Trial Outcomes & Findings for ERADICATE Hp2 - Treating Helicobacter Pylori With RHB-105 Compared to Active Comparator (NCT NCT03198507)

NCT ID: NCT03198507

Last Updated: 2020-03-16

Results Overview

Eradication of H. pylori confirmed via 13C Urea Breath Test (UBT) testing. Subjects with negative test results (eradication of H. pylori) were considered treatment successes. Subjects who tested positive for H. pylori infection (no eradication) were considered treatment failures.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

455 participants

Primary outcome timeframe

43-71 days after initiation of treatment

Results posted on

2020-03-16

Participant Flow

This study was conducted between July 2017 and December 2018. A total of 62 centers in the US screened potential subjects and 55 centers randomized subjects into the study.

Participant milestones

Participant milestones
Measure
RHB-105
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Overall Study
STARTED
228
227
Overall Study
COMPLETED
227
227
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
RHB-105
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Overall Study
Withdrawal by Subject
1
0

Baseline Characteristics

ERADICATE Hp2 - Treating Helicobacter Pylori With RHB-105 Compared to Active Comparator

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
RHB-105
n=228 Participants
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
n=227 Participants
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Total
n=455 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
214 Participants
n=5 Participants
207 Participants
n=7 Participants
421 Participants
n=5 Participants
Age, Categorical
>=65 years
14 Participants
n=5 Participants
20 Participants
n=7 Participants
34 Participants
n=5 Participants
Age, Continuous
45.9 years
STANDARD_DEVIATION 12.77 • n=5 Participants
47.2 years
STANDARD_DEVIATION 13.13 • n=7 Participants
46.5 years
STANDARD_DEVIATION 12.95 • n=5 Participants
Sex: Female, Male
Female
132 Participants
n=5 Participants
151 Participants
n=7 Participants
283 Participants
n=5 Participants
Sex: Female, Male
Male
96 Participants
n=5 Participants
76 Participants
n=7 Participants
172 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
149 Participants
n=5 Participants
124 Participants
n=7 Participants
273 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
79 Participants
n=5 Participants
103 Participants
n=7 Participants
182 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
0 Participants
n=5 Participants
3 Participants
n=7 Participants
3 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Black or African American
35 Participants
n=5 Participants
53 Participants
n=7 Participants
88 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Native Hawaiian or Other Pacific Islander
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · White
184 Participants
n=5 Participants
167 Participants
n=7 Participants
351 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Other
7 Participants
n=5 Participants
4 Participants
n=7 Participants
11 Participants
n=5 Participants
Region of Enrollment
United States
228 participants
n=5 Participants
227 participants
n=7 Participants
455 participants
n=5 Participants
BMI
30.32 Kg/m^2
STANDARD_DEVIATION 6.027 • n=5 Participants
30.95 Kg/m^2
STANDARD_DEVIATION 6.886 • n=7 Participants
30.63 Kg/m^2
STANDARD_DEVIATION 6.470 • n=5 Participants

PRIMARY outcome

Timeframe: 43-71 days after initiation of treatment

Population: Full Analysis Set (FAS)

Eradication of H. pylori confirmed via 13C Urea Breath Test (UBT) testing. Subjects with negative test results (eradication of H. pylori) were considered treatment successes. Subjects who tested positive for H. pylori infection (no eradication) were considered treatment failures.

Outcome measures

Outcome measures
Measure
RHB-105
n=228 Participants
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
n=227 Participants
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Number of Participants With Eradication of H. Pylori
191 Participants
131 Participants

SECONDARY outcome

Timeframe: 43-71 days after initiation of treatment

Population: n is the number of cultures obtained from the in the FAS population in each treatment group with H. pylori resistant/susceptible to Rifabutin, Amoxicillin, Clarithromycin or Metronidazole at baseline

The primary endpoint was summarized within subgroups formed by the presence of H. pylori susceptibility and resistance to amoxicillin, clarithromycin, metronidazole, and rifabutin from H. pylori cultures from samples obtained prior to initiating study treatment (i.e. baseline). A participant is considered a responder when H. pylori is eradicated after treatment as confirmed via 13C Urea Breath Test (UBT). A participant is considered a non-responder when H. pylori is not eradicated after treatment.

Outcome measures

Outcome measures
Measure
RHB-105
n=174 Participants
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
n=171 Participants
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Rifabutin Susceptible · Non-responder
27 Participants
72 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Rifabutin resistant · Responder
0 Participants
0 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Rifabutin resistant · Non-responder
0 Participants
0 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Rifabutin Susceptible · Responder
147 Participants
99 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Amoxicillin Resistant · Responder
9 Participants
4 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Amoxicillin Resistant · Non-responder
4 Participants
5 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Amoxicillin Susceptible · Responder
138 Participants
95 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Amoxicillin Susceptible · Non-responder
23 Participants
67 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Clarithromycin Resistant · Responder
21 Participants
22 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Clarithromycin Resistant · Non-responder
4 Participants
13 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Clarithromycin Susceptible · Responder
126 Participants
77 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Clarithromycin Susceptible · Non-responder
23 Participants
59 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Metronidazole Resistant · Responder
57 Participants
45 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Metronidazole Resistant · Non-responder
14 Participants
34 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Metronidazole Susceptible · Responder
90 Participants
53 Participants
Number of Participants With H. Pylori Cultures That Presented Antibiotic Resistance and Susceptibility
Metronidazole Susceptible · Non-responder
13 Participants
38 Participants

SECONDARY outcome

Timeframe: After first dose of study drug until 28 days following last dose.

Population: Safety Population

The number of participants that presented treatment emergent adverse events (TEAE) during the study overall, TEAEs related to study drug and severe TEAEs.

Outcome measures

Outcome measures
Measure
RHB-105
n=228 Participants
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
n=227 Participants
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Number of Participants With Adverse Events That Are Related to Treatment
No. of subjects with any TEAE
83 Participants
72 Participants
Number of Participants With Adverse Events That Are Related to Treatment
No. of subjects with any study drug related TEAE
47 Participants
44 Participants
Number of Participants With Adverse Events That Are Related to Treatment
No. of subjects with any severe TEAE
4 Participants
4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 43-71 days after initiation of treatment

Population: Pharmacokinetic Population (PKP)

A pre-specified responder analysis of eradication of H. pylori confirmed via 13C Urea Breath Test (UBT) was performed in the PK population. The PK population was generated based on the measurement of plasma concentrations of amoxicillin, omeprazole, rifabutin, and the rifabutin metabolite 25-O-desacetyl-rifabutin (on Day 13). It included those subjects in the FAS who had demonstrable presence of any component of investigational drug at Visit 3 or had no levels detected \>250 hours after the last dose. For all subjects, the reason for exclusion from the PKP was the absence of any pharmacokinetic component of study drug at Visit 3 within 250 hours of the last reported dose. Two hundred fifty hours was selected to account for approximately 10 times the terminal half-life of rifabutin.

Outcome measures

Outcome measures
Measure
RHB-105
n=207 Participants
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
n=184 Participants
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Number of Participants With Eradication of H. Pylori in the Pharmacokinetic Population (PKP)
187 Participants
119 Participants

Adverse Events

RHB-105

Serious events: 1 serious events
Other events: 51 other events
Deaths: 0 deaths

Active Comparator

Serious events: 1 serious events
Other events: 46 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
RHB-105
n=228 participants at risk
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
n=227 participants at risk
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Metabolism and nutrition disorders
Diabetic ketoacidosis
0.44%
1/228 • Number of events 1 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.
0.00%
0/227 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.
Nervous system disorders
Acute Encephalopathy
0.00%
0/228 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.
0.44%
1/227 • Number of events 1 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.

Other adverse events

Other adverse events
Measure
RHB-105
n=228 participants at risk
RHB-105 (Rifabutin 150 mg, Amoxicillin 3000 mg, Omeprazole 120 mg)
Active Comparator
n=227 participants at risk
Active comparator (Amoxicillin 3000 mg, Omeprazole 120 mg)
Gastrointestinal disorders
Diarrhoea
10.1%
23/228 • Number of events 23 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.
7.9%
18/227 • Number of events 18 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.
Gastrointestinal disorders
Nausea
4.8%
11/228 • Number of events 11 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.
5.3%
12/227 • Number of events 12 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.
Nervous system disorders
Headache
7.5%
17/228 • Number of events 17 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.
7.0%
16/227 • Number of events 16 • Adverse Events and Serious Adverse Events reported from first study drug administration and until 28 days following the last dose of blinded study drug.

Additional Information

June Almenoff, Chief Scientific Officer

Redhill Biopharma Inc.

Phone: (984) 444 7010

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60