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Trial registered on ANZCTR


Registration number
ACTRN12620000923965
Ethics application status
Approved
Date submitted
26/06/2020
Date registered
17/09/2020
Date last updated
17/09/2020
Date data sharing statement initially provided
17/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Testing safety and efficacy of a live bacterial therapy for the treatment of Helicobacter pylori infection
Scientific title
A two-stage phase I study to assess safety and efficacy of a live microbial biotherapeutic (SVT-1C469) as monotherapy for the treatment of Helicobacter pylori infection in otherwise healthy adults.
Secondary ID [1] 300750 0
None
Universal Trial Number (UTN)
U1111-1247-7832
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Helicobacter pylori infection 316597 0
Condition category
Condition code
Infection 314824 314824 0 0
Other infectious diseases
Oral and Gastrointestinal 314825 314825 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a two stage - phase 1 study. Stage 2 will only proceed if stage 1 (13 participants) is deemed successful and will be run identical to Stage 1 with the exception of participant numbers (Stage 2 - 30 participants). Participants will be provided with 4 x 250ml bottle of the investigational medication. Participants will carefully measure out 15mls and orally consume 15 mLs of undiluted investigational bacterial monotherapy, SVT-1C469, twice daily for 30 days. Each 15 mL dose of SVT-1C469 contains 1.5 x 10^12 (1.5 trillion) colony forming units (CFU) of Lactobacillus bacterial species. 15 mls of undiluted solution will be consumed in the morning and evening with food, with the participants required to record each dose taken. Participants will record their adherence to the intervention in a participant diary, along with any adverse events and any concomitant medications taken during the study period. At the end of the 30 days participants will return the participant diary and medication bottles to the study co-ordinator to account for missed doses, if any. The participants will be provided a second diary for the following 30 days and they will continue to record any adverse events in the diary following the study period.

Stage 2 will only proceed if there are no serious adverse events reported and the principal investigator deems it safe to do so, and at least 3 of the 13 participants are responders. A responder is defined as a participant that has a reduction in their urea breath test of greater than or equal to 38% on day 60 compared to baseline.
Intervention code [1] 317082 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323179 0
To evaluate the safety of twice daily oral consumption of SVT-1C469 in adult participants identified as positive for Helicobacter pylori (H. pylori) infection, but who are otherwise healthy. The same assessments apply to both stage 1 and stage 2 of the study.
Assessed on systemic tolerability based on vital signs,
- Blood Pressure and Heart Rate measured by using a sphygmomanometer,
- Temperature measured with a thermometer
- Respiratory rate counted by the Investigator based on number of times the chest rises in 1 minute with participant in Supine position.
Assessed by incidence of treatment emergent adverse events (TEAEs) and discontinuations due to adverse events (AEs) determined from participant diaries;
And laboratory abnormalities assessed by blood haematological (complete blood count with ESR) and biochemical (electrolytes, creatinine, alkaline phosphates, albumin and C-RP) parameters and urinalysis (pH, protein, glucose, ketone, blood and microscopic sediment]
Examples of known/possible adverse reactions/events:
Human safety and efficacy studies have not yet been conducted with the specific combination of Lactobacillus bacteria present in SVT-1C469, however their individual safety for human consumption is well recognised and documented. Each species has a Risk Group 1 Classification in that they are not associated with disease in healthy adults and all have been granted the Qualified Presumption of Safety (QPS) status by the European Food Safety Authority (EFSA).
Potential adverse events that participants may experience include mild gastrointestinal symptoms including abdominal discomfort, bloating, flatulence and/or nausea.
Timepoint [1] 323179 0
(Day 0) Baseline, Day 30 (end of treatment), Day 60 (30 days post treatment)
Primary outcome [2] 323180 0
To evaluate the efficacy of twice daily oral consumption of SVT-1C469 in adult participants identified as positive for H. pylori infection, but who are otherwise healthy. The same assessments apply to both stage 1 and stage 2 of the study.
Efficacy of the intervention will be assessed by determining the presence/absence of Helicobacter pylori infection using a urea breath test (UBT) 30 days after the end of treatment compared to baseline value and response based will be based on a increase/decrease of the UBT value 30 days after the end of treatment compared to baseline.

Timepoint [2] 323180 0
(Day 0) Baseline and Day 60 (30 days post treatment)
Secondary outcome [1] 381108 0
To evaluate the efficacy of SVT-1C469 in reducing gastrointestinal symptoms associated with H. pylori infection. The same assessments apply to both stage 1 and stage 2 of the study.

Change in gastrointestinal symptoms associated with H. pylori infection will be assessed using the Structured Assessment of Gastrointestinal Symptom Scale (SAGIS score).
Timepoint [1] 381108 0
(Day 0) Baseline, Day 30 (end of treatment), Day 60 (30 days post treatment)
Secondary outcome [2] 381303 0
To evaluate the difference in efficacy between patients who have undergone prior treatment for H. pylori and those without any prior treatment. The same assessments apply to both stage 1 and stage 2 of the study.
Efficacy of the intervention will be assessed by determining the presence/absence of Helicobacter pylori infection using a urea breath test (UBT) and response based will be based on a increase/decrease of the UBT value.
Timepoint [2] 381303 0
(Day 0) Baseline, Day 30 (end of treatment), Day 60 (30 days post treatment)
Secondary outcome [3] 386018 0
To evaluate the efficacy of SVT-1C469 in reducing gastrointestinal symptoms associated with H. pylori infection. The same assessments apply to both stage 1 and stage 2 of the study.

Change in gastrointestinal symptoms associated with H. pylori infection will be assessed using the Rome III criteria
Timepoint [3] 386018 0
(Day 0) Baseline, Day 30 (end of treatment), Day 60 (30 days post treatment)

Eligibility
Key inclusion criteria
- Male and female participants aged 18 years or older, capable of providing own informed consent and able to attend the Princess Alexandra Hospital as required for study visits;
- Determined by medical history and clinical judgement of the investigator to be medically healthy;
- Females of childbearing potential (FOCBP) must have a negative pregnancy test at baseline;
- Females (FOCBP) and males must use contraception while on the study;
-Positive for H. pylori infection at screening confirmed by a positive urea breath test;

Able to adhere to the medication guidelines prior to undertaking the urea breath test (if applicable) that includes:
-No antibiotics or bismuth containing medication (Nexium, Klacid, Pepto-Bismol) use 4 weeks prior to the test;
-No acid suppressant medications (Losec, Somac, Nexium, Pariet) use 7 days prior to the test (can be resumed after testing if required);
-No short-term acid suppressant medications (Zantac, Nizatidine, Mylanta, Rennies) within 48 hours prior to the test (can be resumed after testing if required).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Immunocompromised Participants, or those with known or suspected history of immunodeficiency, as determined by medical history review, physical examination and/or laboratory findings;
-History of severe adverse reaction including but not limited to anaphylaxis (or a suspicion of this by the Investigator) to any products containing Lactobacillus species, any component of SVT-1C469 or any antibiotic commonly used to treat bacterial infections;
-Any history of anti–tumour necrosis factor (TNF) treatment or other Immunosuppressant medications;
-Current use of corticosteroids: equal to or greater than 15mg/daily of oral prednisolone daily (or equivalent) and/or history of intermittent corticosteroids usage equal to or greater 40mg/daily of oral prednisolone (or equivalent) of >3 days in the last 3 months;
-Use of antibiotics within 4 weeks of the Baseline Visit (Day 0) and for the study duration;
-Females who are pregnant or breastfeeding or planning on becoming pregnant for the study period (treatment and follow-up periods);
-Any condition that, in the opinion of the Investigator, contraindicates participation in this study or poses an additional risk to the Participant including any known and/or suspected medical or psychiatric conditions, history of active peptic ulcer disease and/or gastroesophageal disease, severe gastritis or presence of alarm symptoms.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
This is a two-stage Phase I clinical trial design. Stage I is to first ascertain if SVT-1C469 is well tolerated and effective in eradicating H. pylori infection as an open-label, single group design in an otherwise healthy adult population. Stage I will recruit 13 participants. At the completion of the first stage, an interim analysis will be conducted to determine if the second stage should be conducted. If the number of Participants responding is greater than 3 in Stage I, then the second stage will be conducted. Otherwise, it will not. Stage II will further assess the safety and efficacy of SVT-1C469 in eradicating H. pylori infection in a further 30 Participants in an open-label, single group design in an otherwise healthy adult population using the same outcome measures and assessments as Stage I.
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Response rates are specified as assumed under the null hypothesis (H0), p1, and a minimum important effect size resulting in a response rate under the alternate hypothesis, p2. The proposed sample size has been calculated using the method described by Englert & Kieser (2012) and selecting the sample sizes for the optimal design. Statistical power has been set at 0.8 and statistical significance level at 0.05 (two-tailed). Assuming p1 equals 0.2 (20%) and p2 equals 0.4 (40%), thirteen individuals will be recruited in stage 1 and the study will proceed to stage 2 if there are three responders. A total sample of forty-three individuals will be recruited across stages 1 and 2. The appropriateness of p1 and p2 need to be confirmed with clinical experts.

The results from stage 1 will, in themselves, only be used to determine progression to stage 2, if greater than or equal to 3 participants are responders, or not if less than 3. The combined results from stages 1 and 2 will be used to test the statistical null hypothesis that the response rate is less than or equals 0.2 (20%). Hypothesis tests and 95% confidence intervals will be as described in Kieser et al (2017) which allows for the potential bias in simple inference of proportions caused by the potential to not follow through to stage 2 in this design.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 16103 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 29618 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 305207 0
Commercial sector/Industry
Name [1] 305207 0
Servatus Ltd
Address [1] 305207 0
Servatus Ltd
12-14 Lomandra Place
Coolum Beach
Qld, 4573
Country [1] 305207 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Servatus Ltd
Address
Servatus Ltd
12-14 Lomandra Place
Coolum Beach
Qld, 4573
Country
Australia
Secondary sponsor category [1] 305565 0
None
Name [1] 305565 0
Address [1] 305565 0
Country [1] 305565 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305558 0
Metro South Health Human Research Ethics
Ethics committee address [1] 305558 0
Metro South Health HREC
Metro South Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 305558 0
Australia
Date submitted for ethics approval [1] 305558 0
17/03/2020
Approval date [1] 305558 0
24/06/2020
Ethics approval number [1] 305558 0
HREC/2020/QMS/62543

Summary
Brief summary
The aim of this study is to evaluate safety and efficacy of SVT-1C469 as a monotherapy treatment for eradicating H. pylori infection. The treatment consists of carefully selected Lactobacillus bacteria that have demonstrated bactericidal activity against H. pylori in vitro. Lactobacillus bacteria are part of a healthy gut microbiome, including the stomach. An altered balance of bacteria in the gut, including decreased Lactobacillus is observed in people with H. pylori infection. When H. pylori is eradicate from the stomach, the gastric microbiota is observed to rebalance to a more healthy state. Proposed mechanisms for Lactobacillus species in eradicating H. pylori infection include competition for adhesion sites on the gastric epithelium, improved gastric mucosal barrier function, production of antimicrobial peptides against H. pylori, down regulation of inflammatory cytokines that are induced by H. pylori and by Lactobacillus binding to H. pylori forming complexes that can be removed from the stomach via the gastrointestinal tract. There is evidence that monotherapy with high doses of beneficial bacteria is successful in eradicating H. pylori in a certain number of cases and several studies have found a greater response to eradicating H. pylori when standard treatment is given together with beneficial bacteria. This study will help determine how effective a high dose of SVT-1C469 is as a stand-alone therapy in eradicating H. pylori and reducing symptoms.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100774 0
Prof Gerald Holtmann
Address 100774 0
Department of Gastroenterology & Hepatology,
Princess Alexandra Hospital
199 Ipswich Road,
WOOLLOONGABBA,
QLD, 4102
Country 100774 0
Australia
Phone 100774 0
+61 731767792
Fax 100774 0
Email 100774 0
gerald.holtmann@health.qld.gov.au
Contact person for public queries
Name 100775 0
Dr Natasha Koloski
Address 100775 0
Department of Gastroenterology & Hepatology,
Princess Alexandra Hospital
199 Ipswich Road
WOOLLOONGABBA
QLD, 4102
Country 100775 0
Australia
Phone 100775 0
+61 7 3176 9091
Fax 100775 0
Email 100775 0
n.koloski@uq.edu.au
Contact person for scientific queries
Name 100776 0
Dr Samantha Coulson
Address 100776 0
Servatus Ltd
12-14 Lomandra Place
COOLUM BEACH
QLD, 4573
Country 100776 0
Australia
Phone 100776 0
+61 7 5357 6830
Fax 100776 0
Email 100776 0
samantha.coulson@servatus.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be made available as the investigational treatment will be patent pending.
What supporting documents are/will be available?
No other documents available
Summary results
No Results