Efficacy and Safety Study of KN019 in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the efficacy, pharmacokinetics, safety, and immunogenicity of KN019 after intravenous administration on background methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate.

Detailed Description
-----------------
This study is designed to provide efficacy data in support of the proposed claims of reducing signs and symptoms, improvement in physical function, and 1 year safety data for KN019 dosed at 5 and 10 mg/kg in patients with inadequate response to stable weekly doses of background methotrexate.

Official Title
-----------------
A Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of KN019 in Patients With Active Rheumatoid Arthritis While Receiving Methotrexate

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Biological: KN019, 5mg/kg
* Biological: KN019, 10 mg/kg
* Biological: Placebo
* Combination Product: Methotrexate


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: The patient must meet the American College of Rheumatology (ACR) classification criteria for the diagnosis of rheumatoid arthritis (RA) by satisfying at least four of the seven criteria; Patients must have been taking methotrexate for at least 3 months with at least a weekly dose of 7.5-25 mg, and a stable dose for 28 days prior to treatment (Day 1) The patient must have active disease at both screening and baseline, as defined by having both: 6 tender/painful joints on motion (out of 68 joints assessed); and; 6 swollen joints (out of 66 joints assessed); CRP ≥ 7 mg/L, or ESR ≥28 mm/h Key Exclusion Criteria: Pregnant or lactating females. History of any other autoimmune rheumatic disease. Patients who have previously received CTLA4-Ig therapy for any reason.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KN019 5mg/kg<br>Intravenous (IV) solution, 5 mg/kg, Day 1, Day 15, Day 29; every 28 days thereafter, 12 months | Biological: KN019, 5mg/kg<br>* Solution, intravenous, 5 mg/kg<br>Combination Product: Methotrexate<br>* Tablets, oral, 7.5-25 mg weekly to be adjusted according to patient condition<br>|
| Experimental: KN019 10mg/kg<br>Intravenous (IV) solution, 10 mg/kg, Day 1, Day 15, Day 29; every 28 days thereafter, 12 months | Biological: KN019, 10 mg/kg<br>* Solution, intravenous, 10 mg/kg<br>Combination Product: Methotrexate<br>* Tablets, oral, 7.5-25 mg weekly to be adjusted according to patient condition<br>|
| Placebo Comparator: Placebo<br>Intravenous (IV) solution, Day 1, Day 15, Day 29; every 28 days thereafter, 12 months | Biological: Placebo<br>* Solution, intravenous, Placebo<br>Combination Product: Methotrexate<br>* Tablets, oral, 7.5-25 mg weekly to be adjusted according to patient condition<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants the proportion of subjects meeting the American College of Rheumatology criteria for 20% improvement (ACR 20) on Day 169 | The ACR 20 is based on 20% improvement (compared with baseline values) in tender and swollen joint counts and on 20% improvement in 3 of the remaining 5 core set measures (participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function) and 1 acute phase reactant value. | At Day 169 |