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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04704492
• Other study ID #: SM03-RA(I/II)-1.0
• Secondary ID: CTR20131127
• Status: Completed
• Phase: Phase 1
• Start date: August 14, 2012
• Est. completion date: December 16, 2013

Study information

• Verified date: January 2021
• Source: SinoMab Pty Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 16, 2013
• Est. primary completion date: December 16, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Biological: SM03
Biological: SM03 600 mg or 900 mg intravenous (IV) on week 0,2

Locations

Country	Name	City	State
China	Clinical Pharmacology Research Center & Translational Medicine Centre, Peking Union Medical College Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
SinoMab Pty Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants Positive for Anti-Drug Antibody (ADA)	Serum ADA positivity is determined over course of the trial duration	Week 0,4,8,12
Other	Change From Baseline in CD19+ B-cell Count During the Study Period	Pharmacodynamic endpoint: change from baseline in CD19+ B-cell count during the study period	Week 0,4,8,12
Primary	Area Under the Concentration Time Cure(AUC0-t)	Pharmacokinetic endpoint: Area Under the Concentration Time Cure(AUC0-t)	Week 0 to 12
Primary	Time to Maximum Plasma Concentration (Tmax)	Pharmacokinetic endpoint: Time to Maximum Plasma Concentration (Tmax)	Week 0,2
Primary	Peak Plasma Concentration (Cmax)	Pharmacokinetic endpoint: Peak Plasma Concentration (Cmax)	Week 0, 2
Primary	Systemic Clearance (CL)	Pharmacokinetic endpoint: Systemic Clearance (CL)	Week 0 to 12
Primary	Terminal Half-life (T1/2)	Pharmacokinetic endpoint:Terminal Half-life (T1/2)	Week 0 to 12
Secondary	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
Secondary	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
Secondary	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