Clinical trial NCT06005220: SBD121, a Synbiotic Medical Food for RA Management
Official title: A Randomised, Double Blind Placebo-controlled Trial Evaluating the Medical Food Synbiotic SBD121, Versus Placebo for the Clinical Dietary Management of Early Rheumatoid Arthritis.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rheumatoid Arthritis
Lead sponsor: Solarea Bio, Inc
Sponsor class: INDUSTRY
First posted: 2023-08-22
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The aim of this randomised, double-blind, placebo controlled clinical food trial is to determine if the medical food SBD121 Synbiotic (prebiotic and probiotic) will aid in the dietary management of symptoms of early rheumatoid arthritis (RA).


Eligibility criteria: Inclusion Criteria:

1. 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.
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 able to attend all scheduled visits and in the opinion of the Investigator be able to understand 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, diastolic blood pressure ≤ 90 mm Hg). One re-test is permitted.
9. 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.

Exclusion Criteria:

1. 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.
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 the study period.
4. Participant has undergone major surgery within last 3-months before screening or planned during the study period
5. 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.
6. 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).
7. Participant has a known history of any of the following (according to Investigator judgement and/or participant report):

   1. Gastric or intestinal dysmotility, slowed transit time, pancreatitis, or inflammatory bowel disease
   2. Known Hepatitis B or Hepatitis C infection, cirrhosis or chronic liver disease
   3. Underlying structural heart disease or previous history of endocarditis or valve replacement
   4. Rheumatic disease other than rheumatoid arthritis, including but not limited to psoriasis, spondyloarthritis, systemic lupus erythematosus, multiple sclerosis
   5. 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
   6. Any malignancy, with the exception of non-melanoma skin cancers, or other cancer more than 5-years ago
   7. Active tuberculosis (TB) within 3-months prior to Screening
   8. Any infection requiring hospitalisation, or as otherwise judged clinically significant, within 3-months prior to Screening
8. Presence of any of the following active conditions at Screening, or within 72 hours of the first administration of study test article:

   1. Clinically significant abnormal vital signs or physical examination abnormalities (other than those related to RA, such as joint swelling)
   2. 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
   3. Acute abdomen, colitis, or active GI disease
   4. Septicaemia or bacteraemia
   5. Uncontrolled diabetes mellitus, based on medical history and in response to query 'is your diabetes under control?'.
9. 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.
10. 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.
11. Corticosteroid use from 30 days prior to randomisation until final assessment visit will be exclusionary, with the following exceptions:

    1. 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.
    2. Topical, inhaled, or intranasal steroids are permitted
    3. Past use of oral or parenteral (\> 10 mg/d prednisone or equivalent) corticosteroids is allowed if not used within 1-month prior to randomisation.
12. 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.
13. Any of the following abnormal findings on Screening or Baseline laboratory tests (one re-test per timepoint permitted):

    1. 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.
    2. Neutrophils \< 1500/µl (1.5 x109/L)
    3. Platelets \< 100 x 10³/µl (100 x 109/L)
    4. Haemoglobin \< 9.0 g/dl (90 g/L)
    5. Serum Creatinine \> 1.5 x ULN
    6. Glomerular filtration rate (GFR) of \< or = 40 mL/minute
    7. Aspartate aminotransferase (AST) \> 3 x ULN
    8. Alanine aminotransferase (ALT) \> 3 x ULN
    9. Total Bilirubin \> 1.5 x ULN
14. 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
15. If the participant has been in a recent experimental trial, these must have been completed not less than 60 days prior to this study.

Primary outcomes:
measure: American College of Rheumatology 20 (ACR-20)
timeFrame: 16 Weeks
Secondary outcomes:
measure: Safety by Adverse Events
timeFrame: 16-weeks
measure: Tolerability by GITQ
timeFrame: 16-weeks
measure: American College of Rheumatology 20 (ACR-20)
timeFrame: 8 weeks
measure: American College of Rheumatology 50 (ACR-50)
timeFrame: 8-weeks, 16-weeks
measure: American College of Rheumatology 70 (ACR-70)
timeFrame: 8-weeks, 16-weeks
measure: Disease Activity Score 28 - Eosinophil Sedimentation Rate (DAS28 - ESR)
timeFrame: 8-weeks, 16-weeks
measure: Disease Activity Score 28 - C-Reactive Protein (DAS28 - CRP)
timeFrame: 8-weeks, 16-weeks
measure: Disease Activity Score 28 - Eosinophil Sedimentation Rate - Low Disease Activity (DAS28 - ESR - LDA)
timeFrame: 8-weeks, 16-weeks
measure: Disease Activity Score 28 - C-Reactive Protein - Low Disease Activity (DAS28 - CRP LDA)
timeFrame: 8-weeks, 16-weeks
measure: Disease Activity Score 28 - Eosinophil Sedimentation Rate - Remission (DAS28 - ESR Remission)
timeFrame: 8-weeks, 16-weeks
measure: Disease Activity Score 28 - C-Reactive Protein - Remission (DAS28 - CRP Remission)
timeFrame: 8-weeks, 16-weeks
measure: C-Reactive Protein (CRP)
timeFrame: 8-weeks, 16-weeks
measure: Eosinophil Sedimentation Rate (ESR)
timeFrame: 8-weeks, 16-weeks
measure: Zonulin
timeFrame: 8-weeks, 16-weeks
measure: Reduce or discontinue use of oral corticosteroids
timeFrame: 8-weeks, 16-weeks
measure: Reduce or discontinue use of oral NSAIDs
timeFrame: 8-weeks, 16-weeks
Other outcomes:
measure: Microbiome functional composition by shotgun metagenomics
timeFrame: 16-weeks
measure: Microbiome taxonomic composition by shotgun metagenomics
timeFrame: 16-weeks
Locations:
city: Canberra
country: Australia
facility: Paratus Clinical Canberra
state: Australian Capital Territory
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Genesis Research Services
state: New South Wales
city: Parramatta
country: Australia
facility: BJC Health
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Melbourne
country: Australia
facility: St. Vincents Hospital Melbourne
state: Victoria
city: St. Albans
country: Australia
facility: Western Health
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Trials
state: Western Australia
city: Perth
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Lom
country: Bulgaria
facility: Diagnostic Consultative Center 1 - Lom EOOD
city: Ruse
country: Bulgaria
facility: Medical Center - Teodora EOOD
city: Sofia
country: Bulgaria
facility: MHAT Lyulin EAD, Department of Rheumatology
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center XIV - Sofia EOOD
city: Vrasta
country: Bulgaria
facility: Medical Center Tera Medico EOOD
city: Chisinau
country: Moldova, Republic of
facility: RTL SM SRL/ IMSP Institutul de Cardiologie
city: Chisinau
country: Moldova, Republic of
facility: Spitalul Clinic Republican Timofei Mosneaga
city: Auckland
country: New Zealand
facility: Aotearoa Clinical Trials
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials
city: Nelson
country: New Zealand
facility: Southern Clinical Trials
Study officials:
affiliation: Southern Star Research
name: Maureen Stanley
role: STUDY_DIRECTOR
References: