Evaluation of Linaprazan Glurate Versus Lansoprazole in Healing Erosive Esophagitis Due to Gastroesophageal Reflux Disease: A Phase 3 Randomized Controlled Trial
- Trial ID
- 2024-518714-31-00
- Protocol
- CX842A2301
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to confirm the **superiority** of linaprazan glurate 50 mg BID compared to lansoprazole in the healing of erosive esophagitis (EE) due to gastroesophageal reflux disease (GERD) of Los Angeles (LA) grades C/D after 4 weeks of double-blind treatment. This is clinically relevant as it aims to establish a more effective treatment option for patients with severe grades of esophagitis, potentially improving patient outcomes and quality of life.
Secondary objectives include:
- Confirming the non-inferiority of linaprazan glurate 50 mg BID compared to lansoprazole in the cumulative healing of EE due to GERD in patients with all grades of esophagitis after 8 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the healing of all grades of esophagitis after 4 weeks of treatment.
- Confirming the non-inferiority of linaprazan glurate 50 mg BID compared to lansoprazole in the percentage of 24-hour heartburn-free days after 8 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the cumulative healing of EE LA grades C/D after 8 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the cumulative healing of all grades of esophagitis after 8 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg QD compared to lansoprazole in the healing of EE due to GERD of LA C/D after 4 weeks of treatment.
- Confirming the non-inferiority of linaprazan glurate 50 mg QD compared to lansoprazole in the cumulative healing of all grades of esophagitis after 8 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg QD compared to lansoprazole in the cumulative healing of EE LA grades C/D after 8 weeks of treatment.
- Confirming the non-inferiority of linaprazan glurate 50 mg QD compared to lansoprazole in the healing of all grades of esophagitis after 4 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the percentage of 24-hour heartburn-free days after 8 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the percentage of 24-hour heartburn-free days after 4 weeks of treatment.
- Confirming the non-inferiority of linaprazan glurate 50 mg QD compared to lansoprazole in the percentage of 24-hour heartburn-free days after 8 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg QD compared to lansoprazole in the percentage of 24-hour heartburn-free days after 8 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg QD compared to lansoprazole in the percentage of 24-hour heartburn-free days after 4 weeks of treatment.
- Confirming the superiority of linaprazan glurate 50 mg BID compared to lansoprazole in weekly mean severity of 24-hour heartburn from Weeks 1 to 8.
- Confirming the superiority of linaprazan glurate 50 mg QD compared to lansoprazole in weekly mean severity of 24-hour heartburn from Weeks 1 to 8.
- Evaluating the safety and tolerability of linaprazan glurate compared to lansoprazole.
Participants
The clinical trial involves a total of **118 participants** diagnosed with **erosive esophagitis (EE)** due to **gastroesophageal reflux disease (GERD)**. The study population comprises both male and female subjects, aged between **18 to 80 years**, who have been endoscopically confirmed to have EE of Los Angeles (LA) grades A to D. Participants were selected based on their ability to understand and voluntarily sign an Informed Consent Form, as well as their willingness to comply with all protocol requirements. The trial does not include a vulnerable population. No specific lifestyle considerations such as diet or physical activity were highlighted in the selection criteria. The primary objective of the study is to evaluate the efficacy of linaprazan glurate compared to lansoprazole in the healing of EE after a 4-week treatment period.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **double-dummy**, active comparator-controlled, multicenter study. The primary objective is to evaluate the efficacy and safety of two doses of **linaprazan glurate** compared to **lansoprazole** in the healing of **erosive esophagitis** (EE) due to **gastroesophageal reflux disease** (GERD) of Los Angeles (LA) grades A to D. The trial is set to commence on August 15, 2025, with an estimated completion date of January 31, 2027. The study will involve participants aged 18 to 80 years who have endoscopically confirmed EE due to GERD of LA grades A to D.
Participants will be randomly assigned to receive either linaprazan glurate or lansoprazole, with matching placebos to maintain blinding. The trial will last for a maximum of 59 days, during which participants will undergo a series of study visits. The initial visit will be a screening visit to confirm eligibility, including endoscopic confirmation of EE. Subsequent visits will include assessments at Week 4 and Week 8, where the primary endpoint of healing of EE at Week 4 will be evaluated through endoscopy. Secondary endpoints include cumulative healing at Week 8, percentage of 24-hour heartburn-free days, and safety analysis based on adverse events.
Participants are expected to be involved in the study for the full duration unless conditions arise that necessitate early termination, such as non-compliance with the study protocol or the occurrence of significant adverse events. The study is structured to ensure rigorous assessment of the investigational product's efficacy and safety, with all procedures conducted in accordance with ethical standards and regulatory requirements.
Treatment
The clinical trial involves the administration of **Linaprazan glurate**, an experimental medication formulated as a tablet. The active substance, linaprazan glurate, is chemically synthesized and is provided by Cinclus Pharma Holding AB. The medication is administered orally with a maximum daily dose of 100 mg and a total maximum dose of 5900 mg over a treatment period of 59 days. The dosing schedule involves twice-daily administration (BID) to evaluate its efficacy in the healing of erosive esophagitis (EE) due to gastroesophageal reflux disease (GERD) of Los Angeles grades A to D.
In addition to the experimental treatment, the study includes a **placebo** designed to match the appearance of Linaprazan glurate 50 mg tablets. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know which treatment is being administered, thereby reducing bias in the study results.
The trial also employs **Lansoprazole** as an active comparator. Lansoprazole is provided in capsule form and is administered orally. The maximum daily dose for lansoprazole is 30 mg, with a total maximum dose of 1770 mg over the same 59-day treatment period. For blinding purposes, lansoprazole capsules are over-encapsulated to ensure that they are indistinguishable from the placebo and the experimental medication.
A **placebo** to match Lansoprazole 30 mg is also included in the study. This placebo is used to maintain the double-dummy design of the trial, which allows for the comparison of the experimental treatment with the active comparator while ensuring that all participants receive a similar treatment experience.
Efficacy
The efficacy of the investigational product, **linaprazan glurate**, will be assessed in a randomized, phase 3, double-blind, double-dummy, active comparator-controlled multicenter study. The primary endpoint for evaluating efficacy is the healing of **erosive esophagitis (EE)** at Week 4, as assessed by endoscopy in participants with baseline EE of Los Angeles (LA) grades C/D. Secondary endpoints include cumulative healing of EE at Week 8, healing of EE at Week 4, and the percentage of 24-hour heartburn-free days from Baseline to Week 8 and Week 4, all based on assessments through endoscopy and electronic diaries.
Endoscopic evaluations will be conducted at specified timepoints, namely at Week 4 and Week 8, to determine the healing status of EE. The percentage of heartburn-free days will be recorded using an electronic diary, providing patient-reported outcomes that contribute to the assessment of efficacy. The change in weekly mean 24-hour heartburn severity from Baseline to Week 1, Week 4, and Week 8 will also be evaluated using data collected from the electronic diary. These assessments will be analyzed to confirm the superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the healing of EE due to **gastroesophageal reflux disease (GERD)** of LA grades C/D after 4 weeks of double-blind treatment.
Inclusion and Exclusion Criteria
Inclusion Criteria
- The participant understands and voluntarily signs an Informed Consent Form (ICF) prior to initiation of any trial-related assessments/procedures.
- Male or female participants aged 18 to 80 years, inclusive, at the time of signing the ICF.
- The participant is willing and able to comply with all aspects of the protocol (including endoscopies, PK sampling, tablet and capsule swallowing, electronic device [e-device] completion, etc.).
- The participant has endoscopically confirmed EE due to GERD of LA grades A to D during the Screening Period as assessed in Central Review by an Independent Review Committee (IRC).
Exclusion Criteria
- Ongoing infection with HP or diagnosis and treatment of HP infection within 6 weeks of randomization OR any treatment with antibiotics or bismuth containing drugs within 6 weeks of randomization.
- History or presence of any clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, neurological disease or disorder, or psychiatric diagnosis which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or influence the trial results or the participant’s ability to participate in the trial. The following examples are conditions that would exclude the participant from participating: a. History of myocardial infarction/acute coronary syndrome within 3 months prior to Screening. b. History of ventricular arrhythmia or implanted cardioverter defibrillator. c. Symptomatic congestive heart failure (New York Heart Association class 3-4). d. Family history of/diagnosis of hereditary arrhythmia syndrome. e. History of adult asthma that required intensive treatment in an emergency room.
- History of malignancy of any organ system (other than completely treated localized basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or in situ cervical carcinoma), within the past 5 years.
- Solitary esophageal ulcer in the proximal two-thirds of the esophagus, untreated Barrett’s esophagus or 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. *Note: Participants with diagnosis of Schatzki's ring (mucosal tissue ring around lower esophageal sphincter) are eligible to participate, unless history of dilatation within 3 months of Screening.
- History of any surgical or medical condition which might significantly alter the GERD status or the absorption, distribution, metabolism, or excretion of drugs. The Investigator is to be guided by evidence of any of the following: history of major GI surgery such as gastrectomy, any bariatric surgery, gastroenterostomy, bowel resection, or transjugular intrahepatic portosystemic shunt. Nissen fundoplication is not exclusionary as long as the participant is eligible according to other criteria.
- Known severe atrophic gastritis as assessed from medical history or upper endoscopy during Screening.
- Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.
- History of treatment course with lansoprazole within 2 months prior to Screening.
- Current peptic ulcer.
- Body mass index (BMI) ≤ 18 and ≥ 40 kg/m2 at Screening.
- Requiring concomitant therapy with any of the prohibited medications as defined in the protocol.
- Any planned major surgery within 16 weeks of Screening.
- Any clinically significant laboratory parameter outside reference value that, in the opinion of the Investigator, may suggest a new or insufficiently understood disease, may present an unreasonable risk to the participant as a result of his/her participation in the trial, or may interfere with trial assessments. Any of these Screening laboratory test results are exclusionary, but re-test is allowed: a. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 × the upper limit of normal (ULN) for the central laboratory conducting the test. b. Serum total bilirubin (TBL) >1.5 × ULN for the central laboratory conducting the test (individuals with Gilbert’s syndrome can be included). c. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 (as calculated by the central laboratory using the Modification of Diet in Renal Disease [MDRD] equation).
- Known human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS) or test positive for HIV antibodies at Screening.
- Known chronic/active viral hepatitis or test positive at Screening for hepatitis B virus (HBV: hepatitis B surface antigen [HBsAg] and/or hepatitis B core antigen [anti-HBc], with detectable HBV DNA) or hepatitis C virus (HCV: positive hepatitis C antibody [anti-HCV], with detectable HCV ribonucleic acid [RNA]). Participants with positive screening HBV or HCV serology, but with undetectable/negative HBV DNA or HCV RNA viral load are permitted to participate.
- History of long QTc syndrome (e.g., QTc ≥ 450 ms for males and ≥ 470 ms for females) or discovery of long QTc syndrome at Screening, as calculated by the Fridericia formula (QTc = QT / RR1/3) as reviewed and interpreted by a central reader.
- Cardiac arrhythmias or any clinically significant abnormalities in the resting 12-lead ECG at the time of Screening, as reviewed and interpreted on site by the Investigator and by a central reader.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to any component of the relevant IP, including excipients, as judged by the Investigator.
- Treatment with any investigational drug within 3 months prior to the first dose of the IP in this trial or is currently enrolled in another interventional clinical trial. Enrollment in the trial CX842A2303, which aims to study the maintenance of healing, is allowed while still participating in follow-up of the current trial.Enrollment in the trial CX842A2303, which aims to study the maintenance of healing, is allowed while still participating in follow-up of the current trial. Enrollment in the trial CX842A2303, which aims to study the maintenance of healing, is allowed while still participating in follow-up of the current trial.
- Positive screen for drugs of abuse at Screening (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates). Eligibility in trial participation will be assessed by the Investigator.
- Current or history of alcohol, drug abuse, and/or use of androgens/anabolic steroids (testosterone and testosterone esters [enanthate, undecanoate, cypionate], methyltestosterone, oxandrolone, stanozolol, fluoxymesterone, danazol, tetrahydrogestrinone, 7α-methyl-19-nortestosterone) within 2 years prior to Screening. Stable androgen substitution treatment for male hypogonadism is allowed.
- Women who are pregnant or breast feeding.
- Individual is an employee of the Investigator, trial site, Sponsor, or Contract Research Organization (CRO) with direct involvement in the proposed trial or other trials under the direction of that Investigator, trial site, Sponsor, or CRO, as well as family members of the employee of the Investigator, trial site, Sponsor, or CRO.
- Individuals who have previously participated (completed or withdrawn) in this trial. Note: rescreening is permitted under circumstances specified in the protocol, but never for participants who have undergone randomization.
- A female participant of childbearing potential who is or may be sexually active with a non-sterilized male partner and who is unwilling to routinely use highly effective contraception from the signing of informed consent until 7 days after the last dose of IP.
- A male participant with a partner of childbearing potential who is unwilling to routinely use highly effective contraception and is unwilling to remain abstinent from the signing of informed consent until at least 7 days after the last dose of IP.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 15 Aug 2025 | 127 |
 Czechia | Not Recruiting | 15 Aug 2025 | 27 |
 Germany | Not Recruiting | 15 Aug 2025 | 5 |
 Hungary | Not Recruiting | 15 Aug 2025 | 21 |
 Poland | Not Recruiting | 15 Aug 2025 | 222 |
 Romania | Not Recruiting | 15 Aug 2025 | 9 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo to match Linaprazan glurate 50mg | Placebo | N/A | — | — | — | N/A |
Linaprazan glurate | Test | TABLET | ORAL USE | 100 | 59 | PRD11652791 |
Placebo to match Lansoprazole 30 mg | Placebo | N/A | — | — | — | N/A |
LANSOPRAZOLE | Comparator | — | ORAL USE | 30 | 59 | SUB08403MIG |