Clinical trial NCT05961592: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid
Lead sponsor: Rise Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2023-07-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence and severity of adverse events and their relationship to R-2487 (probiotic) administration
timeFrame: Baseline through week 4
Secondary outcomes:
measure: Change in Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP)
timeFrame: Baseline through week 4
measure: Change in Simplified Disease Activity Index (SDAI) Score over time
timeFrame: Baseline through week 4
Other outcomes:
Locations:
city: Doral
country: United States
facility: St.Jude Clinical Research
state: Florida
city: Miami
country: United States
facility: AP Medical Research
state: Florida
city: Duncansville
country: United States
facility: Altoona Center for Research
state: Pennsylvania
Study officials:
References: