Trial Review

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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
28/02/2024
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-1C4610) 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 (30 participants) will only proceed if stage 1 (13 participants) is deemed successful.
Participants will be provided with 14 x 250ml bottles of the investigational medication. Participants will be clearly instructed to measure 60 mL of SVT-1C4610 into the measuring cup provided and consume immediately each morning and evening on an empty stomach and advised not to consume any food or drink for 30 minutes post dose. Each 60 mL dose of SVT-1C469 contains 1.9 x 10^12 (1.9 trillion) colony forming units (CFU) of bacterial species. They will be instructed to start consuming the SVT-1C469 at the clinic during Visit 1 and again that evening. The Participants are required to 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 28 days participants will return to the clinic with their participant diary. The participants will be provided a second diary for the following 28 days and they will continue to record any adverse events in the diary until their next visit.

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-1C4610 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 bacterial species present in SVT-1C4610, 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) Stage 1
(Day 0) Baseline, Day 28 (end of treatment), Day 56 (28 days post treatment) Stage 2
Primary outcome [2] 323180 0
To evaluate the efficacy of twice daily oral consumption of SVT-1C4610 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 for stage 1 and 28 days for stage 2
Timepoint [2] 323180 0
(Day 0) Baseline and Day 60 (30 days post treatment) stage 1
(Day 0) Baseline and Day 56 (28 days post treatment) stage 2
Secondary outcome [1] 381108 0
To evaluate the efficacy of SVT-1C4610 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) stage 1
(Day 0) Baseline, Day 28 (end of treatment), Day 56 (28 days post treatment) stage 2
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) stage 1
(Day 0) Baseline, Day 28 (end of treatment), Day 56 (28 days post treatment) stage 2

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
Sex
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 bacterial species, any component of SVT-1C4610 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-1C4610 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-1C4610 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
Completed
Date of first participant enrolment
Anticipated
5/10/2020
Actual
19/10/2020
Date of last participant enrolment
Anticipated
3/03/2024
Actual
30/10/2023
Date of last data collection
Anticipated
3/05/2024
Actual
28/11/2023
Sample size
Target
43
Accrual to date
Final
28
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
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
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
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
[email protected]
Contact person for public queries
Name 100775 0
Samantha Coulson
Address 100775 0
Servatus Ltd 12-14 Lomandra Place, COOLUM BEACH QLD, 4573
Country 100775 0
Australia
Phone 100775 0
+61 7 5357 6830
Fax 100775 0
Email 100775 0
[email protected]
Contact person for scientific queries
Name 100776 0
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
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.