A Study Comparing the Effect and Safety of Linaprazan Glurate to Lansoprazole in Participants With Erosive Esophagitis (EE) Due to Gastroesophageal Reflux Disease (GERD)

Cinclus Pharma

Status and phase: Begins enrollment in 1 month; Phase 3

Conditions: GERD (Gastroesophageal Reflux Disease)

Treatments: Drug: Linaprazan glurate 50 mg Twice Daily (BID); Drug: Lansoprazole 30 mg Once Daily (QD); Drug: Linaprazan Glurate 50 mg Once Daily (QD)

Study type: Interventional

Funder types: Industry

Identifiers

NCT07037875

CX842A2301

IND 149483 (Other Identifier)

2024-518714-31-00 (EU Trial (CTIS) Number)

UTN U1111-1315-2237 (Other Identifier)

Details and patient eligibility

About

The goal of this clinical trial is to find out how well linaprazan glurate can heal erosive esophagitis (EE) caused by gastroesophageal reflux disease (GERD), compared to lansoprazole, a commonly used medication. Researchers will also evaluate whether linaprazan glurate:

• Reduces heartburn symptoms more effectively than lansoprazole
• Is safe and well tolerated, based on physical exams, blood tests, and vital signs (heart rate, blood pressure, temperature, and breathing rate)
• Causes any side effects during treatment
• Has different effects depending on how much of the drug is in the blood
• Works differently depending on participants' genes

Participants must be between 18 to 80 years old and have EE due to GERD confirmed by an endoscopy. Participants cannot join if they have an active Helicobacter pylori (HP) infection or were treated for HP in the past 6 weeks or have taken antibiotics or bismuth-containing drugs in the past 6 weeks.

The study is a randomized, double-blind, active comparator-controlled trial lasting up to 4 months. Randomized means that participants are assigned by chance (like flipping a coin) to one of the treatment groups and double-blind means neither the participants nor the study team will know which treatment is given. Participants will be placed into one of three groups (about 167 people in each group):

• Linaprazan glurate 50 mg twice a day
• Linaprazan glurate 50 mg once a day
• Lansoprazole 30 mg once a day

Everyone will take 2 tablets and 1 capsule by mouth daily for 8 weeks. Some tablets or capsules will be placebos (look like medicine but contain no active drug). Participants will:

• Undergo an endoscopy in the beginning and after 4 weeks of treatment
• If healing is not observed, another endoscopy may be done at 8 weeks
• During the procedure, doctors will use a thin, flexible tube with a camera to look at the esophagus and take small tissue samples (biopsies)
• Have blood and urine tests at clinic visits to check overall health
• Receive electrocardiograms (ECGs) to monitor heart function
• Complete daily questionnaires on an electronic device about symptoms and experiences

Enrollment: 500 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. The participant understands and voluntarily signs an Informed Consent Form (ICF) prior to initiation of any study-related assessments/procedures.
2. Male or female participants aged 18 to 80 years, inclusive, at the time of signing the ICF.
3. 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.).
4. 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

1. 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.

2. 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 study, or influence the study results or the participant's ability to participate in the study. The following examples are conditions that would exclude the patient from participating:

   1. History of recent myocardial infarction/acute coronary syndrome.
   2. History of ventricular arrhythmia or implanted cardioverter defibrillator.
   3. Symptomatic congestive heart failure (New York Heart Association class 3-4).
   4. Family history of/diagnosis of hereditary arrhythmia syndrome.
   5. History of adult asthma that required intensive treatment in an emergency room.

3. 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.

4. 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: Patients 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.

5. 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, gastroenterostomy, any bariatric surgery, bowel resection, or transjugular intrahepatic portosystemic shunt. Nissen fundoplication is not exclusionary as long as the patient is eligible according to other criteria.

6. Known severe atrophic gastritis as assessed from medical history or upper endoscopy during Screening.

7. Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.

8. History of treatment course with lansoprazole within 2 months prior to Screening.

9. Current peptic ulcer.

10. Body mass index (BMI) ≤ 18 and ≥ 40 kg/m² at Screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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500 participants in 3 patient groups

Group 1: Linaprazan glurate 50 mg BID

Experimental group

Treatment:

Drug: Linaprazan glurate 50 mg Twice Daily (BID)

Group 2: Linaprazan glurate 50 mg QD

Experimental group

Treatment:

Drug: Linaprazan Glurate 50 mg Once Daily (QD)

Group 3: Lansoprazole 30 mg QD

Active Comparator group

Treatment:

Drug: Lansoprazole 30 mg Once Daily (QD)