Tolerance, Pharmacokinetics and Preliminary Efficacy of T0001 in RA (Rheumatoid Arthritis)

An Open, Dose Escalation, Multiple Dose Study to Assess Tolerance、Pharmacokinetics、Preliminary Efficacy of T0001 in RA (Rheumatoid Arthritis)

The purpose of this study is to assess the MTD, Pharmacokinetics and preliminary efficacy of T0001 in Rheumatoid Arthritis.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: T0001; Drug: T0001; Drug: T0001; Drug: T0001; Drug: Enbrel

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-45 years old;
• Diagnosed with active RA;
• DMARDs therapy must not be used for at least 28 days prior to baseline;
• If a patient has received NSAIDs，current NSAIDs therapy must have been at a stable dose for at least 28 days prior to baseline;
• Patient or patient's legal representative able to give written informed consent for participation in the trial.

Exclusion Criteria:

• Acute or chronic infection, or history of active tuberculosis;
• History of diseases of central nervous system, cardiovascular system, kidney, liver ( specified liver function index), digestive system, respiratory system , metabolism system;
• Patients who have a high risk of infection (with a current infectious disease, a chronic infectious disease, a history of serious infectious disease);
• Patients who use 5 Unit doses tuberculin skin test are positive( 48-72 hour scleroma reading≥5mm);
• Patients who currently have, or who have a history of, malignancy;
• Patients who lack of understanding ,communication or collaboration, and can't comply with the protocols;
• Female patients who are breastfeeding or pregnant, who are of childbearing potential.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T0001	Drug: T0001; injection (SC) T0001 15mg weekly for 12 weeks; Drug: T0001; injection (SC) T0001 30mg weekly for 12 weeks; Drug: T0001; injection (SC) T0001 30mg every two weeks for 12 weeks; Drug: T0001; injection (SC) T0001 50mg every two weeks for 12 weeks
Active Comparator: Enbrel	Drug: Enbrel; injection (SC) enbrel 50mg twice a week for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerance Dose	4 weeks
Peak Plasma Concentration (Cmax)	14 weeks
Area under the plasma concentration versus time curve (AUC)	14 weeks
steady-state concentration（Css）	14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
American College of Rheumatology 20% (ACR20) Response	ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)	12 weeks
American College of Rheumatology 50% (ACR50) Response	ACR50 responders are subjects with at least 50% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)	12 weeks
American College of Rheumatology 70% (ACR70) Response	ACR70 responders are subjects with at least 70% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)	12 weeks

Collaborators and Investigators

• Sponsor: Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.
• Investigators: Study Director: wang wei, Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.; Principal Investigator: Li zhan Guo, Ph.D, Peking University People's Hospital

Publications and helpful links

General Publications

• Shen Y, Li G, Gu C, Chen B, Chen A, Li H, Gao B, Liang C, Wu J, Yang T, Jin L, Su Y. T0001, a variant of TNFR2-Fc fusion protein, exhibits improved Fc effector functions through increased binding to membrane-bound TNFalpha. PLoS One. 2017 May 19;12(5):e0177891. doi: 10.1371/journal.pone.0177891. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2015
• Primary Completion (Actual): November 6, 2017
• Study Completion (Actual): November 6, 2017

Study Registration Dates

• First Submitted: June 18, 2015
• First Submitted That Met QC Criteria: June 22, 2015
• First Posted (Estimate): June 25, 2015

Study Record Updates

• Last Update Posted (Actual): July 8, 2019
• Last Update Submitted That Met QC Criteria: July 5, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Antirheumatic Agents; Immunologic Factors; T0001; Immunoglobulin Fc Fragments
• Other Study ID Numbers: T0001-P2.0