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Trial registered on ANZCTR


Registration number
ACTRN12621001657819
Ethics application status
Approved
Date submitted
5/11/2021
Date registered
1/12/2021
Date last updated
30/08/2024
Date data sharing statement initially provided
1/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Testing safety and efficacy of a live bacterial therapy for the treatment of active Rheumatoid Arthritis.
Scientific title
A Randomised, Double-Blind, Placebo-Controlled, Parallel Dose Comparison Study Evaluating Safety and Efficacy of SVT-6A4710 in Adults with active Rheumatoid Arthritis.
Secondary ID [1] 305419 0
None
Universal Trial Number (UTN)
U1111-1269-9232
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis (RA) 323786 0
Rheumatoid Factor Positive (Seropositive) 323788 0
Rheumatoid Factor Negative (Seronegative) 323789 0
Condition category
Condition code
Inflammatory and Immune System 321300 321300 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study duration consists of a total of 16 weeks consisting of 12 weeks of intervention (treatment) and an additional 4 weeks as an observation period (no treatment). Participants will be provided with 21 x 250 mL bottles in total containing the investigational medicine(s), or placebo. Participants will take 25 mL of SVT-6A4710 oral liquid or placebo oral liquid twice daily for 12 weeks.
Dose 1 of SVT-6A4710 contains 1.5 x 10^9 colony forming units (CFU) of bacterial species (1.5 Billion CFU per 25 mL dose). Dose 2 of SVT-6A4710 contains 1.5 x 10^11 CFU of bacterial species (150 Billion per 25 mL dose). Placebo will contain inactive ingredients only.
Participants are required to record each dose taken. Participants will record their adherence to the intervention in a participant diary, any adverse events and any concomitant medications taken during the study period.
Intervention code [1] 321822 0
Treatment: Drugs
Comparator / control treatment
The treatment medications Dose 1, Dose 2, and Placebo are randomised in a 1:1:1 ratio. The Placebo is a medication that contains no active ingredients or has medical benefit. It contains the same ingredients as the treatment with no bacteria. It will look, taste and smell the same as the treatment drugs. Participants will receive 21 bottles in total throughout the study treatment duration, each with 250 mL of oral liquid. Participants will consume 25 mL of investigational product twice daily.
Control group
Placebo

Outcomes
Primary outcome [1] 329082 0
To assess the efficacy in response to twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis. Efficacy of intervention assessed by achieving a Clinical Disease Activity Index (CDAI) low disease activity score of equal to or less than 10.
Timepoint [1] 329082 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [1] 402686 0
To assess ACR20 response rates with twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis. Efficacy of intervention assessed by a validated measure to compare improvement of Rheumatic symptoms. It is a composite measure defined as both improvement of 20 percent in the number of tender and number of swollen joints, and a 20 percent improvement in three of the following five criteria: patient and physician global assessments, Health Assessment Questionnaire - Disability Index (HAQ-DI), visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Timepoint [1] 402686 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [2] 402687 0
To assess change to Disease Activity Score (DAS) at 28 joints with erythrocyte sedimentation rate in response to twice daily oral consumption of SVT-6A479 in adult participants confirmed to have active Rheumatoid Arthritis. Efficacy of intervention assessed by a composite score of 4 measures; tender and swollen joint counts (28 joints assessed), erythrocyte sedimentation rate or CRP.
Timepoint [2] 402687 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [3] 402688 0
To assess change to Participant Assessment of Pain Score in response to twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis . Efficacy of intervention assessed by a single visual scale marking from 0 (no pain) to 100 (most severe pain) indicating level of pain.
Timepoint [3] 402688 0
Day 0 (baseline), Weeks 4,8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [4] 402689 0
To assess proportion achieving ACR50 or ACR70 response rates with twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis. Efficacy of intervention assessed by a validated measure to compare improvement of Rheumatic symptoms. It is a composite measure defined as both improvement of 50/ 70 percent in the number of tender and number swollen joints, and a 50/ 70 percent improvement in three of the following criteria: patient and physician global assessments, Health Assessment Questionnaire - Disability Index, visual analogue pain scale, and erythrocyte sedimentation rate to C-reactive protein (CRP).
Timepoint [4] 402689 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [5] 402690 0
To assess achieved CDAI remission score of less than or equal to 2.8 in response to twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis. Efficacy of intervention assessed by the sum of 4 outcome parameters using tender and swollen joint counts (28 joints assessed) and patient's and physicians’ global assessments of disease activity.
Timepoint [5] 402690 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [6] 402691 0
To assess change in Health Assessment Questionnaire Disability Index scores (HAQ-DI) in response to twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis. Efficacy of intervention assessed by degree of difficulty on 8 parameters of daily living activities.
Timepoint [6] 402691 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [7] 402692 0
To assess change in Functional Assessment of Chronic Illness Therapy (FACIT) scores in response to twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis. Efficacy of intervention assessed by measuring level of fatigue during daily activities over the past week.
Timepoint [7] 402692 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [8] 402693 0
To assess safety in response to twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis. Assessed by incidence of treatment emergent adverse events (TEAEs) and discontinuations due to adverse events (AEs) - determined from participant diaries and systemic vital sign tolerability: - 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. Examples of known/possible adverse reactions/events: Human safety and efficacy studies have not yet been conducted with the specific combination of bacteria species present in SVT-6A4710, 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), headache and/or drowsiness.
Timepoint [8] 402693 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).
Secondary outcome [9] 402694 0
To assess safety in response to twice daily oral consumption of SVT-6A4710 in adult participants confirmed to have active Rheumatoid Arthritis. Safety of intervention assessed as a composite outcome with blood haematological, biochemical, liver enzyme parameters and urinalysis.
Timepoint [9] 402694 0
Day 0 (baseline), Weeks 4, 8, 12 (end of treatment) and 16 (follow-up).

Eligibility
Key inclusion criteria
1. Male and female Participants aged 18 to 80 years, capable of providing verbal informed consent and able to attend the clinic as required for the study;
2. Participants must have active Rheumatoid Arthritis meeting classification criteria according to the 2010 ACR/EULAR guidelines with a score equal to or greater than 6/10;
3. Participants must have a Clinical Disease Activity Index (CDAI) Score greater than 10;
4. Participants may or may not be taking conventional DMARD therapies;
5. If taking DMARD therapy, they must have been taking it continuously for at least 3 months prior to the first dose of study drug and be on a stable weekly dose for at least 4 weeks prior to the first dose of study drug and be maintained for the study duration, as:
a. Sulfasalazine less than or equal to 2000 mg/day
b. Hydroxychloroquine less than or equal to 200 mg/day
c. Leflunomide less than or equal to 20 mg/day
d. Azathioprine less than or equal to 4 mg/kg per day
e. Methotrexate less than or equal to 25 mg/week
6. If taking low dose prednisone, they must be taking it continuously for 3 months and be on a stable dose of less than 7.7 mg/day for 4 weeks prior to the first dose of the study drug. Tapering or removing prednisone from treatment plan will be based on disease activity assessed at each clinic visit;
7. Must have normal differential white cell counts within reference range at screening:
a. Lymphocytes (1.1 - 4.0 x 10^9 per L)
b. Neutrophils (2.0 - 7.5 x 10^9 per L)
c. Monocytes (0.2 - 1.0 x 10^9 per L)
d. Eosinophils (0.04 - 0.4 x 10^9 per L)
e. Basophils (0 - 0.21 x 10^9 per L)
8. Participant has discontinued all disallowed concomitant medications for the required time prior to the first dose of study drug and is taking only those concomitant medications in doses and frequency allowed by the protocol;
9. Females of childbearing potential (FOCBP) must test negative for pregnancy prior to enrolment in the study;
10. Sexually active FOCBP and men, whose partners are FOCBP and who are not using adequate contraceptive methods, are required to use adequate contraceptive methods during participation in this trial.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants fulfilling any of the following criteria are not eligible for inclusion in this study.
1. History of any other rheumatic autoimmune disease, other than Sjogren’s syndrome;
2. Current or previous exposure to biological DMARDs within 3 months, or Infliximab within 6 months prior to the first dose of the study drug;
3. Use of high potency opioid analgesics (e.g., methadone, hydromorphone, morphine);
4. Use of oral antimicrobial drugs within 4 weeks prior to the first dose of the study drug;
5. Use of probiotic supplements within 2 weeks prior to the first dose of the study drug;
6. History of hypersensitivity to the study drug or its excipients or to drugs of similar classes, probiotics or any antibiotics commonly used to treat bacterial infections;
7. History of any infection requiring hospitalisation, parental antimicrobial therapy, or as otherwise judged clinically significant, within the 3 months prior to screening;
8. History of septicaemia or bacteraemia;
9. Use of any investigational drug and/or device within 4 weeks before randomisation or a period of 5 half-lives of the investigational drug, whichever is longer. Patients cannot participate in studies of other investigational compounds at any time during their participation in this study;
10. Current or recent history of uncontrolled clinically significant renal, hepatic, haematological, gastrointestinal, endocrine, metabolic (including uncontrolled clinically significant hypercholesterolemia), pulmonary, cardiac, or neurological disease;
11. History of, or signs and symptoms suggestive of any current, lymphoproliferative disease or lymphatic disorder, or history of malignancy of any known malignancy of any organ system with the past 5 years (except for basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed);
12. Those with known or suspected history of immunodeficiency;
13. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study;
14. Any planned surgical procedure during the treatment period, other than that deemed by the Study Coordinator to be minor and unlikely to impact on the study and will not require the use of antibiotics;
15. Females who are pregnant or breastfeeding or planning on becoming pregnant for the study period (treatment and follow-up periods);
16. History of alcohol or drug abuse with less than 6 months of abstinence prior to first dose of study drug;
17. Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect patient safety;
18. Inability or unwillingness to undergo repeated venepuncture (e.g., because of poor tolerability or lack of access to veins);
19. Inability or unwillingness to complete repeated stool collections.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/10/2022
Actual
21/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
64
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 309778 0
Commercial sector/Industry
Name [1] 309778 0
Servatus Ltd
Country [1] 309778 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Servatus Ltd
Address
12-14 Lomandra Place, Coolum Beach Qld, 4573
Country
Australia
Secondary sponsor category [1] 311154 0
None
Name [1] 311154 0
Address [1] 311154 0
Country [1] 311154 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309531 0
Metro North Health Human Research Ethics
Ethics committee address [1] 309531 0
Ethics committee country [1] 309531 0
Australia
Date submitted for ethics approval [1] 309531 0
04/11/2021
Approval date [1] 309531 0
09/12/2021
Ethics approval number [1] 309531 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114478 0
Prof Peter Nash
Address 114478 0
Rheumatology Research Unit at Coast Joint Care,
Maroochy Waters Shopping Centre
Denna St, Maroochydore QLD 4558
Country 114478 0
Australia
Phone 114478 0
+61 7 5443 1033
Fax 114478 0
Email 114478 0
drpnash@tpg.com.au
Contact person for public queries
Name 114479 0
Helen Brookes
Address 114479 0
Rheumatology Research Unit at Coast Joint Care,
Maroochy Waters Shopping Centre
Denna St, Maroochydore QLD 4558
Country 114479 0
Australia
Phone 114479 0
+61 7 5443 1033
Fax 114479 0
Email 114479 0
helen@coastjointcare.com
Contact person for scientific queries
Name 114480 0
Samantha Coulson
Address 114480 0
Servatus
12-14 Lomandra Place Coolum Beach Qld, 4573
Country 114480 0
Australia
Phone 114480 0
+61 7 5357 6830
Fax 114480 0
Email 114480 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 patient 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.