Clinical trial NCT04167670: Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Helicobacter Pylori Infection
Official title: A Phase 3 Randomized Multicenter Study to Evaluate the Efficacy and Safety of Open-Label Dual Therapy With Oral Vonoprazan 20 mg or Double-Blind Triple Therapy With Oral Vonoprazan 20 mg Compared to Double-Blind Triple Therapy With Oral Lansoprazole 30 mg Daily in Patients With Helicobacter Pylori Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Helicobacter Pylori Infection
Keywords: Vonoprazan
Lansoprazole
Lead sponsor: Phathom Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-11-19
Enrollment: 1046
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 compare the efficacy of Helicobacter pylori (HP) eradication with vonoprazan dual and triple therapy regimens versus lansoprazole triple therapy regimen in participants with HP infection, excluding participants who had a clarithromycin or amoxicillin resistant strain of HP at baseline.


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 sub-investigators, the participant is capable of understanding and complying with protocol requirements.
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 participant has at least one of the following clinical conditions with confirmed HP+ infection demonstrated by a positive 13C-UBT during the Screening Period.

   * Dyspepsia (i.e. pain or discomfort centered in the upper abdomen) lasting at least 2 weeks
   * A confirmed diagnosis of functional dyspepsia
   * A recent / new diagnosis of (non-bleeding) peptic ulcer
   * A history of peptic ulcer not previously treated for HP infection
   * A requirement for long-term non-steroidal anti-inflammatory drug (NSAID) treatment at a stable dose of the NSAID
5. A female participant of childbearing potential who is or may be routinely sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from the signing of informed consent until Day -2 and two forms of adequate contraception from Day -1 until 4 weeks after the last dose of study drug.

Exclusion Criteria:

1. The participant has previously been treated with any regimen to attempt to eradicate HP.
2. The participant has gastric or duodenal ulcer with endoscopic evidence of current or recent bleeding.
3. The participant has confirmed diagnosis of gastric cancer by biopsy.
4. The participant is receiving colchicine.
5. 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 screen failed from another clinical study and who has not been dosed may be considered for enrollment in this study.
6. 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 conduct of this study (e.g., spouse, parent, child, sibling) or who may have consented under duress.
7. The participant has cutaneous lupus erythematosus or systemic lupus erythematosus.
8. The participant has had clinically significant upper or lower gastrointestinal bleeding within 4 weeks prior to randomization.
9. The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.
10. 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, red or yellow ferric oxide), PPIs, amoxicillin and/or clarithromycin, or any excipients used in the 13C-UBT: mannitol, citric acid or aspartame. Skin testing may be performed according to local standard practice to confirm hypersensitivity.
11. The participant has a history of alcohol abuse, illegal drug use, or drug addiction within the 12 months prior to screening, or who regularly consume \>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 and non-prescribed medications at screening.
12. The participant is taking any excluded medications or treatments listed in the protocol.
13. 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.
14. 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 participants safety.
15. 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.
16. 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).
17. 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.
18. 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.

Primary outcomes:
measure: Percentage of Participants With Successful Helicobacter Pylori (H Pylori) Eradication in Participants Without a Clarithromycin- or Amoxicillin-resistant Strain of H Pylori at Baseline
timeFrame: Baseline to 4 weeks after the last dose of study drugs (maximum duration of treatment was 2 weeks)
Secondary outcomes:
measure: Percentage of Participants With Successful Helicobacter Pylori (H Pylori) Eradication in Participants With a Clarithromycin-resistant Strain of H Pylori at Baseline
timeFrame: Baseline to 4 weeks after the last dose of study drugs (maximum duration of treatment was 2 weeks)
measure: Percentage of All Participants With Successful Helicobacter Pylori (H Pylori) Eradication
timeFrame: Baseline to 4 weeks after the last dose of study drugs (maximum duration of treatment was 2 weeks)
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. - Alabama
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 - Lancaster - ClinEdge - PPDS
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute
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.
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-Miami
state: Florida
city: Orlando
country: United States
facility: G. 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 - ClinEdge - PPDS
state: Georgia
city: Gurnee
country: United States
facility: IL Gastroenterology Group
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Summit Digestive & Liver Disease Specialists
state: Illinois
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: Rockville
country: United States
facility: Meridian Clinical Research-(Rockville Maryland)
state: Maryland
city: Towson
country: United States
facility: Clinical Associates
state: Maryland
city: Troy
country: United States
facility: Oakland Medical Research Center
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: Office - Site 1
state: Nevada
city: Las Vegas
country: United States
facility: Office - Site 2
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: 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: 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. - Anderson
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: Ben Taub General Hospital
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. - Plano
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: San Antonio Gastroenterology Associates Clinical Trials (SAGACT PLLC)
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. - Layton
state: Utah
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital- Health Sciences Center - PPDS
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
state: Washington
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 and Consulting Center Aleksandrovska EOOD
city: Sofia
country: Bulgaria
facility: Fourth Multiprofile Hospital for Active Treatment
city: Sofia
country: Bulgaria
facility: Diagnostic- Consultative Center Convex EOOD
city: Sofia
country: Bulgaria
facility: Synexus - Medical Center Synexus Sofia EOOD
city: Stara Zagora
country: Bulgaria
facility: Synexus - Medical Centre Synexus Sofia EOOD (branch - Stara Zagora)
city: Olomouc
country: Czechia
facility: PreventaMed s.r.o.
city: Prague
country: Czechia
facility: Synexus Czech s.r.o.
city: Praha
country: Czechia
facility: MEDIC KRAL s.r.o.
city: Ústí Nad Labem
country: Czechia
facility: Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z. Oddeleni gastroenterolgie
city: Ústí Nad Orlicí
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s. Orlickoustecka nemocnice, Interni oddeleni
city: Budapest
country: Hungary
facility: Synexus (DRS) - Synexus Magyarország Kft. Budapest
city: Debrecen
country: Hungary
facility: Synexus Affiliate - Synexus Magyarorszag Kft. Debrecen
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Gyula
country: Hungary
facility: Synexus (DRS) - Synexus Magyarorszag Kft. Gyula
city: Hatvan
country: Hungary
facility: Synexus Affiliate BKS Research Kft. Hatvan
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
city: Zalaegerszeg
country: Hungary
facility: Synexus (DRS) - Synexus Magyarország Kft. Zalaegerszeg
city: Bydgoszcz
country: Poland
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
city: Bydgoszcz
country: Poland
facility: Gabinet Lekarski-Janusz Rudzinski
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: 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: Synexus - Warsaw
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: Cardiff
country: United Kingdom
facility: Synexus - Wales Clinical Research Centre
city: Chorley
country: United Kingdom
facility: Synexus - Lancashire Clinical Research Centre
city: Edgbaston
country: United Kingdom
facility: Synexus - Midlands 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: Reading
country: United Kingdom
facility: Synexus Thames Valley 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: Megraud F, Graham DY, Howden CW, Trevino E, Weissfeld A, Hunt B, Smith N, Leifke E, Chey WD. Rates of Antimicrobial Resistance in Helicobacter pylori Isolates From Clinical Trial Patients Across the US and Europe. Am J Gastroenterol. 2023 Feb 1;118(2):269-275. doi: 10.14309/ajg.0000000000002045. Epub 2022 Sep 30.
citation: Chey WD, Megraud F, Laine L, Lopez LJ, Hunt BJ, Howden CW. Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial. Gastroenterology. 2022 Sep;163(3):608-619. doi: 10.1053/j.gastro.2022.05.055. Epub 2022 Jun 6.