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

Phase 1

Completed

• Conditions: Rheumatoid Arthritis

• Registration Number: NCT04704492
• Lead Sponsor: SinoMab BioScience Ltd

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).

Study Timeline

• Study Start: 2012-08-14
• Primary Completion: 2013-12-16
• Study Completion: 2013-12-16
• Status Verified: 2021-01
• Study First Submitted: 2021-01-06
• Study First Submitted QC: 2021-01-08
• Last Update Submitted: 2021-01-08
• Study First Posted: 2021-01-11
• Last Update Posted: 2021-01-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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.
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.
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

Trial Locations

Locations (1)

Clinical Pharmacology Research Center & Translational Medicine Centre, Peking Union Medical College Hospital; 🇨🇳 Beijing, China