A Multi-center, Randomized, Double-blind Phase Ib Clinical Study to Evaluate the Safety, Tolerability, PK/PD Characteristics and Preliminary Efficacy of IL-6R mAb Injection in Patients With Active Moderate-to-Severe Rheumatoid Arthritis.

Beijing VDJBio Co., LTD.5 sites in 1 country40 target enrollmentMarch 2, 2021

ConditionsRheumatoid Arthritis

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Rheumatoid Arthritis
Sponsor: Beijing VDJBio Co., LTD.
Enrollment: 40
Locations: 5
Primary Endpoint: Maximum observed plasma concentration (Cmax)
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-dose,multi-center, randomized, double-blind, positive-controlled and parallel group clinical study that aims to evaluate the safety,tolerability,PK/PD characteristics and Preliminary Efficacy of Recombinant Humanized IL-6R Monoclonal Antibody Injection in Patients With Active Moderate-to-Severe Rheumatoid Arthritis.

Detailed Description

This study is aim to evaluate the safety, tolerability, PK/PD characteristics, immunogenicity parameters and Preliminary Efficacy of Recombinant Humanized IL-6R Monoclonal Antibody Injection in Patients With Active Moderate-to-Severe Rheumatoid Arthritis. There are 4 dose groups and each group enrolls 10 patients: 4mg/kg(IL-6R mAb); 6mg/kg(IL-6R mAb); 8mg/kg(IL-6R mAb) and 8mg/kg(tocilizumab ).each patient receives a single intravenous(i.v.) dose. The infusion time is from 60 to 90 minutes (the speed can be adjusted appropriately if there are injection reactions).

Registry

clinicaltrials.gov

Start Date

March 2, 2021

End Date

February 25, 2022

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Beijing VDJBio Co., LTD.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age at the time of screening is 18\~70 years old (including boundary value), gender is not limited;
•According to the standards revised by the American College of Rheumatology (ACR) in 1987, or the American College of Rheumatology/Europe Anti-Rheumatism Alliance (ACR/EULAR) 2010 classification criteria, patients diagnosed with adult RA and The history of RA is at least 6 months;
•Patients with moderate to severe active RA at screening and baseline visit, defined as having at least 6/68 joints Tenderness or pain and swelling of at least 6/66 joints during exercise After major surgical treatment, for the screening of this study, joint tenderness count (TJC) and closed The joint swelling count (SJC) evaluation, this joint cannot be counted);
•Erythrocyte sedimentation rate (ESR) ≥28mm/hour, or C-reactive protein ≥ 10mg/L;
•Before screening, due to lack of efficacy or intolerance, poor response to MTX treatment;
•Have received and tolerated at least 7.5mg/week MTX treatment for at least 12 weeks before screening, and within 4 weeks before screening The dose of MTX is stable within the range of ≥7.5mg/week and ≤20mg/week. This MTX dose is expected to remain stable during the study period It will only be adjusted for safety reasons;
•If subjects are using non-steroidal anti-inflammatory drugs (NSAIDs) or other analgesics to treat RA, they must be stable before enrollment.
•Fixed-dose treatment for at least 2 weeks;
•If the subject takes glucocorticoids orally, the dose must be stabilized at least 4 weeks before enrollment to be equivalent to ≤10mg Prednisone/day dose;
•Subjects who receive non-disabled concomitant drug treatment for any reason must always be on a stable treatment plan, definition It is that no new drug has been taken or the dosage has been changed within 7 days or 5 half-lives (whichever is longer) before screening;

Exclusion Criteria

•Have used DMARDs other than MTX (including sulfasalazine, antimalarial drugs, penicillamine, Azathioprine, cyclosporine A, cyclophosphamide, etc.), botanical drugs (including tripterygium wilfordii, total glucosides of paeony, sinomenine, etc.), and Those who have received any viral vaccine (such as influenza vaccine) immunotherapy;
•Those who have had major trauma or undergone major surgery within 4 weeks before screening, or plan to receive medical treatment within 2 months after randomization.
•Those who have undergone major surgery;
•Those who have used intra-articular, intramuscular or intravenous corticosteroids within 6 weeks before screening;
•Anuranofin, gold glucosinolate (gold for injection), gold thiomalate (gold for injection) have been used within 8 weeks before screening Or those immunized with oral polio vaccine;
•Those who received flunomide treatment within 12 weeks before screening (if receiving standard cholestyramine elution treatment 4 weeks before screening) (Cholestyramine 8g orally, 3 times a day for 11 consecutive days), then the subject can be included\];
•Those who have intravenous injection of gamma globulin, plasma exchange or use prosorba column within 24 weeks before screening;
•Anakinra and Etanercept were used within 4 weeks before screening; Adalimumab and Etanercept were used within 8 weeks before screening Fliximab; Golimumab and Certuzumab used within 10 weeks before screening; Abba within 12 weeks before screening Cipro; used denosumab within 21 weeks before screening; used rituximab within 26 weeks before screening;
•Those who have used tocilizumab in the past;
•Uncontrolled cardiovascular system, respiratory system, digestive system, endocrine system, blood as judged by the investigator System, nervous system or psychiatric disorder or any other serious and/or unstable disease or medical history, and the investigator agrees For these diseases or medical history, taking study drugs may bring risks or interfere with the interpretation of data;

Outcomes

Primary Outcomes

Maximum observed plasma concentration (Cmax)

Time Frame: First dose up to last follow-up visit（Day1-Day57）

Maximum observed plasma concentration (Cmax) of IL-6R

AUC from time 0 to the time of the last quantifiable concentration AUC0-tlast of IL-6R

Time Frame: First dose up to last follow-up visit（Day1-Day57）

AUC from time 0 to the time of the last quantifiable concentration AUC0-tlast of IL-6R

Safety as measured by patients with adverse events

Time Frame: First dose up to last follow-up visit(Day1-Day57)

The number of occurrences and incidence are calculated

Secondary Outcomes

HAQ- DI(At the 4th and 8th week of medication)
Analysis of immunogenicity(From Day15-Day71 after administration)
ACR20 ACR 50 ACR 70 response rate(At the 4th and 8th week of medication)
FACIT-F(At the 4th and 8th week of medication)
Clinical Disease Activity Index (CDAI) response rate(At the 4th and 8th week of medication)