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The goal of this clinical trial is to evaluate the tolerability, pharmacokinetics and pharmacodynamics of Proximod in healthy subjects and patients with rheumatoid arthritis. The main questions it arms to answer are:
Participants will receive test tablets or placebo at the indicated date and collect blood samples.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo, qd, oral administration for 28 days |
|
| Proximod | Experimental | Proximod Tablets, 5mg, qd, oral administration for 28 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Proximod | Drug | Multiple-dose to establish the safety and PK profile in both healthy subjects and patients with rheumatoid arthritis |
|
| Measure | Description | Time Frame |
|---|---|---|
| Peak plasma concentration (Cmax) | Up to 48 days | |
| Time to peak plasma concentration (Tmax) | Up to 48 days | |
| The lowest plasma concentration (Cmin) | Up to 48 days | |
| Half-life (t1/2) | Up to 48 days | |
| Area under the plasma concentration versus time curve (AUC) | Up to 48 days | |
| Number of adverse events and number of participants with adverse events | Up to 48 days |
| Measure | Description | Time Frame |
|---|---|---|
| Lymphocyte count | Up to 48 days | |
| Percentage of CD3+CD4+ and CD3+CD8+T cells | Up to 48 days | |
| ACR20 score in Patients With Rheumatoid Arthritis |
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Inclusion Criteria for healthy subjects:
Exclusion Criteria for healthy subjects:
Inclusion Criteria for patients with rheumatoid arthritis:
Exclusion Criteria for patients with rheumatoid arthritis:
AST or ALT>1.5 times ULN Total bilirubin>2 times ULN Hemoglobin (male) <10.0g/dL (100.0g/L), or (female) <9.0g/dL (90.0g/L) Total white blood cell count <3.0×109/L Neutrophil count <1.0×109/L Creatinine clearance rate (CLcr) ≤50 mL/min Any clinically significant laboratory abnormal values that the researcher believes may interfere with the evaluation of the results of this study.
Those with any systemic inflammatory disease except RA. People with Felty syndrome. Decompensated heart failure (New York Heart Association classification III and IV), unstable angina, stroke or transient ischemic attack, myocardial infarction, persistent and Clinically significant arrhythmias, coronary artery bypass grafting, or percutaneous coronary intervention.
Have a history of lymphoproliferative disease, or have various signs or symptoms that may be lymphoproliferative disease, including lymphadenopathy or splenomegaly, or have experienced treated or untreated malignant tumors, whether localized or not Evidence of recurrence or metastasis.
The subject has any active malignant tumor or history of malignant tumor within 5 years before the screening visit, except for cutaneous squamous or basal cell carcinoma, cervical carcinoma in situ, or breast ductal carcinoma in situ that has been treated and considered cured .
Suffer from genetic immunodeficiency or have a family history of hereditary immunodeficiency.
Those who have a history of uveitis and are not suitable to participate in the trial as considered by the researcher.
Those who have undergone joint surgery within 6 months before the first dose of the trial.
Those who have severe infection within 3 months before screening or acute infection symptoms within 7 days before screening are judged by the researcher to be unsuitable participants.
Those who have a history of herpes zoster or chickenpox. Those who have a history of drug abuse or have used drugs within the past five years.
Have cardiovascular, respiratory system, liver, kidney, digestive tract, immune, blood, endocrine, metabolic, psychiatric and neurological diseases or history, which may affect the absorption, distribution, metabolism and excretion of the drug or interfere with the results according to the researcher's judgment evaluator.
10. Use of any of the following drugs or treatments: Received intra-articular, intramuscular injection, intravenous injection, trigger point or tender point, intracapsular, or intratendinous glucocorticoid treatment within 8 weeks before the first dose.
Those who have used any non-steroidal anti-inflammatory drugs (NSAIDs) or oral corticosteroids within 1 week before the first dose of the trial.
Received iguratimod or interferon treatment (such as Lusperin, Ganlenon, Rebetron, etc.) within 1 month before the first dose.
Those who have received any live vaccine, attenuated vaccine or inactivated vaccine within 1 month before the first dose (for example, those who have received the new coronavirus vaccine need to wait 4 weeks or more after completing the last dose before they can be enrolled).
Have used other drugs known to have strong immunosuppressive or immunomodulatory effects (such as Pavlin, Tripterygium wilfordii, Mycophenolate mofetil, Cyclospora) within 4 weeks before the first dose. (e.g., tacrolimus, azathioprine, 6-mercaptopurine, etc.).
Those who have used any other prescription drugs, over-the-counter drugs, Chinese herbal medicines, food or food supplements that may have an impact on the test drug, such as CYP3A4 inhibitors or inducers, within 2 weeks before the first dose of the trial. , grapefruit juice, etc.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The first hospital of Jilin University | Changchun | Jilin | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39454617 | Derived | Zhang H, Li Q, Li C, Wu M, Chen H, Li Y, You F, Zhao Y, Jin J, Chen X, Ding Y. Evaluation of proximod, a selective agonist of sphingosine-1-phosphate receptor-1, in healthy volunteers and patients with rheumatoid arthritis: a phase 1, double-blind, randomised, placebo-controlled, ascending dose trial. Lancet Rheumatol. 2024 Dec;6(12):e837-e847. doi: 10.1016/S2665-9913(24)00199-1. Epub 2024 Oct 22. |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| Placebo | Drug | Placebo controlled |
|
| Day 8, 15, 22, 29 and 48 compared to baseline |
| Disease Activity Score(DAS28-CRP)in Patients With Rheumatoid Arthritis | Day 8, 15, 22, 29 and 48 compared to baseline |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |