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

Tracking Information

• First Submitted Date: July 18, 2023
• First Posted Date: July 27, 2023
• Last Update Posted Date: January 19, 2024
• Actual Study Start Date: October 19, 2023
• Estimated Primary Completion Date: November 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 18, 2023)

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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 17, 2023)

• 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.
• 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).

Original Secondary Outcome Measures (submitted: July 18, 2023)

• Change in Disease Activity Score-28 joint C-Reactive Protein DAS28 (CRP) [ Time Frame: Baseline through week 4 ]
  Change from Baseline in DAS28 (CRP) Score at Week 6
• Change in Simplified Disease Activity Index (SDAI) Score over time [ Time Frame: Baseline through week 4 ]
  Baseline SDAI Score over time

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Arthritis, Rheumatoid

Intervention

Drug: R-2487

Probiotic

Other Name: Drug

Study Arms

Open Label

Probiotic

Intervention: Drug: R-2487

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 18, 2023): 36
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2026
• Estimated Primary Completion Date: November 2025 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05961592
• Other Study ID Numbers: RISE-2487-RA01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Rise Therapeutics LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Rise Therapeutics LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Rise Therapeutics LLC
• Verification Date: January 2024