R-2487 in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The goal of this study is to determine the safety and tolerability of orally taken probiotic (R-2487) in patients with Rheumatoid Arthritis. Patients will take an oral dosage of probiotic (R-2487) and physicians will assess and measure their Rheumatoid Arthritis. Blood and fecal evaluations of inflammation and assessment of probiotic (R-2487) on fecal level will also be measured.

Official Title
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A Single and Repeat Dosing Study of the Safety, Drug Exposure and Clinical Activity of R-2487 in Patients With Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: R-2487


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-75 years (Inclusive). Able to provide written informed consent. Men or women (not nursing or pregnant) who have active RA, defined as symptoms of RA prior to screening and have satisfied the ACR/EULAR 2010 criteria for the classification of RA prior to signing the informed consent. Subjects must have a CDAI > 10.0 at screening and have at least 3 tender and at least 3 swollen joints (excluding distal interphalangeal) at screening and at Day 1, based on the DAS28 joint count. Subjects may be able to be on hydroxychloroquine, methotrexate, and leflunomide. Sulfasalazine use is not permitted. Subjects may have received targeted synthetic DMARDs such as tofacitinib, baricitinib, and investigational therapies for RA if they have been washed out for 1 month prior to screening. Subjects receiving oral corticosteroids must be on a stable dose and at the equivalent of ≤10 mg prednisone daily for at least 4 weeks. Subjects may not receive an IM, IV or IA administration of a corticosteroid within 4 weeks prior to screening visit or initiation of therapy. All male and female subjects who are biologically capable of having children must agree to use a medically acceptable method of birth control for the duration of the study. All female subjects who are biologically capable of having children must have a negative pregnancy test result before administration of study drug. Any pregnancy that occurs in the female partner of a male subject in the trial must be reported if it occurs at any time during the study. Refrain from receiving any type of vaccinations during the study period (to include but not limited to influenza, COVID, shingles, tetanus, hepatitis, pneumonia, HPV, DPT, MMR, and polio). Exclusion Criteria: Pregnancy (females, unless surgically sterile or at least two years post- menopausal must have a negative serum pregnancy test within 14 days prior to receiving the study drug and a negative urine pregnancy test on Study Day 0 before receiving the study drug). Nursing mothers. Subjects with autoimmune disease other than RA [e.g., psoriasis, systemic lupus erythematosus (SLE), vasculitis, seronegative spondylarthritis, Inflammatory Bowel Disease, Sjogren's syndrome] or currently active fibromyalgia. Subjects should not receive any of the following medications: Rituximab within 12 months prior to Day 1, Abatacept within 3 months prior to Day 1, Infliximab, Adalimumab, Certolizumab, Tocilizumab, Cyclosporine, or Mycophenolate mofetil within 2 months prior to Day 1, or Etanercept, Anakinra, Immunoglobulin, or blood products within 28 days prior to Day 1 Prior immunotherapy, including systemic corticosteroids, such prednisone, biologics, Janus kinase (JAK) inhibitors (such as tofacitinib, baricitinib or upadacitinib), ozanimod, or investigational therapy must have completed at least 5 half-lives or 30 days, whichever is longer, prior to Day 0, unless otherwise specified. In the case of cell-depleting therapies, such as B or T cell depletion, cell counts must have recovered to acceptable or baseline levels (use of licensed agents for indications not listed in the package insert is permitted). Prior history of or current inflammatory joint disease other than RA (such as psoriatic arthritis, gout, reactive arthritis, Lyme disease). Subjects at risk for tuberculosis (TB) defined as follows: Current clinical, radiographic or laboratory evidence of active TB. Chest x-rays (posterior, anterior and lateral) obtained within the 3 months prior to obtaining written informed consent will be permitted but the images must be available and reviewed by the investigator. TB testing (IFN-gamma release assay or PPD) performed in the past month prior to Screening will be accepted; however, a copy of the report must be placed in the subject binder. A history of active TB. Subjects with a positive TB screening test indicative of latent TB including subjects currently being treated for latent tuberculosis infection (LTBI) will not be eligible for the study. Subjects with recent acute infection defined as: Any acute infection within 60 days prior to randomization that required hospitalization or treatment with parenteral antibiotics, Any acute infection within 30 days prior to randomization that required oral antimicrobial or antiviral therapy, Subjects with history of chronic or recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis etc.), Subjects with any history of infection of a joint prosthesis or artificial joint, Subjects who have a history of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis), Subjects with history of recurrent herpes zoster (more than 1 episode) or disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic zoster will be excluded, Symptoms of herpes zoster or herpes simplex must have resolved more than 60 days prior to screening, Subjects with history of primary immunodeficiency. Subjects with history of Human Immunodeficiency Virus (HIV) infection or who tested positive for HIV. Evidence of infection with hepatitis B virus (HBV), hepatitis C virus (C), human immunodeficiency virus (HIV)-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at screening. Subjects who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non- metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Subjects who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations. Current clinical findings of a history of a demyelinating disorder. New York Heart Association (NYHA) Class III or IV heart failure. Subjects who have undergone a major surgical procedure within the 60 days prior to enrollment. Subjects for whom 5 or more joints cannot be assessed for tenderness or swelling (i.e. due to surgery, fusion, amputation, etc.). Current clinical findings of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, endocrine, neurological, or cerebral disease with laboratory values as following: Hemoglobin level < 9.0 g/dL, Absolute white blood cell (WBC) count of <3.0×109/L (<3000/mm3), or absolute neutrophil count of <1.2×109/L (<1200/mm3), or absolute lymphocyte count of <0.8×109/L (<800/mm3), Thrombocytopenia, defined by platelet count <100×109/L (<100,000/mm3), Chronic kidney disease defined as Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2, based on the age-appropriate calculation, Proteinuria ≥3+, Total bilirubin (T-bili), aspartate aminotransferase (AST), alanine aminotransferase (ALT) more than 1.5 times upper limit of normal (ULN) Previously diagnosed hepatic cirrhosis (Child Pugh A or higher) or previously diagnosed significant liver fibrosis (> F3). Any form of vaccination in the last 30 days, to include but not limited to influenza, COVID, shingles, tetanus, hepatitis, pneumonia, HPV, DPT, MMR, and polio.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open Label<br>Probiotic | Drug: R-2487<br>* Probiotic<br>* Other names: Drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events and their relationship to R-2487 (probiotic) administration | To assess the number of participants with treatment-related adverse events after taking R-2487 (probiotic) | Baseline through week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP) | Change from Baseline in Disease Activity Score-28 joint C- Reactive Protein (DAS28-CRP) Score at Week 6 Describes severity of rheumatoid arthritis using clinical and laboratory data in swollen and tender joints. A score between 0 to 10 with the higher number indicating more active disease. | Baseline through week 4 | 
| Change in Simplified Disease Activity Index (SDAI) Score over time | Baseline Simplified Disease Activity Index (SDAI) Score over time. The Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity [visual analogue scale (VAS) 0-10 cm] and level of C-reactive protein (mg/dl, normal <1 mg/dl). | Baseline through week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis, Rheumatoid