexus Magyarország Kft. Zalaegerszeg	Zalaegerszeg
Poland	Gabinet Lekarski-Janusz Rudzinski ul. Powstancow Warszawy 5	Bydgoszcz
Poland	Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy Centrum Endoskopii Zabiegowej - Poradnia Chorob Jelitowych	Bydgoszcz
Poland	Synexus - Czestochowa	Czestochowa
Poland	Synexus - Gdansk	Gdansk
Poland	Synexus - Gdynia	Gdynia
Poland	Synexus - Katowice	Katowice
Poland	Synexus Affiliate - Krakowskie Centrum Medyczne	Kraków
Poland	Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Sp. J.	Ksawerów
Poland	Santa Familia Centrum Badan Profilaktyki i Leczenia	Lódz
Poland	Synexus - Lodz	Lódz
Poland	GASTRO MED Zaklad Opieki Zdrowotnej	Lublin
Poland	Synexus - Poznan	Poznan
Poland	Korczowski Bartosz, Gabinet Lekarski	Rzeszów
Poland	Twoja Przychodnia - Szczecinskie Centrum Medyczne	Szczecin
Poland	Gastromed Specjalistyczne Centrum Gastrologii i Endoskopii	Torun
Poland	REUMATIKA - Centrum Reumatologii NZOZ	Warszawa
Poland	Synexus - Warszawa	Warszawa
Poland	Melita Medical	Wroclaw
Poland	Synexus - Wroclaw	Wroclaw
United Kingdom	Synexus - Wales Clinical Research Centre	Cardiff
United Kingdom	Synexus - Lancashire Clinical Research Centre	Chorley
United Kingdom	Synexus - Midlands Clinical Research Centre	Edgbaston	West Midlands
United Kingdom	CPS Research	Glasgow
United Kingdom	Synexus - Hexham Clinical Research Centre	Hexham
United Kingdom	Synexus - Merseyside Clinical Research Centre	Liverpool
United Kingdom	Synexus - Manchester Clinical Research Centre	Manchester
United Kingdom	Synexus Thames Valley Clinical Research Centre	Reading	Berkshire
United Kingdom	Synexus - North Tees Clinical Research Centre	Stockton-on-Tees
United States	Anaheim Clinical Trials LLC	Anaheim	California
United States	Synexus Clinical Research US, Inc.	Anderson	South Carolina
United States	Pinnacle Research Group	Anniston	Alabama
United States	North Alabama Research Center LLC	Athens	Alabama
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Nexgen Research Center	Atlanta	Georgia
United States	Inquest Clinical Research	Baytown	Texas
United States	Washington Gastroenterology	Bellevue	Washington
United States	Synexus Clinical Research US, Inc.	Birmingham	Alabama
United States	Gastroenterology Associates of Fairfield County	Bridgeport	Connecticut
United States	Connecticut Clinical Research Foundation	Bristol	Connecticut
United States	Synexus Clinical Research US, Inc. - East Valley Family Physicians, PLC	Chandler	Arizona
United States	Clinical Trials of South Carolina	Charleston	South Carolina
United States	Carolinas Research Center	Charlotte	North Carolina
United States	New River Valley Research Institute	Christiansburg	Virginia
United States	eStudySite - Chula Vista - PPDS	Chula Vista	California
United States	GW Research, Inc. - ClinEdge - PPDS	Chula Vista	California
United States	Iowa Digestive Disease Center	Clive	Iowa
United States	Synexus Clinical Research US, Inc. - Colorado Springs Family Practice	Colorado Springs	Colorado
United States	Kindred Medical Institute for Clinical Trials, LLC	Corona	California
United States	Clinical Trials Management LLC	Covington	Louisiana
United States	Synexus Clinical Research US, Inc. - Dallas	Dallas	Texas
United States	Dayton Gastroenterology, Inc	Dayton	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Riverside Clinical Research	Edgewater	Florida
United States	Texas Tech University Health Sciences Center El Paso	El Paso	Texas
United States	MediSphere Medical Research Center, LLC	Evansville	Indiana
United States	Verity Research, Inc.	Fairfax	Virginia
United States	HB Clinical Trials, Inc.	Fountain Valley	California
United States	Prestige Clinical Research	Franklin	Ohio
United States	Medication Management LLC	Greensboro	North Carolina
United States	Carolina Research	Greenville	North Carolina
United States	Illinois Gastroenterology Group	Gurnee	Illinois
United States	Drug Trials America - ClinEdge	Hartsdale	New York
United States	Synexus Clinical Research US, Inc. Site 1	Henderson	Nevada
United States	Synexus Clinical Research US, Inc. Site 2	Henderson	Nevada
United States	Peters Medical Research, LLC - ClinEdge - PPDS	High Point	North Carolina
United States	Research Centers of America - ERG	Hollywood	Florida
United States	CroNOLA, LLC.	Houma	Louisiana
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Precision Research Institute, LLC	Houston	Texas
United States	Medical Affiliated Research Center Inc	Huntsville	Alabama
United States	Nature Coast Clinical Research	Inverness	Florida
United States	ENCORE Borland-Groover Clinical Research - ERN - PPDS	Jacksonville	Florida
United States	Multi Specialty Clinical Research	Johnson City	Tennessee
United States	The Alliance for Multispecialty Research, LLC	Kansas City	Missouri
United States	OM Research LLC	Lancaster	California
United States	Las Vegas - Site 1	Las Vegas	Nevada
United States	Sierra Clinical Research - ClinEdge - PPDS	Las Vegas	Nevada
United States	Site 2	Las Vegas	Nevada
United States	Synexus Clinical Research US, Inc.	Layton	Utah
United States	Applied Research Center of Little Rock	Little Rock	Arkansas
United States	Preferred Research Partners - ClinEdge - PPDS	Little Rock	Arkansas
United States	Torrance Clinical Research Institute	Lomita	California
United States	LA County + USC Medical Center	Los Angeles	California
United States	Southern California Research Institute Medical Group, Inc.	Los Angeles	California
United States	Blue Ridge Medical Research	Lynchburg	Virginia
United States	Gastroenterology Associates of Central Georgia, LLC	Macon	Georgia
United States	Rio Grande Gastroenterology	McAllen	Texas
United States	Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC	Mesa	Arizona
United States	Synexus Clinical Research US, Inc. - Desert Clinical Research, LLC	Mesa	Arizona
United States	Clinical Trials Management LLC	Metairie	Louisiana
United States	Columbus Clinical Services LLC	Miami	Florida
United States	Jesscan Medical Research	Miami	Florida
United States	Nuren Medical and Research Center	Miami	Florida
United States	Premier Research Associate, Inc.	Miami	Florida
United States	Facey Medical Foundation	Mission Hills	California
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	Clinical Research Associates Inc	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Gastroenterology Health Partners, PLLC	New Albany	Indiana
United States	Central Sooner Research	Norman	Oklahoma
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Atria Clinical Research - BTC - PPDS	North Little Rock	Arkansas
United States	Summit Digestive & Liver Disease Specialists State Street Clinic	Oakbrook Terrace	Illinois
United States	Advanced Research Institute	Ogden	Utah
United States	Heartland Clinical Research, Inc	Omaha	Nebraska
United States	Southtowns Gastroenterology, PLLC	Orchard Park	New York
United States	Gutierrez Medical Center	Orlando	Florida
United States	Advanced Gastroenterology Associates, LLC	Palm Harbor	Florida
United States	Palmtree Clinical Research	Palm Springs	California
United States	Innovation Medical Research Center	Palmetto Bay	Florida
United States	Digestive System Healthcare	Pasadena	Texas
United States	In-Quest Medical Research, LLC	Peachtree Corners	Georgia
United States	Pearland Physicians	Pearland	Texas
United States	Elite Clinical Studies - Phoenix - BTC - PPDS	Phoenix	Arizona
United States	Hope Research Institute LLC	Phoenix	Arizona
United States	Synexus Clinical Research US, Inc. - St. Petersburg	Pinellas Park	Florida
United States	Synexus Clinical Research US, Inc.	Plano	Texas
United States	Carolina's GI Research, LLC	Raleigh	North Carolina
United States	Rapid City Medical Center LLP	Rapid City	South Dakota
United States	Advanced Research Institute	Reno	Nevada
United States	Meridian Clinical Research	Rockville	Maryland
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Gastroenterology Research of San Antonio (GERSA)	San Antonio	Texas
United States	Quality Research Inc	San Antonio	Texas
United States	Southern Star Research Institute, LLC	San Antonio	Texas
United States	Medical Associates Research Group, Inc.	San Diego	California
United States	Precision Research Institute	San Diego	California
United States	Paragon Rx Clinical, Inc.	Santa Ana	California
United States	Harborview Medical Center, University of Washington Medical Center	Seattle	Washington
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Precision Clinical Research, LLC	Sunrise	Florida
United States	Guardian Angel Research Center	Tampa	Florida
United States	Clinical Associates Research	Towson	Maryland
United States	Oakland Medical Research Center	Troy	Michigan
United States	Del Sol Research Management - BTC - PPDS	Tucson	Arizona
United States	Western States Clinical Research, Inc.	Wheat Ridge	Colorado
United States	Gastroenterology Associates of Western Michigan, PLC	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Phathom Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Hungary,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Healing Phase: Percentage of Participants Who Had Complete Healing of EE by Week 8	A participant was considered to have complete healing of EE if healing was demonstrated during endoscopy.	Week 8
Primary	Maintenance Phase: Percentage of Participants Who Maintained Complete Healing of EE at Week 24	A participant was considered to have complete healing of EE if healing was demonstrated during endoscopy.	Week 24
Secondary	Healing Phase: Percentage of 24-hour Heartburn-free Days	A 24-hour heartburn-free day was defined as a day having no heartburn among all diary entries for that day. The percentage of 24-hour heartburn-free days was calculated using all days with at least 1 evening or morning diary entry during the treatment period of this phase.	Day 1 to Week 8
Secondary	Healing Phase: Percentage of Participants With Baseline LA Classification Grades C or D Who Had Complete Healing of EE at Week 2	A participant was considered to have complete healing of EE if healing was demonstrated during endoscopy.; LA Classification of Esophagitis Grading Scale: Grade C: One or more mucosal breaks that are continuous between the tops of 2 or more mucosal folds, which involves less than 75% of the circumference.; Grade D: One or more mucosal breaks, which involves at least 75% of the circumference.	Week 2
Secondary	Healing Phase: Percentage of Participants With Onset of Sustained Resolution of Heartburn by Day 3	Sustained resolution was defined as at least 7 consecutive days with no daytime or night time heartburn as assessed by the daily diary. A participant was considered to have sustained resolution of heartburn by Day 3 if the first day of the 7 consecutive days without symptoms was on Days 1, 2, or 3.	Day 1 to maximum of Day 10 (inclusive of 7 day heartburn assessment)
Secondary	Healing Phase: Percentage of Participants With Baseline LA Classification Grades C or D Who Had Complete Healing of EE by Week 8	A participant was considered to have complete healing of EE if healing was demonstrated during endoscopy.; LA Classification of Esophagitis Grading Scale: Grade C: One or more mucosal breaks that are continuous between the tops of 2 or more mucosal folds, which involves less than 75% of the circumference.; Grade D: One or more mucosal breaks, which involves at least 75% of the circumference.	Week 8
Secondary	Healing Phase: Percentage of Participants Who Had Complete Healing of EE at Week 2	A participant was considered to have complete healing of EE if healing was demonstrated during endoscopy.	Week 2
Secondary	Maintenance Phase: Percentage of Participants With Baseline LA Classification Grades C or D Who Maintained Complete Healing of EE at Week 24	A participant was considered to have complete healing of EE if healing was demonstrated during endoscopy.; LA Classification of Esophagitis Grading Scale: Grade C: One or more mucosal breaks that are continuous between the tops of 2 or more mucosal folds, which involves less than 75% of the circumference.; Grade D: One or more mucosal breaks, which involves at least 75% of the circumference.	Week 24
Secondary	Maintenance Phase: Percentage of 24-hour Heartburn-free Days	A 24-hour heartburn-free day was defined as a day having no heartburn among all diary entries for that day. The percentage of 24-hour heartburn-free days was calculated using all days with at least 1 evening or morning diary entry during the treatment period of this phase.	Day 1 to Week 24