Efficacy and Safety of Rifasutenizol (TNP 2198) in Participants With H. Pylori Infection

Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Rifasutenizol (TNP 2198) in Combination With Rabeprazole and Amoxicillin in the Primary Treatment of Participants With H. Pylori Infection

A multi-center, randomized, double-blind, bismuth-containing quadruple active comparator-controlled Phase 3 clinical study to evaluate the efficacy and safety of Rifasutenizol in combination with rabeprazole and amoxicillin in the primary treatment of participants with H. pylori infection using an adaptive design with sample size re-estimation.

Subjects will be randomly assigned to test group or control group at a 1:1 ratio stratified by study site, and will receive Rifasutenizol capsules, rabeprazole sodium enteric-coated tablets, amoxicillin capsules combined with clarithromycin placebo tablets and bismuth potassium citrate placebo capsules (test group), or bismuth-containing quadruple regimen of amoxicillin capsules, clarithromycin tablets, rabeprazole sodium enteric-coated tablets and bismuth potassium citrate capsules combined with RSZ placebo capsules (control group) for 14 consecutive days.

13C UBT will be performed 4 6 weeks after the last dose to evaluate the eradication effect of H. pylori.

Study Overview

• Status: Completed
• Conditions: H.Pylori Infection
• Intervention / Treatment: Drug: Rifasutenizol capsules; Drug: Rabeprazole sodium enteric-coated tablets; Drug: Amoxicillin Capsules; Drug: Clarithromycin placebo tablets; Drug: Bismuth potassium citrate placebo capsules; Drug: Clarithromycin tablets; Drug: Bismuth potassium citrate capsules; Drug: Rifasutenizol placebo capsules

• Study Type: Interventional
• Enrollment (Actual): 700
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: GuoZhu Geng, PhD, MD; Phone Number: +86-512-8686-1975; Email: guozhu.geng@tennorx.com
• Study Contact Backup: Name: Jing Chen; Email: jing.chen@tennorx.com

Study Locations

• China
  • Beijing, China
    • Peking University Third Hospital
    • Contact: Liya Zhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily sign the informed consent form.
• Age 18-65 years (inclusive), male or female.
• The result of 13C-UBT is positive (≥ 4 Delta Over Baseline), and the infection of H. pylori are confirmed by gastroscopic biopsy histology.
• Subjects agree to refrain from taking any antibiotics or traditional Chinese medicines with antibacterial effect, bismuth, and antacids (such as PPI, H2 receptor blocker, P-CAB) other than the study drugs during the Screening Period until the end of the study (Visit 5, i.e., Efficacy Evaluation Visit).
• Subjects and their heterosexual partners must agree to have no pregnancy plan and voluntarily take effective contraceptive measures during the trial and for at least 6 months after the end of the study medication.
• Willing to follow and able to complete all trial procedures.

Exclusion Criteria:

• Allergy to any of the study drugs (rabeprazole, amoxicillin, clarithromycin, bismuth potassium citrate), allergic constitution (multiple drug and food allergies); or any contraindication to the use of rifamycin, nitroimidazoles or study drugs.
• History of H. pylori eradication therapy (including participation in other clinical trials for H. pylori eradication).
• Subjects with confirmed tuberculosis (TB) or Mycobacterium avium complex (MAC) infection or a history of TB or MAC infection.
• History of dysphagia or any gastrointestinal disorder affecting drug absorption.
• History of obstruction pyloric; or excessive gastric acid secretion (such as Zollinger-Ellison syndrome).
• History of gastric cancer.
• History of neoplasm malignant within 5 years prior to screening, with the exception of basal cell carcinoma or carcinoma cervix in situ treated without evidence of recurrence.
• History of esophageal or gastric surgery, except for simple repair of the perforated ulcer.
• History of substance abuse or drug use within 5 years prior to screening.
• Alcohol abuse or a history of alcohol abuse within 5 years prior to screening (average weekly consumption of ≥ 14 units of alcohol: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine/Chinese rice wine/rice wine);
• Presence of active gastric and/or duodenal ulcer.
• Anticoagulant therapy or long-term treatment with nonsteroidal anti-inflammatory drugs.
• Treatment with any other investigational new drugs within 4 weeks prior to the Screening Period.
• Any prohibited medications or non-drug therapies as specified in the protocol (see Section 10.3).
• White blood cell count or neutrophil count below the lower limit of normal range.
• Anemia (hemoglobin < 90 g/L).
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, or serum creatinine above the upper limit of normal range.
• Test positive for hepatitis B surface antigen, hepatitis C antibody, AIDS antibody, or microspironema pallidum antibody.
• Abnormal ECG with clinical significance.
• Female subjects who are pregnant, lactating, or have a positive urine pregnancy result during the Screening Period.
• Inability to communicate with the Investigator and to comply with the study requirements.
• Other conditions considered inappropriate to participate in this study by the Investigator, e.g., the subject has a history of severe central nervous system, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrine, or hematological diseases, or has clinical manifestations of these diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group; Rifasutenizol capsules, 400 mg, BID, taken orally within half an hour after breakfast and dinner Rabeprazole sodium enteric-coated tablets, 20 mg, BID, taken orally within half an hour before breakfast and dinner Amoxicillin capsules, 1 g, BID, taken orally within half an hour after breakfast and dinner Clarithromycin placebo tablets, BID, taken orally within half an hour after breakfast and dinner Bismuth potassium citrate placebo capsules, BID, taken orally within half an hour before breakfast and dinner	Drug: Rifasutenizol capsules; 400 mg, BID; Other Names: TNP-2198 capsules; Drug: Rabeprazole sodium enteric-coated tablets; 20 mg, BID; Drug: Amoxicillin Capsules; 1 g, BID; Drug: Clarithromycin placebo tablets; BID; Drug: Bismuth potassium citrate placebo capsules; BID
Active Comparator: Control Group; Amoxicillin capsules, 1 g, BID, taken orally within half an hour after breakfast and dinner Clarithromycin tablets, 500 mg, BID, taken orally within half an hour after breakfast and dinner Rabeprazole sodium enteric-coated tablets, 20 mg, BID, taken orally within half an hour before breakfast and dinner Bismuth potassium citrate capsules, 240 mg, BID, taken orally within half an hour before breakfast and dinner Rifasutenizol placebo capsules, BID, taken orally within half an hour after breakfast and dinner	Drug: Rabeprazole sodium enteric-coated tablets; 20 mg, BID; Drug: Amoxicillin Capsules; 1 g, BID; Drug: Clarithromycin tablets; 500 mg, BID; Drug: Bismuth potassium citrate capsules; 240 mg, BID; Drug: Rifasutenizol placebo capsules; BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate of H.pylori Strain	The eradication rate of H. pylori (based on the test results of 13C UBT)	4 to 6 weeks after the last dose of the study drugs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate of Clarithromycin-resistant Strain of H.pylori	Percentage of Participants with Successful Helicobacter Pylori (H.pylori) Eradication in Participants with a Clarithromycin-resistant Strain of H.pylori at Baseline (based on the test results of 13C UBT)	4 to 6 weeks after the last dose of the study drugs

Collaborators and Investigators

• Sponsor: TenNor Therapeutics (Suzhou) Limited

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2023
• Primary Completion (Actual): March 26, 2024
• Study Completion (Actual): March 26, 2024

Study Registration Dates

• First Submitted: April 21, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Helicobacter Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Natriuretic Agents; Anti-Bacterial Agents; Diuretics; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Respiratory System Agents; Anticoagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Chelating Agents; Sequestering Agents; Expectorants; Calcium Chelating Agents; Antacids; Rabeprazole; Amoxicillin; Clarithromycin; Bismuth; Citric Acid; Sodium Citrate; Potassium Citrate
• Other Study ID Numbers: TNP-2198-07

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No