R-2487 in Patients With Rheumatoid Arthritis (R-2487-RA01)

• ClinicalTrials.gov Identifier: NCT05961592
• Recruitment Status: Recruiting
• First Posted: July 27, 2023
• Last Update Posted: January 19, 2024
• Sponsor: Rise Therapeutics LLC
• Information provided by (Responsible Party): Rise Therapeutics LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Arthritis, Rheumatoid	Drug: R-2487	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single and Repeat Dosing Study of the Safety, Drug Exposure and Clinical Activity of R-2487 in Patients With Rheumatoid Arthritis
• Actual Study Start Date: October 19, 2023
• Estimated Primary Completion Date: November 2025
• Estimated Study Completion Date: January 2026

Arms and Interventions

Arm	Intervention/treatment
Open Label; Probiotic	Drug: R-2487; Probiotic; Other Name: Drug

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of adverse events and their relationship to R-2487 (probiotic) administration [ Time Frame: Baseline through week 4 ]
   To assess the number of participants with treatment-related adverse events after taking R-2487 (probiotic)

Secondary Outcome Measures :

1. Change in Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP) [ Time Frame: Baseline through week 4 ]
   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.
2. Change in Simplified Disease Activity Index (SDAI) Score over time [ Time Frame: Baseline through week 4 ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Janet Stephens, PhD; 6504178556; jstephens@risetherapeutics.com

Contact: Christian Freguia, PhD; 2159231818; cfreguia@risetherapeutics.com

Locations

United States, Florida

St.Jude Clinical Research; Recruiting

Doral, Florida, United States, 33172

Contact: Shelia Linares, BSN 305-507-2273 slinares@stjudeclinicalresearch.com

Principal Investigator: Gustavo Torres, MD

AP Medical Research; Recruiting

Miami, Florida, United States, 33165

Contact: Simon Gomez 305-400-8899 simon@apmedresearch.com

Principal Investigator: Ramon Sastre, MD

United States, New Hampshire

Dartmouth Hitchcock Medical Center (DHMC); Not yet recruiting

Lebanon, New Hampshire, United States, 03766

Contact: Jill Brooker, RN 603-650-4717 jill.b.brooker@hitchcock.org

Principal Investigator: William Rigby, MD

United States, Pennsylvania

Altoona Center for Research; Recruiting

Duncansville, Pennsylvania, United States, 16635

Contact: Tracey Madonna, MA 814-693-0300 ext 147 traceymadonna@altoonaresearch.com

Contact: Brenda Endress 8146930300 ext 202 brendaearnest@altoonaresearch.com

Principal Investigator: Alan Kivitz, MD

Sponsors and Collaborators

Rise Therapeutics LLC

More Information

• Responsible Party: Rise Therapeutics LLC
• ClinicalTrials.gov Identifier: NCT05961592
• Other Study ID Numbers: RISE-2487-RA01
• First Posted: July 27, 2023
• Last Update Posted: January 19, 2024
• Last Verified: January 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rise Therapeutics LLC:

Arthritis, Rheumatoid

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases