SBD121, a Synbiotic Medical Food for RA Management

Inclusion Criteria:

1. Willing and able to provide written informed consent prior to the performance of anystudy-specific procedure and willing to comply with the protocol and report oncompliance and side effects during study period.

2. Male or female aged 18 - 75 years inclusive at the time of consent.

3. The participant must have newly diagnosed RA, not exceeding 1-year from diagnosis

4. The participant must have been taking methotrexate (MTX) for treatment of RA for ≤ 75 days before baseline, or will be commencing MTX at the same time as baseline (within range 15 to 25 mg inclusive, recommended target dose of 20mg).

5. The participant must have active RA meeting classification criteria according to the 2010 ACR/EULAR guidelines with a score equal to or greater than 6/10 at screening (11). (Seropositivity is not required).

6. The participant must be available throughout entire study period, willing and ableto attend all scheduled visits and in the opinion of the Investigator be able tounderstand and comply with planned study procedures.

7. Body Mass Index (BMI) between 18.5 and 40 kg/m2

8. Normal cardiovascular parameters (systolic blood pressure ≤ 150 mm Hg, diastolicblood pressure ≤ 90 mm Hg). One re-test is permitted.

9. Women of childbearing potential must have a negative serum pregnancy test atscreening and negative urine pregnancy test pre-first administration, on Day 1, andmust agree to remain sexually abstinent, or use medically effective contraception (refer to Appendix 11.1), or have a partner who is sterile or same-sex, fromScreening until end of study. Males must not be planning to father children ordonate sperm for the duration of the study.

Exclusion Criteria:

1. Participant is currently taking any probiotic or prebiotic supplements, or has takenthem in the past 7 days, or is unwilling to avoid taking probiotic/prebioticsupplements for the duration of the study.

2. Participant has any known or suspected allergies to probiotics or prebiotics.

3. Participant has taken oral or parenteral antibiotics within 21 days of screening,requires antibiotics pre-first dose, or is likely to require antibiotics during thestudy period.

4. Participant has undergone major surgery within last 3-months before screening orplanned during the study period

5. Participant is a current or past smoker and/or user of nicotine replacementtherapies (including vaping), that in the documented opinion of the Investigator,may adversely affect participation in the study, safety, and/or study outcomes.

6. Participant has a past or current history of drug and/or alcohol abuse at the timeof enrolment (the use of illegal drugs or the use of prescription orover-the-counter drugs or alcohol for purposes other than those for which they aremeant to be used, or in excessive amounts).

7. Participant has a known history of any of the following (according to Investigatorjudgement and/or participant report):

8. Gastric or intestinal dysmotility, slowed transit time, pancreatitis, orinflammatory bowel disease

9. Known Hepatitis B or Hepatitis C infection, cirrhosis or chronic liver disease

10. Underlying structural heart disease or previous history of endocarditis orvalve replacement

11. Rheumatic disease other than rheumatoid arthritis, including but not limited topsoriasis, spondyloarthritis, systemic lupus erythematosus, multiple sclerosis

12. Immunosuppressed, including: known HIV positive; solid organ or stem celltransplant recipient; taking any oral or parenteral immunosuppressive therapy;neutrophil count <500/mm3; or anticipated drop in the neutrophil count to <500/mm3

13. Any malignancy, with the exception of non-melanoma skin cancers, or othercancer more than 5-years ago

14. Active tuberculosis (TB) within 3-months prior to Screening

15. Any infection requiring hospitalisation, or as otherwise judged clinicallysignificant, within 3-months prior to Screening

16. Presence of any of the following active conditions at Screening, or within 72 hoursof the first administration of study test article:

17. Clinically significant abnormal vital signs or physical examinationabnormalities (other than those related to RA, such as joint swelling)

18. Febrile illness (temp. > 37.5 degrees Celsius), or one or more episodes ofdiarrhoea within 72 hours of the first dose of study test article

19. Acute abdomen, colitis, or active GI disease

20. Septicaemia or bacteraemia

21. Uncontrolled diabetes mellitus, based on medical history and in response toquery 'is your diabetes under control?'.

22. Current treatment with any Disease Modifying Arthritis Drug (DMARD) other thanmethotrexate including but not limited to, hydroxychloroquine, sulfasalazine, andminocycline leflunomide, gold compounds, azathioprine, or cyclosporine will beexclusionary if used within 30 days prior to randomisation.

23. Current or past treatment with any biologic agent including but not limited to tumornecrosis factor (TNF) inhibitors: etanercept, infliximab, adalimumab; interleukin 1 (IL-1) inhibitors: anakinra; lymphocyte directed: abatacept, rituximab; Janus kinase (JAK) inhibitors: tofacitinib; interleukin 17 (IL-17) inhibitors; Interleukin 23 (IL-23) inhibitors.

24. Corticosteroid use from 30 days prior to randomisation until final assessment visitwill be exclusionary, with the following exceptions:

25. Oral corticosteroids in low doses (≤ 10 mg/d prednisone or equivalent) will beallowed if stable for 1-month prior to randomisation. Reduction of dose or useof oral corticosteroids is permissible throughout the study.

26. Topical, inhaled, or intranasal steroids are permitted

27. Past use of oral or parenteral (> 10 mg/d prednisone or equivalent)corticosteroids is allowed if not used within 1-month prior to randomisation.

28. Women only - pregnant, planning on becoming pregnant during the trial,breastfeeding, positive urine pregnancy test during Screening or within 24 hours offirst administration of study test article.

29. Any of the following abnormal findings on Screening or Baseline laboratory tests (one re-test per timepoint permitted):

30. White blood cells (WBCs) < lower limit of normal (LLN) or > upper limit ofnormal (ULN). If WBC is documented within normal range prior to commencingsteroids and is deemed by the Investigator as elevated at screening due torecent addition of these drugs and not related to any other comorbidities, thenmay be suitable to proceed.

31. Neutrophils < 1500/µl (1.5 x109/L)

32. Platelets < 100 x 10³/µl (100 x 109/L)

33. Haemoglobin < 9.0 g/dl (90 g/L)

34. Serum Creatinine > 1.5 x ULN

35. Glomerular filtration rate (GFR) of < or = 40 mL/minute

36. Aspartate aminotransferase (AST) > 3 x ULN

37. Alanine aminotransferase (ALT) > 3 x ULN

38. Total Bilirubin > 1.5 x ULN

39. Any other condition that in the opinion of the investigator would jeopardize thesafety or rights of the volunteer participating in the study or would make itunlikely the volunteer could complete the study

40. If the participant has been in a recent experimental trial, these must have beencompleted not less than 60 days prior to this study.