A Study of the Pharmacokinetics and Safety of SM03 in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This was an open phase I trial to evaluate the pharmacokinetic, pharmacodynamic, safety and clinical activity profiles of anti-CD22 monoclonal antibody SM03 in patients with active RA.

Detailed Description
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This was an open phase I trial to evaluate the PK, PD, safety,tolerability, efficacy, and immunogenicity of SM03 in patients with RA. The total study duration was approximately 16 weeks for each participant, including a screening period of maximally 4 weeks, a multiple-dose period of 2 weeks (day 0   day 14), and a post-treatment follow-up period of 10 weeks (day 15   day 84).

Official Title
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An Open-label, Multiple-dose Study to Assess the Pharmacokinetics, Pharmacodynamics, Preliminary Clinical Activity and Safety of Human Mouse Chimeric Anti-CD22 Monoclonal Antibody (SM03) in Patients With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Biological: SM03


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rheumatoid arthritis (RA) for ≥ 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis. Moderate to severe active RA with swollen joint count (SJC) ≥ 6 (66 joint count), and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline. At screening, either C-reactive protein (CRP) ≥ 0.6 mg/dL (6 mg/L), or Erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour, or Morning stiffness of joint for ≥ 45 minutes. Receiving methotrexate (MTX) 7.5 - 25mg/week (oral) for at least 12 weeks, at a stable dose over the past 4 weeks. Exclusion Criteria: Females who are pregnant, breastfeeding, or planning a pregnancy during the Treatment Period of and 12 months after the last infusion of study drug. Rheumatic autoimmune disease other than RA. Use of any biological DMARDs for RA within past 6 months. Active infection, or history of serious or chronic infection. Any significant cardiac disease, moderate to severe chronic obstructive pulmonary disease. Allergy or sensitivity to components of the drug vial or any of the materials used for infusion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biological: SM03<br>Biological: SM03 600 mg or 900 mg intravenous (IV) on week 0 , 2. | Drug: Biological: SM03<br>* Biological: SM03 600 mg or 900 mg intravenous (IV) on week 0,2<br>* Other names: SM03;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration Time Cure(AUC0-t) | Pharmacokinetic endpoint: Area Under the Concentration Time Cure(AUC0-t) | Week 0 to 12 | 
| Time to Maximum Plasma Concentration (Tmax) | Pharmacokinetic endpoint: Time to Maximum Plasma Concentration (Tmax) | Week 0,2 | 
| Peak Plasma Concentration (Cmax) | Pharmacokinetic endpoint: Peak Plasma Concentration (Cmax) | Week 0, 2 | 
| Systemic Clearance (CL) | Pharmacokinetic endpoint: Systemic Clearance (CL) | Week 0 to 12 | 
| Terminal Half-life (T1/2) | Pharmacokinetic endpoint:Terminal Half-life (T1/2) | Week 0 to 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced at Least One Adverse Event | An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure. | Week 0 to 12 | 
| Number of ACR20, ACR50, and ACR70 Responders at Week 12 | American College of Rheumatology (ACR) Responder Index is based on a set of evaluations: the Investigator Tender Joint Count/Number of Tender Joints (out of 68 Joints); Investigator Swollen Joint Count/Number of Swollen Joints (out of 66 Joints); Patient Global Assessment of Disease Activity (PGAD); Investigator Global Assessment of Disease Activity (IGAD); Patient Global Assessment of Pain (PGAP); Health Assessment Questionnaire Disability Index (HAQ-DI); and ESR. ACR response indicates percent change (ie, improvement) from baseline (20%, 50%, 70%) PGAD & IGAD | Week 2,4,8,12 | 
| Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 12 | The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: The number of swollen and tender joints assessed using the 28-joint count; Erythrocyte sedimentation rate (ESR); Patient's global assessment of disease activity measured on a 10 cm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6. | Week 0,2,4,8,12 |