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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04124926
Recruitment Status : Active, not recruiting
First Posted : October 14, 2019
Last Update Posted : January 15, 2021
Sponsor:
Information provided by (Responsible Party):
Phathom Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Erosive Esophagitis Drug: Vonoprazan Drug: Lansoprazole Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1027 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : October 28, 2019
Estimated Primary Completion Date : July 25, 2021
Estimated Study Completion Date : August 25, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Healing Phase: Vonoprazan 20 mg
Participants will receive oral vonoprazan 20 mg once per day (QD) for a maximum of 8 weeks.
Drug: Vonoprazan
Over-encapsulated tablet administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.

Active Comparator: Healing Phase: Lansoprazole 30 mg
Participants will receive oral lansoprazole 30 mg once per day (QD) for a maximum of 8 weeks.
Drug: Lansoprazole
Over-encapsulated capsule administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.

Experimental: Maintenance Phase: Vonoprazan 10 mg
Participants will receive oral vonoprazan 10 mg once per day (QD) for a maximum of 24 weeks.
Drug: Vonoprazan
Over-encapsulated tablet administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.

Experimental: Maintenance Phase: Vonoprazan 20 mg
Participants will receive oral vonoprazan 20 mg once per day (QD) for a maximum of 24 weeks.
Drug: Vonoprazan
Over-encapsulated tablet administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.

Active Comparator: Maintenance Phase: Lansoprazole 15 mg
Participants will receive oral lansoprazole 15 mg once per day (QD) for a maximum of 24 weeks.
Drug: Lansoprazole
Over-encapsulated capsule administered orally with approximately 240 mL water, 30 minutes prior to the morning meal.




Primary Outcome Measures :
  1. Healing Phase: Number of participants who have complete healing of erosive esophagitis (EE) by Week 8 [ Time Frame: Week 8 ]
    A participant will be considered to have complete healing of EE if healing is demonstrated during endoscopy.

  2. Maintenance Phase: Number of participants who maintain complete healing of erosive esophagitis (EE) until Week 24 [ Time Frame: Day 1 to Week 24 ]
    A participant will be considered to have complete healing of EE if healing is demonstrated during endoscopy.


Secondary Outcome Measures :
  1. Healing Phase: Number of participants who have complete healing of erosive esophagitis (EE) by Week 2 [ Time Frame: Week 2 ]
    A participant will be considered to have complete healing of EE if healing is demonstrated during endoscopy.

  2. Healing Phase: Number of participants with baseline LA Classification Grades C or D who have complete healing of erosive esophagitis (EE) by Week 2 [ Time Frame: Week 2 ]

    A participant will be considered to have complete healing of EE if healing is demonstrated during endoscopy.

    LA Classification 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.

    LA Classification Grade D: One or more mucosal breaks, which involves at least 75% of the circumference.


  3. Healing Phase: Number of participants with baseline LA Classification Grades C or D who have complete healing of erosive esophagitis (EE) by Week 8 [ Time Frame: Week 8 ]

    A participant will be considered to have complete healing of EE if healing is demonstrated during endoscopy.

    LA Classification 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.

    LA Classification Grade D: One or more mucosal breaks, which involves at least 75% of the circumference.


  4. Healing Phase: Percentage of 24 hour heartburn free days [ Time Frame: Day 1 to Week 8 ]
  5. Healing Phase: Number of participants with onset of sustained resolution of heartburn by Day 3 [ Time Frame: Day 1 to maximum of Day 10 (inclusive of 7 day heartburn assessment) ]
    Sustained resolution is defined as at least 7 consecutive days with no daytime or nighttime heartburn as assessed by the daily diary. Participants will be considered to have sustained resolution of heartburn by Day 3 if the first day of the 7 consecutive days without symptoms is on Days 1, 2, or 3.

  6. Maintenance Phase: Number of participants with baseline LA Classification Grades C or D who maintain complete healing of erosive esophagitis (EE) until Week 24 [ Time Frame: Day 1 to Week 24 ]

    A participant will be considered to have complete healing of EE if healing is demonstrated during endoscopy.

    LA Classification 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.

    LA Classification Grade D: One or more mucosal breaks, which involves at least 75% of the circumference.


  7. Maintenance Phase: Percentage of 24 hour heartburn free days [ Time Frame: Day 1 to Week 24 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04124926


Locations
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Sponsors and Collaborators
Phathom Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Phathom Pharmaceuticals
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Responsible Party: Phathom Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04124926    
Other Study ID Numbers: EE-301
2019-002579-33 ( EudraCT Number )
First Posted: October 14, 2019    Key Record Dates
Last Update Posted: January 15, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data from this study will be published; however, it is undecided if patient level data will be made available at this time.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Phathom Pharmaceuticals, Inc.:
Erosive Esophagitis
Vonoprazan
Lansoprazole
Additional relevant MeSH terms:
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Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Lansoprazole
Dexlansoprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action