RC18 in Patients With Relapsing Remitting Multiple Sclerosis：a Phase II Trial

Study Overview
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Brief Summary
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To observe the safety and effectivity of a Recombinant Human B Lymphocyte Stimulator Receptor : Immunoglobulin G( IgG ) Fc Fusion Protein for injection (RC18) in patients with relapsing remitting multiple sclerosis, analyze the dose-response relationship and provide a dose basis for follow-up clinical trials.

Official Title
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RC18, a Recombinant Human B Lymphocyte Stimulator Receptor:Immunoglobulin G( IgG ) Fc Fusion Protein for Injection in Patients With Relapsing Remitting Multiple Sclerosis：a Phase II Trial

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Biological: RC18 160mg
* Biological: RC18 240mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsing remitting multiple sclerosis meet the diagnostic criteria of McDonald 2017. 18-55 years old, male or female At least 2 recurrences (including clinical recurrence and imaging recurrence) were recorded within 1 year before randomization. Gadolinium enhanced T1 lesions (≥ 1) in the brain at the screening stage EDSS score ≤ 5.5 Informed consent signed voluntarily Exclusion Criteria: Patients with multiple sclerosis over 5 years Those who are unable to perform MRI or who are allergic to gadolinium contrast agent during the test In addition to multiple sclerosis, patients with chronic active immune system disease or stable condition but requiring immunotherapy (glucocorticoids and / or immunosuppressants) (such as rheumatoid arthritis, scleroderma, Sjogren's syndrome, Crohn's disease, ulcerative colitis, etc.) or known immune deficiency syndrome (AIDS, genetic immune deficiency and drug-induced immunity) Patients who used glucocorticoid maintenance therapy before randomization could participate in the trial after discontinuation of the drug Patients with Aquaporin 4 (AQP4) antibody positive and / or Myelin oligodendrocyte glycoprotein(MOG) antibody positive within 1 year before randomization Patients who have received the following treatment: Interferon, pegylated interferon, galatirel acetate, dimethyl fumarate were used within 4 weeks before randomization. Fengomod, IV immunoglobulin or plasma exchange within 12 weeks before randomization. Alemtuzumab, daclizumab and ocrelizumab were used within 24 weeks before randomization. Before randomization, azathioprine (AZA, half-life t1/2 = 6hrs), mycophenolate mofetil (t1/2 = 16hrs), leflunomide (LEF, t1/2 = 14.7hrs), tacrolimus (t1/2 = 43hrs), teriflunomide (t1/2 = 18 days), cyclosporin, In addition to leflunomide and telifluoramine, immunosuppressants such as CSA, t1/2 = 27 hrs, methotrexate (MTX, t1/2 = 14 HRS), cyclophosphamide (CTX, t1/2 = 6 hrs) can be added to the group after the interval of withdrawal is more than 5 times of half-life. Leflunomide and tertiazem need to be eluted with coleridine. The drug can be stopped and the following measures can be taken: Take 8 g of coleridine three times a day for 11 days. If the dose of 8 g can not be tolerated, it can be changed to 4 g each time. The time and times are the same as before. Cladribine or mitoxantrone was used within 1 year before randomization. Lymphoid irradiation and bone marrow transplantation were received before randomization. Patients were participated in any clinical trial 28 days before randomization or within 5 times half-life of study drug participating in clinical trial (whichever is longer). Patients with any persistent or chronic active infection or serious infection history in the screening period, such as shingles; active tuberculosis (patients with latent tuberculosis can participate in the test if they are given isoniazid and / or rifampin at the same time); HIV infection; syphilis antibody positive; HCV antibody positive; HBsAg positive; HBsAg negative but HBcAb positive, the HBV-DNA quantitative test is needed. If the HBV-DNA is positive, the patient should be excluded. If the HBV-DNA is negative, the patient can not be excluded. The results of abnormal laboratory tests to be excluded include but are not limited to: Leukocyte count < 3 × 10 9 / L; neutrophil < 1.5 × 10 9 / L; hemoglobin < 85g / L; platelet count < 80 × 10 9 / L; serum creatinine > 1.5 × ULN, accompanied by creatinine clearance < 50ml / min (measured value, or calculated by Cockcroft Gault formula); total bilirubin > 1.5 × ULN; ALT > 3 × ULN; AST > 3 × ULN; alkaline phosphatase > 2 × ULN; IgG < lower limit of normal value; IgM < lower limit of normal value; Cancer patients Pregnant women, lactating women and patients with family planning during the trial Patients with other mental disorders Patients who experienced any of the following events within 12 weeks before randomization: myocardial infarction, unstable ischemic heart disease, stroke, or NYHA class IV heart failure The researchers believe that the patients are compliant insufficiently or not suitable to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RC18 160mg<br>RC18 160mg is injected subcutaneously once a week for 48 times. | Biological: RC18 160mg<br>* RC18 160mg is injected subcutaneously once a week for 48 times.<br>* Other names: telitacicept;|
| Experimental: RC18 240mg<br>RC18 240mg is injected subcutaneously once a week for 48 times. | Biological: RC18 240mg<br>* RC18 240mg is injected subcutaneously once a week for 48 times.<br>* Other names: telitacicept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number changes of gadolinium enhanced T1 lesions in the brain | Number changes of gadolinium enhanced T1 lesions in the brain at 12, 24, 36, and 48 weeks compared with baseline | At 12, 24, 36, and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume changes of gadolinium enhanced T1 lesions | Volume changes of gadolinium enhanced T1 lesions at 12, 24, 36 and 48 weeks compared with baseline | At 12, 24, 36 and 48 weeks | 
| Number changes of new low signal T1 lesions | Number changes of new low signal T1 lesions at week 12, 24, 36, and 48 weeks compared with baseline | At week 12, 24, 36, and 48 weeks | 
| Number changes of new / increased T2 lesions in the brain | Number changes of new / increased T2 lesions in the brain at 12, 24, 36 and 48 weeks compared with baseline | At 12, 24, 36 and 48 weeks | 
| Volume changes of T2 lesions in brain | Volume changes of T2 lesions in brain at 12, 24, 36 and 48 weeks compared with baseline | At 12, 24, 36 and 48 weeks | 
| Proportion of patients who did not recur | Proportion of patients who did not recur between 0 and 48 weeks | Between 0 and 48 weeks | 
| Recurrence rate | Annual recurrence rate | 0-48weeks |