A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-56022473 in Subjects With Systemic Lupus Erythematosus

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and tolerability of JNJ-56022473 following multiple subcutaneous (SC) study agent administrations in subjects with Systemic Lupus Erythematosus (SLE) and to determine whether premedication with corticosteroids is required to improve the tolerability of SC JNJ-56022473.

Official Title
-----------------
A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-56022473 in Subjects With Systemic Lupus Erythematosus

Conditions
-----------------
Lupus Erythematosus, Systemic

Intervention / Treatment
-----------------
* Drug: JNJ-56022473
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must have a body weight in the range of 40 to 100 kilogram (kg), inclusive, and have a body mass index (BMI) of 18 to 32 kilogram per meter square (kg/m^2), inclusive, at screening Subjects eligible for enrollment in this study must qualify as follows: a) must meet Systemic Lupus International Collaborating Clinics (SLICC) criteria for diagnosis of lupus and b) must have at least one non-serologic clinical activity defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) within 3 months prior to first study agent administration Have a positive gene signature score during screening, prior to first administration of study agent Subjects using allowed pre-existing lupus treatments, if stable for at least 6 weeks prior to the first dose of study medication: oral corticosteroids equivalent to an average dose up to or equal to (<=) 10 milligram (mg) of prednisone/day use of antimalarials (such as chloroquine or hydroxychloroguine) for at least 8 weeks maximum of 1 non-corticosteroid immunosuppressive drug Exclusion Criteria: Subject with history or suspected occurrence of drug-induced systemic lupus erythematosus (SLE) Subject has unstable lupus nephritis and/ or has active Central nervous system (CNS) lupus or history of severe CNS lupus, including but not limited to seizures, psychosis, transverse myelitis, CNS vasculitis and optic neuritis Major surgery prior to, and, if planned, during and shortly after the study is not eligible Subject has or has had an acute illness, including a common cold, within 2 weeks prior to the study agent administration or has had a major illness or hospitalization within 4 months prior to the screening visit Any other inflammatory diseases that might confound the evaluations of efficacy are excluded

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: JNJ-56022473 or Placebo (4:1)<br>Subjects will receive 3 subcutaneous (SC) administrations of the same dose level of JNJ-56022473 Dose 1, Dose 2, or Dose 3 or placebo every 2 weeks (in the ratio of 4:1 [4 active: 1 placebo]). | Drug: JNJ-56022473<br>* Subjects will be administered with JNJ-56022473 SC depending upon on the dose levels.<br>Drug: Placebo<br>* Subjects will receive matching placebo.<br>|
| Experimental: Part B: JNJ-56022473 or Placebo (5:1)<br>Subjects will receive 3 SC administrations of the same dose level of JNJ-56022473 or placebo every 2 weeks (in the ratio of 5:1 [5 active: 1 placebo]). The dose level(s) will be based upon an interim analysis (IA) of the Part A data. | Drug: JNJ-56022473<br>* Subjects will be administered with JNJ-56022473 SC depending upon on the dose levels.<br>Drug: Placebo<br>* Subjects will receive matching placebo.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) by Severity and Serious Adverse Events (SAEs) Through Week 16 |  | Up to 16 weeks | 
| Percentage of Subjects With Grade 1, Grade 2, and Grade 3 Systemic Administration-Related Reactions (SARR) After Drug Administration |  | Up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration of JNJ-56022473 |  | Up to 16 weeks | 
| Number of Subjects With Presence of Anti-JNJ-56022473 Antibodies |  | Up to 16 weeks | 
| Gene Expression Measured in Whole Blood by Quantitative Polymerase Chain Reaction (qPCR) | Whole blood samples collected from subjects enrolled in this study will be examined by qPCR to assess the ability of JNJ-56022473 to initiate the expected effect on target cells. | Up to 38 weeks | 
| Counts of Target Cells | Counts of target cells will be measured by flow cytometry from whole blood. | Up to 38 weeks |