A Study of TJ003234 in Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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Study Purpose and Design: A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Dose and Multiple Ascending Doses of TJ003234 in Rheumatoid Arthritis Patients.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Dose and Multiple Ascending Doses of TJ003234 in Rheumatoid Arthritis Patients

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: TJ003234 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be ≥ 18 and ≤70 years old when signing the informed consent, with no limitation of gender. Established Rheumatoid arthritis patients, diagnosed by ACR/EULAR criteria 2010 at least 6 months prior to randomisation. Single Ascending Dose: DAS28 score≤3.2. Multiple Ascending Dose: DAS28 score≤5.1 and >3.2. Allowed one or more standard treatments, but the start date should no later than 12 weeks(84 days) before the randomisation and should take at a stable dose more than 4 weeks(28 days) before the randomisation. The combination taken of Methotrexate (MTX) and leflunomide was not allowed within 4 weeks (28 days) before randomization. Subjects must agree to attendance the study and signed the inform concent by themselves. Subjects(include subjects's wife) are no pregnancy plan during the sceering and 3 months after complete the study and agree to use contraceptives that protocol suggest. Exclusion Criteria: Employees of the hospital or any other person that paticipant in the study and their immedidte family members. A documented history of an autoimmune disease other than RA (other than secondary Sjögren's syndrome) . Previous received Any biologic DMARD therapy including tsDMARD. •A positive hepatitis B (HBsAg, anti-HBc, and/or IgM anti-HBc), hepatitis C or HIV test at screening, indicative of a current or past infection. A history of active tuberculosis (TB) or positive serological test for TB (Quantiferon TB Gold or T-SPOT). Female patients who are pregnant during the study, or are breastfeeding. •Malignancy, or prior malignancy, with a disease free interval of <5 years after diagnosis and intervention except curative treatment for basal and squamous cell skin cancer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-blind, Placebo-controlled
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TJ003234<br>Intravenous administration, single dose (0.3-1-3-10mg/kg) or multiple dose (1-3-6mg/kg, once every week, for 8 weeks) Mode of administration: The investigational drug is administered by intravenous infusion | Biological: TJ003234 injection<br>* Intravenous administration, single dose (0.3-1-3-10mg/kg) or multiple dose (1-3-6mg/kg, once every week, for 8 weeks)<br>|
| Placebo Comparator: Placebo<br>Intravenous administration, single dose (0.3-1-3-10mg/kg) or multiple dose (1-3-6mg/kg, once every week, for 8 weeks) Mode of administration: The investigational drug is administered by intravenous infusion | Biological: TJ003234 injection<br>* Intravenous administration, single dose (0.3-1-3-10mg/kg) or multiple dose (1-3-6mg/kg, once every week, for 8 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subject with adverse events(AEs) | Number of subject with adverse events(AEs) to evaluate satety in patient with RA with vital signs, Electrocardiograms, physical examinations, laboratory tests and respiratory-related examinations | First dose up to last follow-up visit (i.e. 90 days after dosing for single dose part, 140 days after first dose for multiple dose part) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC from time 0 to the time of the last quantifiable concentration AUC0-tlast of TJ003234 | AUC from time 0 to the time of the last quantifiable concentration AUC0-tlast of TJ003234 | Day1 to 90 days after dosing for single dose part, 140 days after for multiple dose part | 
| Maximum observed plasma concentration (Cmax) of TJ003234 | Maximum observed plasma concentration (Cmax) of TJ003234 | Day1 to 90 days after dosing for single dose part, 140 days after for multiple dose part | 
| The proportion of subjects who produce anti-drug antibodies | The proportion of subjects who produce anti-drug antibodies | Day1 to 90 days after dosing for single dose part, 140 days after for multiple dose part | 
| The proportion of subjects who produce neutralizing antibodies | The proportion of subjects who produce neutralizing antibodies | Day1 to 90 days after dosing for single dose part, 140 days after for multiple dose part | 
| The proportion of subjects who produce the titers of anti-drug antibodies and neutralizing antibodies | The proportion of subjects who produce the titers of anti-drug antibodies and neutralizing antibodies | Day1 to 90 days after dosing for single dose part, 140 days after for multiple dose part | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, biologics