A randomized, phase 3 multicenter study to confirm the clinical efficacy of linaprazan glurate compared to lansoprazole in participants with erosive esophagitis (EE) due to gastroesophageal reflux disease (GERD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cinclus Pharma Holding AB (publ)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

3 Oct 2025 → ongoing

Decision date (initial)

2025-08-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Cinclus Pharma Holding AB

External identifiers

EU CT number

2024-518714-31-00

WHO UTN

U1111-1315-2237

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Safety, Efficacy

To confirm superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the healing of EE due to GERD of LA grades C/D after 4 weeks of double-blind treatment.

Secondary objectives 17

1. 1. To confirm non-inferiority of linaprazan glurate 50 mg BID compared to lansoprazole in the cumulative healing of EE due to GERD in participants with all grades of esophagitis after 8 weeks of double-blind treatment.
2. 2. To confirm superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the healing of all grades of esophagitis after 4 weeks of double-blind treatment.
3. 3. To confirm non-inferiority of linaprazan glurate 50 mg BID compared to lansoprazole in percentage of 24-hour heartburn-free days after 8 weeks of treatment.
4. 4. To confirm superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the cumulative healing of EE LA grades C/D after 8 weeks of double-blind treatment.
5. 5. To confirm superiority of linaprazan glurate 50 mg BID compared to lansoprazole in the cumulative healing of all grades of esophagitis after 8 weeks of double-blind treatment.
6. 6. To confirm 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 double-blind treatment.
7. 7. To confirm non-inferiority of linaprazan glurate 50 mg QD compared to lansoprazole in the cumulative healing of all grades of esophagitis after 8 weeks of double-blind treatment.
8. 8. To confirm superiority of linaprazan glurate 50 mg QD compared to lansoprazole in the cumulative healing of EE LA grades C/D after 8 weeks of double-blind treatment.
9. 9. To confirm non-inferiority of linaprazan glurate 50 mg QD compared to lansoprazole in the healing of all grades of esophagitis after 4 weeks of double-blind treatment.
10. 10. To confirm superiority of linaprazan glurate 50 mg BID compared to lansoprazole in percentage of 24-hour heartburn-free days after 8 weeks of treatment.
11. 11. To confirm superiority of linaprazan glurate 50 mg BID compared to lansoprazole in percentage of 24-hour heartburn-free days after 4 weeks of treatment.
12. 12. To confirm non-inferiority of linaprazan glurate 50 mg QD compared to lansoprazole in percentage of 24-hour heartburn-free days after 8 weeks of treatment.
13. 13. To confirm superiority of linaprazan glurate 50 mg QD compared to lansoprazole in percentage of 24-hour heartburn-free days after 8 weeks of treatment.
14. 14. To confirm superiority of linaprazan glurate 50 mg QD compared to lansoprazole in percentage of 24-hour heartburn-free days after 4 weeks of treatment.
15. 15. To confirm superiority of linaprazan glurate 50 mg BID compared to lansoprazole in weekly mean severity of 24-hour heartburn Weeks 1 to 8.
16. 16. To confirm superiority of linaprazan glurate 50 mg QD compared to lansoprazole in weekly mean severity of 24-hour heartburn Weeks 1 to 8
17. 17. To evaluate the safety and tolerability of linaprazan glurate compared to lansoprazole.

Conditions and MedDRA coding

Erosive esophagitis (EE) due to gastroesophageal reflux disease (GERD)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 1. The participant understands and voluntarily signs an Informed Consent Form (ICF) prior to initiation of any trial-related assessments/procedures.
2. 2. Male or female participants aged 18 to 80 years, inclusive, at the time of signing the ICF.
3. 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. 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 26

1. 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. 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 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.
3. 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. 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: 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.
5. 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, 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.
6. 6. Known severe atrophic gastritis as assessed from medical history or upper endoscopy during Screening.
7. 7. Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.
8. 8. History of treatment course with lansoprazole within 2 months prior to Screening.
9. 9. Current peptic ulcer.
10. 10. Body mass index (BMI) ≤ 18 and ≥ 40 kg/m2 at Screening.
11. 11. Requiring concomitant therapy with any of the prohibited medications as defined in the protocol.
12. 12. Any planned major surgery within 16 weeks of Screening.
13. 13. 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).
14. 14. Known human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS) or test positive for HIV antibodies at Screening.
15. 15. 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.
16. 16. 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.
17. 17. 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.
18. 18. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to any component of the relevant IP, including excipients, as judged by the Investigator.
19. 19. 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.
20. 20. 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.
21. 21. 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.
22. 22. Women who are pregnant or breast feeding.
23. 23. 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.
24. 24. 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.
25. 25. 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.
26. 26. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Healing of EE at Week 4 as assessed by endoscopy in participants with Baseline EE LA grades C/D.

Secondary endpoints 8

1. 1. Cumulative healing of EE at Week 8 as assessed by endoscopy at 4 and 8 weeks.
2. 2. Healing of EE at Week 4 as assessed by endoscopy.
3. 3. Percentage of 24-hour heartburn-free days from Baseline to Week 8 based on the electronic Diary.
4. 4. Percentage of 24-hour heartburn-free days from Baseline to Week 4 based on the electronic Diary.
5. 5. Cumulative healing of EE at Week 8 as assessed by endoscopy at 4 and 8 weeks in participants with Baseline EE LA grades C/D.
6. 6. Healing of EE at Week 4 as assessed by endoscopy in participants with Baseline EE LA grades C/D.
7. 7. Change in weekly mean 24-hour heartburn severity from Baseline to Week 1, Week 4, and Week 8 based on electronic Diary.
8. 8. Safety analysis based on frequency and severity of adverse events (AEs) and any other safety signals detected.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cinclus Pharma Holding AB (publ)

Sponsor organisation

Cinclus Pharma Holding AB (publ)

Address

Kungsbron 1

City

Stockholm

Postcode

111 22

Country

Sweden

Scientific contact point

Organisation

Cinclus Pharma Holding AB (publ)

Contact name

Rikard Reneland

Public contact point

Organisation

Cinclus Pharma Holding AB (publ)

Contact name

Rikard Reneland

Third parties 3

Locations

6 EU/EEA countries · 70 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 81 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications