Probiotic R-2487 for Rheumatoid Arthritis

(R-2487-RA01 Trial)

Recruiting at 5 trial locations

Overseen By Christian Freguia, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Rise Therapeutics LLC

Must be taking: Hydroxychloroquine, Methotrexate, Leflunomide

Must not be taking: Rituximab, Abatacept, Infliximab, others

Disqualifiers: Autoimmune diseases, Active infections, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

73 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of a new probiotic treatment, R-2487, for individuals with Rheumatoid Arthritis (RA). Participants will take the probiotic orally, and researchers will assess its effects on RA symptoms and overall inflammation. The study includes different groups, with participants taking the treatment for either four or six weeks. Individuals with active RA, experiencing at least three tender and swollen joints, may be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial allows participants to continue taking certain medications like hydroxychloroquine, methotrexate, and leflunomide, but not sulfasalazine. If you have been on targeted synthetic DMARDs or certain other medications, you may need to stop them for a specific period before joining the trial. It's best to discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that R-2487, an oral probiotic, is safe and well-tolerated by people with rheumatoid arthritis. In earlier studies, this treatment not only proved safe but also helped reduce disease symptoms. Participants experienced improvements without major side effects.

For those with secondary Sjogren's Syndrome, similar safety results emerged. The treatment maintained a good safety record, consistent with previous research findings.

As this trial is in its early stage, it primarily focuses on assessing safety and tolerability. This phase involves close monitoring to ensure participant safety and to identify any negative reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Rheumatoid Arthritis?

Unlike the standard treatments for rheumatoid arthritis, which often include medications like methotrexate and biologics targeting immune pathways, Probiotic R-2487 introduces a novel approach by utilizing beneficial bacteria. Researchers are excited about this treatment because it potentially offers a natural way to modulate the immune system without the side effects associated with traditional drugs. Additionally, R-2487 could improve gut health, which has been increasingly linked to autoimmune conditions like rheumatoid arthritis. This innovative mechanism provides hope for a more holistic and less invasive treatment option.

What evidence suggests that this treatment might be an effective treatment for Rheumatoid Arthritis?

Research has shown that R-2487 holds promise for treating rheumatoid arthritis. In animal studies, R-2487 reduced arthritis symptoms by lowering inflammation. It achieves this by increasing Tregs, a type of cell that helps maintain immune system balance. This can decrease inflammatory cytokines, substances in the body that often cause inflammation. R-2487 is designed for oral administration to help balance the immune system and improve disease outcomes. In this trial, participants will receive R-2487 for either four or six weeks. Early findings suggest it may also benefit patients with secondary Sjogren's Syndrome, a condition often linked to rheumatoid arthritis. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-75 with active Rheumatoid Arthritis, not pregnant or nursing, who agree to use birth control and avoid vaccinations during the study. Participants must have a certain level of disease activity and can be on some RA medications but must have stopped others for specified times before joining.

Inclusion Criteria

I stopped taking certain RA medications like tofacitinib a month ago.

I will not get any vaccines during the study, including flu or COVID shots.

I have more than 3 tender and swollen joints and a CDAI score over 10.

Exclusion Criteria

I have had active tuberculosis in the past.

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

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)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an oral dosage of probiotic (R-2487) and are assessed for safety and tolerability

4 weeks

Weekly visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• R-2487

Trial Overview The trial is testing R-2487, an oral probiotic, for safety and effectiveness in treating Rheumatoid Arthritis. Patients' symptoms will be monitored through blood tests and assessments of inflammation in the body.

How Is the Trial Designed?

Group I: Six (6) week open label dose for Rheumatoid Arthritis patients Experimental Treatment 1 Intervention

R-2487 DP administered daily for 42 days

Group II: Four (4) week open label dose for Rheumatoid Arthritis with Secondary Sjorgrens Syndrome patients Experimental Treatment 1 Intervention

R-2487 DP administered daily for 28 days

Group III: Four (4) week open label dose for Rheumatoid Arthritis patients Experimental Treatment 1 Intervention

R-2487 DP administered daily for 28 days

Who Is Running the Clinical Trial?

Rise Therapeutics LLC

Lead Sponsor

Trials

5

Recruited

180+

Published Research Related to This Trial

Patients with rheumatoid arthritis (RA) showed significant dysbiosis in their colon microbiota, characterized by reduced levels of beneficial bacteria like Bacteroides, Bifidobacterium, and Lactobacillus, and an overgrowth of harmful bacteria such as Klebsiella and Staphylococcus.

The use of a eubiotic treatment (bifiform) effectively corrected the dysbiosis, increasing the populations of beneficial bacteria and selectively reducing harmful bacteria, suggesting a potential therapeutic approach for managing microbiota imbalances in RA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[THE USE OF PROBIOTICS IN PATIENTS WITH RHEUMATOID ARTHRITIS]. Kuchmak, OB., Klymnyuk, SI., Romanyuk, LB., et al.[2020]

Probiotics may be an effective therapeutic intervention for individuals with inflammatory arthritis, although the specific effectiveness was not detailed in the abstract.

The review also aims to assess the safety of probiotics by examining reported adverse effects, indicating a focus on both efficacy and safety in their use for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of probiotics in the management of inflammatory arthritis: a systematic review protocol. Lowe, J., Briggs, A., Whittle, S., et al.[2023]

A study involving 93 rheumatoid arthritis (RA) patients and 16 healthy subjects found that the gut microbiome composition differs significantly based on rheumatoid factor (RF) levels, with lower levels of beneficial Bifidobacterium in RF-high patients.

The specific strain Bifidobacterium longum RAPO showed promise in reducing RA symptoms in mouse models by inhibiting IL-17 production and other inflammatory markers, suggesting it could be a potential therapeutic option for RA that warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels. Jeong, Y., Jhun, J., Lee, SY., et al.[2021]

Current research suggests a potential link between the human microbiota and the development of rheumatoid arthritis (RA), particularly through mechanisms like citrullination and immune system changes.

Clinical trials on probiotics for RA have been small and short-term, showing some statistically significant changes, but no consistent or meaningful improvements in patient outcomes have been established, indicating a need for better trial designs to assess their true efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Probiotic Supplements Improve Outcomes in Rheumatoid Arthritis? Schorpion, A., Kolasinski, SL.[2022]

In a pilot study involving 45 patients with rheumatoid arthritis, the probiotic Bacillus coagulans GBI-30, 6086 showed a statistically significant improvement in pain and functional capacity compared to placebo, indicating its potential as an effective adjunct treatment.

The study reported no adverse events related to the probiotic, suggesting it is a safe option for patients with rheumatoid arthritis when used alongside standard medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial. Mandel, DR., Eichas, K., Holmes, J.[2022]

In a meta-analysis of 4 randomized controlled trials involving 153 participants with rheumatoid arthritis, probiotics did not significantly alter inflammatory markers or oxidative stress indices compared to placebo.

However, there was a significant improvement in disease activity scores (DAS) with probiotics, suggesting a potential benefit in managing symptoms of rheumatoid arthritis, though more research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of probiotic supplementation in rheumatoid arthritis: a meta-analysis of randomized, controlled trials. Aqaeinezhad Rudbane, SM., Rahmdel, S., Abdollahzadeh, SM., et al.[2021]

In a study involving 46 rheumatoid arthritis patients, supplementation with the probiotic Lactobacillus casei 01 for 8 weeks did not significantly improve oxidative stress markers compared to a placebo.

Despite the probiotic's known health benefits, including antioxidant properties, there were no notable differences in oxidative stress indices such as malondialdehyde (MDA) or total antioxidant capacity (TAC) between the probiotic and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Probiotic Supplementation on Oxidative Stress Indices in Women with Rheumatoid Arthritis: A Randomized Double-Blind Clinical Trial. Vaghef-Mehrabany, E., Homayouni-Rad, A., Alipour, B., et al.[2022]

In a study involving 60 women with rheumatoid arthritis, taking Lactobacillus casei for 8 weeks did not lead to significant changes in serum lipid levels, including total cholesterol and triglycerides.

The results suggest that Lactobacillus casei 01 is not effective in improving lipid profiles in RA patients, indicating a need for further research with different probiotic strains or formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of probiotic supplementation on lipid profile of women with rheumatoid arthritis: A randomized placebo-controlled clinical trial. Vaghef-Mehrabany, E., Vaghef-Mehrabany, L., Asghari-Jafarabadi, M., et al.[2022]

In a three-month study involving 29 patients with rheumatoid arthritis, probiotics did not show a statistically significant improvement in the ACR20 response compared to placebo, indicating limited efficacy as an adjunctive therapy.

However, the probiotic group did experience a significant improvement in their Health Assessment Questionnaire (HAQ) scores, suggesting some functional benefits despite the lack of overall clinical improvement in RA symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheumatoid arthritis. Pineda, Mde L., Thompson, SF., Summers, K., et al.[2022]

In a clinical trial involving 46 patients with rheumatoid arthritis, supplementation with Lactobacillus casei 01 for 8 weeks significantly reduced disease activity and inflammatory cytokines compared to a placebo group.

The probiotic treatment led to a decrease in proinflammatory cytokines like tumor necrosis factor-α and interleukin-6, while increasing the regulatory cytokine interleukin-10, suggesting a beneficial effect on inflammation in RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Vaghef-Mehrabany, E., Alipour, B., Homayouni-Rad, A., et al.[2022]

Citations

1. acrabstracts.org acrabstracts.org/abstract/r-2487-a-synthetic-biology-based-oral-immunotherapy-promotes-treg-mediated-immune-rebalancing-and-reduces-disease-activity-in-rheumatoid-arthritis-patients/

R-2487, a Synthetic Biology-Based Oral Immunotherapy ... These studies showed that oral administration of R-2487 expanded Tregs, reduced inflammatory cytokines, and improved disease outcomes via bystander tolerance in ...

2. withpower.com withpower.com/trial/phase-1-arthritis-rheumatoid-10-2023-b7313

Probiotic R-2487 for Rheumatoid Arthritis Research shows that probiotics, like R-2487, can help improve symptoms of rheumatoid arthritis by reducing inflammation and disease activity. Some studies found ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/rise-rheumatoid-arthritis-trial/

Rise Therapeutics begins rheumatoid arthritis therapy trial The first-in-human study will evaluate R-2487's pharmacodynamics, safety and clinical activity in rheumatoid arthritis patients across various ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05961592

NCT05961592 | R-2487 in Patients With Rheumatoid Arthritis The goal of this study is to determine the safety and tolerability of orally taken probiotic (R-2487) in patients with Rheumatoid Arthritis.

5. reporter.nih.gov reporter.nih.gov/project-details/11109650

RePORT RePORTER - National Institutes of Health (NIH) | ... R-2487) and validated its efficacy in multiple autoimmune models. R-2487 was effective at reducing arthritis symptoms in animal model studies, along with ...

6. reporter.nih.gov reporter.nih.gov/search/ByzpZZrVd0iUH_2DyhLbvw/project-details/11109650

RePORT RePORTER - National Institutes of Health (NIH) | This Fast Track application is focused on obtaining human validation for R-2487 by completing a first-in-human Phase 1 RA proof-of-concept clinical trial.

7. app.trialscreen.org app.trialscreen.org/trials/phase-1-r-2487-patients-rheumatoid-arthritis-trial-nct05961592

R-2487 in Patients With Rheumatoid Arthritis Benefits: Participants will receive close monitoring of their rheumatoid arthritis condition by medical professionals. The study may provide valuable ...