Rheumatoid Arthritis
Conditions
Brief summary
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
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).
Interventions
DRUGBiological: SM03
Biological: SM03 600 mg or 900 mg intravenous (IV) on week 0,2
Sponsors
SinoMab BioScience Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Half-life (T1/2) | Week 0 to 12 | Pharmacokinetic endpoint:Terminal Half-life (T1/2) |
| Area Under the Concentration Time Cure(AUC0-t) | Week 0 to 12 | Pharmacokinetic endpoint: Area Under the Concentration Time Cure(AUC0-t) |
| Time to Maximum Plasma Concentration (Tmax) | Week 0,2 | Pharmacokinetic endpoint: Time to Maximum Plasma Concentration (Tmax) |
| Peak Plasma Concentration (Cmax) | Week 0, 2 | Pharmacokinetic endpoint: Peak Plasma Concentration (Cmax) |
| Systemic Clearance (CL) | Week 0 to 12 | Pharmacokinetic endpoint: Systemic Clearance (CL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event | Week 0 to 12 | 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. |
| Number of ACR20, ACR50, and ACR70 Responders at Week 12 | Week 2,4,8,12 | 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 |
| Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 12 | Week 0,2,4,8,12 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Positive for Anti-Drug Antibody (ADA) | Week 0,4,8,12 | Serum ADA positivity is determined over course of the trial duration |
| Change From Baseline in CD19+ B-cell Count During the Study Period | Week 0,4,8,12 | Pharmacodynamic endpoint: change from baseline in CD19+ B-cell count during the study period |
Countries
China
Outcome results
None listed