SBD121, a Synbiotic Medical Food for RA Management

Prior treatment

• Participant is currently taking any probiotic or prebiotic supplements, or has taken them in the past 7 days, or is unwilling to avoid taking probiotic/prebiotic supplements for the duration of the study.
• Participant has undergone major surgery within last 3-months before screening or planned during the study period
• Participant is a current or past smoker and/or user of nicotine replacement therapies (including vaping), that in the documented opinion of the Investigator, may adversely affect participation in the study, safety, and/or study outcomes.
• Current treatment with any Disease Modifying Arthritis Drug (DMARD) other than methotrexate including but not limited to, hydroxychloroquine, sulfasalazine, and minocycline leflunomide, gold compounds, azathioprine, or cyclosporine will be exclusionary if used within 30 days prior to randomisation.
• Corticosteroid use from 30 days prior to randomisation until final assessment visit will be exclusionary, with the following exceptions:
  • Oral corticosteroids in low doses (≤ 10 mg/d prednisone or equivalent) will be allowed if stable for 1-month prior to randomisation. Reduction of dose or use of oral corticosteroids is permissible throughout the study.
  • Topical, inhaled, or intranasal steroids are permitted
  • Past use of oral or parenteral (\> 10 mg/d prednisone or equivalent) corticosteroids is allowed if not used within 1-month prior to randomisation.
• If the participant has been in a recent experimental trial, these must have been completed not less than 60 days prior to this study.

Other illness

• Participant has any known or suspected allergies to probiotics or prebiotics.
• Participant has a past or current history of drug and/or alcohol abuse at the time of enrolment (the use of illegal drugs or the use of prescription or over-the-counter drugs or alcohol for purposes other than those for which they are meant to be used, or in excessive amounts).
• Presence of any of the following active conditions at Screening, or within 72 hours of the first administration of study test article:
  • Clinically significant abnormal vital signs or physical examination abnormalities (other than those related to RA, such as joint swelling)
  • Febrile illness (temp. \> 37.5 degrees Celsius), or one or more episodes of diarrhoea within 72 hours of the first dose of study test article
  • Acute abdomen, colitis, or active GI disease
  • Septicaemia or bacteraemia
  • Uncontrolled diabetes mellitus, based on medical history and in response to query 'is your diabetes under control?'.
• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer participating in the study or would make it unlikely the volunteer could complete the study

Lab values

• Participant has a known history of any of the following (according to Investigator judgement and/or participant report):
  • Gastric or intestinal dysmotility, slowed transit time, pancreatitis, or inflammatory bowel disease
  • Known Hepatitis B or Hepatitis C infection, cirrhosis or chronic liver disease
  • Underlying structural heart disease or previous history of endocarditis or valve replacement
  • Rheumatic disease other than rheumatoid arthritis, including but not limited to psoriasis, spondyloarthritis, systemic lupus erythematosus, multiple sclerosis
  • Immunosuppressed, including: known HIV positive; solid organ or stem cell transplant recipient; taking any oral or parenteral immunosuppressive therapy; neutrophil count \<500/mm3; or anticipated drop in the neutrophil count to \<500/mm3
  • Any malignancy, with the exception of non-melanoma skin cancers, or other cancer more than 5-years ago
  • Active tuberculosis (TB) within 3-months prior to Screening
  • Any infection requiring hospitalisation, or as otherwise judged clinically significant, within 3-months prior to Screening
• Current or past treatment with any biologic agent including but not limited to tumor necrosis 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.
• Any of the following abnormal findings on Screening or Baseline laboratory tests (one re-test per timepoint permitted):
  • White blood cells (WBCs) \< lower limit of normal (LLN) or \> upper limit of normal (ULN). If WBC is documented within normal range prior to commencing steroids and is deemed by the Investigator as elevated at screening due to recent addition of these drugs and not related to any other comorbidities, then may be suitable to proceed.
  • Neutrophils \< 1500/µl (1.5 x109/L)
  • Platelets \< 100 x 10³/µl (100 x 109/L)
  • Haemoglobin \< 9.0 g/dl (90 g/L)
  • Serum Creatinine \> 1.5 x ULN
  • Glomerular filtration rate (GFR) of \< or = 40 mL/minute
  • Aspartate aminotransferase (AST) \> 3 x ULN
  • Alanine aminotransferase (ALT) \> 3 x ULN
  • Total Bilirubin \> 1.5 x ULN

Other

• Participant has taken oral or parenteral antibiotics within 21 days of screening, requires antibiotics pre-first dose, or is likely to require antibiotics during the study period.
• Women only - pregnant, planning on becoming pregnant during the trial, breastfeeding, positive urine pregnancy test during Screening or within 24 hours of first administration of study test article.

• Willing and able to provide written informed consent prior to the performance of any study-specific procedure and willing to comply with the protocol and report on compliance and side effects during study period.
• Male or female aged 18 - 75 years inclusive at the time of consent.
• The participant must have newly diagnosed RA, not exceeding 1-year from diagnosis
• 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).
• 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).
• The participant must be available throughout entire study period, willing and able to attend all scheduled visits and in the opinion of the Investigator be able to understand and comply with planned study procedures.
• Body Mass Index (BMI) between 18.5 and 40 kg/m2
• Normal cardiovascular parameters (systolic blood pressure ≤ 150 mm Hg, diastolic blood pressure ≤ 90 mm Hg). One re-test is permitted.
• Women of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test pre-first administration, on Day 1, and must 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, from Screening until end of study. Males must not be planning to father children or donate sperm for the duration of the study.