Clinical trial NCT03198507: ERADICATE Hp2 - Treating Helicobacter Pylori With RHB-105 Compared to Active Comparator
Official title: A Randomized Double Blind Active Comparator Controlled Phase III Study to Assess the Safety and Efficacy of RHB-105 in the Treatment of Confirmed Helicobacter Pylori (H. Pylori) Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Helicobacter Pylori Infection
Dyspepsia
Lead sponsor: RedHill Biopharma Limited
Sponsor class: INDUSTRY
First posted: 2017-06-26
Enrollment: 455
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The "test and treat" strategy for treating dyspeptic patients who are H. pylori positive is rapidly becoming the standard of care. This study will test the effectiveness of RHB-105, a new triple therapy to treat H. pylori infection in dyspeptic patients against an active comparator.

Detailed description: This is a, randomized, double blind, active comparator-controlled study of RHB-105 in adult subjects complaining of epigastric discomfort that have been screened and found to be positive for H. pylori infection via 13C UBT and gastric biopsy.

The biopsy samples will also be used to conduct H. pylori antibiotic susceptibility/resistance assessment.

The study will be conducted at up to 65 sites in the USA. Eligible subjects will be randomized in a ratio of 1:1 between the RHB-105 arm (n=222) and the active comparator arm (n=222). Subjects will receive RHB-105 or active comparator for 14 consecutive days. Eradication of H. pylori infection will be determined at Visit 5 based on 13C UBT testing conducted between 43 and 71 days after initiation of study drug therapy.

All subjects who meet inclusion and exclusion criteria and have positive13C UBT will undergo upper endoscopy with sampling for culture and sensitivity testing (to rifabutin, amoxicillin, clarithromycin, and metronidazole) prior to randomization. After test of cure at Visit 5, all H. pylori eradication failures will receive susceptibility directed Standard of Care therapy based on initial culture results for subjects, and undergo repeat upper endoscopy for post treatment antibiotic susceptibility/resistance assessment.

Eligibility criteria: Inclusion Criteria:

1. Be ages 18 - 70, inclusive; non-Asian males and females (This population has been demonstrated to have significantly elevated omeprazole levels as per the prescriber information for other omeprazole products). A person having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent, including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam should be considered Asian, and forr this study Asian is defined as having at least one Asian grandparent (Shektar et al, 2014, FDA Guidance for Industry 2016);
2. Positive for H. pylori by 13C Urea Breath Test (UBT) and confirmed positive via gastric biopsy for campylobacter-like organism (CLO) Rapid Urease Test, or H. pylori culture or histology;
3. Symptoms consistent with dyspepsia of at least two weeks duration (defined as recurrent pain or discomfort centered in the upper abdomen, often with a relation to meals);
4. Females must not be pregnant or lactating and:

   1. at no risk of pregnancy for one of the following reasons: postmenopausal for at least one year from the date of informed consent, status post hysterectomy or tubal ligation, OR
   2. are prepared to and agree to use of an intrauterine device (IUD) or practice double method birth control (barrier plus spermicide) from screening through to 30 days post-end of-treatment (EOT); Acceptable double contraceptive methods include barrier (condoms or diaphragms) plus spermicide
   3. Hormonal contraceptives (birth control pills and hormone implants) are not acceptable contraception methods under this protocol;
5. Males must be surgically sterilized or are prepared to and agree to practice double method (barrier plus spermicide) birth control from screening through to 30 days post-EOT;
6. Agree to refrain from consuming alcohol from 1 week prior to screening to Test of Cure/Visit 5;
7. Agree to refrain from taking antacids from screening through day 15 and for at least 24 hours prior to Test of Cure/Visit 5 and if applicable at least 24 hours prior to Visit 8/Test of Cure;
8. Agree to refrain from taking H2 blockers at least 24 hours prior to screening 13C UBT and at least 24 hours prior to Test of Cure/Visit 5 and if applicable at least 24 hours prior to Visit 8/Test of Cure;
9. Agree to refrain from taking sucralfate from one week prior to screening through Test of Cure/Visit5;
10. Agree to refrain from taking bismuth containing medications such as Pepto-BismolTM or other proton pump inhibitors (PPIs) from two weeks prior to screening through Test of Cure/Visit 5;
11. Agrees to refrain from consuming grapefruit, or any other food or supplement known to significantly affect CYP3A4 or CYP2C19 activity from screening to day 15;
12. Provide written informed consent to participate as shown by a signature of subject on the consent form.

Exclusion Criteria:

1. Have alarm symptoms/signs (including unexplained anemia \[iron deficiency\], melena / hematemesis, anorexia, dysphagia, jaundice, weight loss);
2. Have received prior H. pylori eradication therapy;
3. Use of antibiotics in the 4 weeks immediately prior to screening 13C UBT;
4. Use of any proton pump inhibitors (PPIs) or bismuth-containing medications (such as Pepto-BismolTM) within the 2 weeks immediately prior to screening 13C UBT;
5. Use of any of the following medications within seven days prior screening: alfentanil, allopurinol, amlodipine, anti-herpes agents, anti-retroviral agents, apixaban, aprepitant, aripiprazole, astemizole, atorvastatin, boceprevir, buspirone, carbamazepine, cisapride, citalopram dosed greater than 20 mg /d, clomipramine, clopidogrel and other oral anticoagulants, colchicine, dapsone, dihydroergotamine, digoxin, diltiazem, ergotamine, felodipine, fluconazole, gleevec, hormonal contraceptives that are not exclusively norethindrone or norgestrel, imipramine, itraconazole, ketoconazole, latuda, lovastatin, mycophenolate mofetil, nifedipine, nisoldipine, nitrendipine, phenytoin, pimozide, probenecid, proguanil, quinine, roflumilast, terfenadine and voriconazole;
6. Use of amiodarone;
7. Presence of more than two active gastric and/or duodenal ulcers;
8. History of gastric outlet obstruction; or hypersecretory state (e.g., Zollinger Ellison Syndrome);
9. History of esophageal or gastric surgery, except for simple closure of perforated ulcer;
10. History of gastric cancer;
11. History of malignancy within the past five years except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been treated with no evidence of recurrence;
12. Positive screening laboratory results for human immunodeficiency virus (HIV) antibody (HIV1 or HIV2), or hepatitis B surface antigen (HBs Ag), or hepatitis C antibody (HCV Ab), unless patient has documented sustained viral response evidenced by prior and/or current absence of viral RNA at least 24 weeks after completing antiviral therapy;
13. Current drug or alcohol abuse or history of drug or alcohol abuse in the past 5 years from screening;
14. Known hypersensitivity or suspected history of hypersensitivity reactions to any of the study drugs or related drugs, including cephalosporins and penicillin;
15. Clinical evidence of any disease that in the opinion of the investigator might interfere with the subject's ability to participate in the trial;
16. History of QT prolongation (QTc greater than 450ms in males and 460ms in females), or ventricular arrhythmia, including torsades de pointes;
17. Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) \>3x Upper Limit of Normal (ULN), or Alkaline Phosphatase (APO4) \>2x ULN, or Total Bilirubin \>2x ULN. Subjects with confirmed diagnosis of Gilbert's Syndrome are excluded if Total Bilirubin \> 2.5x ULN;
18. Unable to communicate well with the Investigators and to comply with the study requirements;
19. Involved in any other experimental drug or device protocol (outside of this RHB-105-02 study) within the 4 weeks immediately prior to screening visit through end of study;
20. Subjects with creatinine clearance less than 30 ml/min at screening via estimated Cockcroft-Gault (eCGF) formula: eCGF or estimated creatinine clearance = \[140 - age in years\] \* weight (kg) / 72 \* Serum Creatinine (mg/dl) \[multiply estimated rate by 0.85 for women\], using actual body weight at screening.

Primary outcomes:
measure: Number of Participants With Eradication of H. Pylori
timeFrame: 43-71 days after initiation of treatment
Secondary outcomes:
measure: Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
timeFrame: 43-71 days after initiation of treatment
measure: Number of Participants With Adverse Events That Are Related to Treatment
timeFrame: After first dose of study drug until 28 days following last dose.
Other outcomes:
measure: Number of Participants With Eradication of H. Pylori in the Pharmacokinetic Population (PKP)
timeFrame: 43-71 days after initiation of treatment
Locations:
city: Dothan
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: North Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Anaheim
country: United States
facility: Research Site
state: California
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Lomita
country: United States
facility: Research Site
state: California
city: San Carlos
country: United States
facility: Research site
state: California
city: Bristol
country: United States
facility: Research Site
state: Connecticut
city: Aventura
country: United States
facility: Research Site
state: Florida
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Coral Springs
country: United States
facility: Research Site
state: Florida
city: Homestead
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Lauderdale Lakes
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orange City
country: United States
facility: Research Site
state: Florida
city: Palm Harbor
country: United States
facility: Research Site
state: Florida
city: Athens
country: United States
facility: Research Site
state: Georgia
city: Macon
country: United States
facility: Research Site
state: Georgia
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Elwood
country: United States
facility: Research Site
state: Indiana
city: Metairie
country: United States
facility: Research Site
state: Louisiana
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Chevy Chase
country: United States
facility: Research Site
state: Maryland
city: Brockton
country: United States
facility: Research Site
state: Massachusetts
city: Chesterfield
country: United States
facility: Research Site
state: Missouri
city: Wyoming
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Great Neck
country: United States
facility: Research Site
state: New York
city: Concord
country: United States
facility: Research Site
state: North Carolina
city: Davidson
country: United States
facility: Research Site
state: North Carolina
city: Fayetteville
country: United States
facility: Research Site
state: North Carolina
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Tulsa
country: United States
facility: Research Site
state: Oklahoma
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Sioux Falls
country: United States
facility: Research Site
state: South Dakota
city: Hermitage
country: United States
facility: Research site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Center
state: Texas
city: Houston
country: United States
facility: Research site
state: Texas
city: Longview
country: United States
facility: Research Site
state: Texas
city: Richardson
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Ogden
country: United States
facility: Research Site
state: Utah
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Christiansburg
country: United States
facility: Research Site
state: Virginia
city: Lynchburg
country: United States
facility: Research Site
state: Virginia
city: Milwaukee
country: United States
facility: Research site
state: Wisconsin
Study officials:
affiliation: Baylor College of Medicine
name: David Graham, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Howden CW, Sheldon KL, Almenoff JS, Chey WD. Pitfalls of Physician-Directed Treatment of Helicobacter pylori: Results from Two Phase 3 Clinical Trials and Real-World Prescribing Data. Dig Dis Sci. 2022 Sep;67(9):4382-4386. doi: 10.1007/s10620-021-07323-5. Epub 2021 Dec 4.
citation: Graham DY, Canaan Y, Maher J, Wiener G, Hulten KG, Kalfus IN. Rifabutin-Based Triple Therapy (RHB-105) for Helicobacter pylori Eradication: A Double-Blind, Randomized, Controlled Trial. Ann Intern Med. 2020 Jun 16;172(12):795-802. doi: 10.7326/M19-3734. Epub 2020 May 5.