A Safety and Tolerability Study of MEDI-570 in Systemic Lupus Erythematosus

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and tolerability of MEDI-570 in adult subjects with moderately to severely active systemic lupus erythematosus (SLE).

Detailed Description
-----------------
This is a Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and tolerability of escalating single subcutaneous doses of MEDI-570 in adult subjects with moderately to severely active SLE.

Official Title
-----------------
A Phase 1, Double-blind, Randomized, Single Ascending Dose Study of the Safety and Tolerability of MEDI-570 in SLE

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

Intervention / Treatment
-----------------
* Other: Placebo
* Biological: MEDI-570 0.03 MG
* Biological: MEDI-570 0.1 MG
* Biological: MEDI-570 0.3 MG
* Biological: MEDI-570 1 MG


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet or have met at least 4 of the 11 revised American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) Score greater than or equal to (>=) 6 points on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at Screening Ability to complete the study period, including follow-up period through Day 169 Willingness to forego other forms of experimental treatment during the study. Exclusion Criteria: History of cancer except basal cell carcinoma treated with apparent success with curative therapy >=1 year before randomization into the study Evidence of active or latent tuberculosis (TB) History of primary immunodeficiency Evidence of infection at any time with hepatitis B or C virus or human immunodeficiency virus (HIV)-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at Screening History of sepsis or serious, recurrent, chronic infection, current signs and symptoms of clinically significant chronic infection, or recent (within 6 months before Baseline visit) serious infection Any history or evidence of opportunistic infection within 6 months of Screening including severe cytomegalovirus (CMV) or herpetic infections (such as disseminated herpes, herpes encephalitis, ophthalmic herpes) Receipt of cyclophosphamide (intravenous or oral) within 6 months of Screening Have any absolute contraindications to skin punch biopsies, for example, a history of coagulation disorders.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>A single double-blind dose of placebo matched to MEDI-570 subcutaneous injection on Day 1. | Other: Placebo<br>* A single double-blind dose of placebo matched to MEDI-570 subcutaneous injection on Day 1.<br>|
| Experimental: MEDI-570 0.03 MG<br>A single open-label dose of MEDI-570, 0.03 milligram (mg) subcutaneous injection on Day 1. | Biological: MEDI-570 0.03 MG<br>* A single open-label dose of MEDI-570, 0.03 milligram (mg) subcutaneous injection on Day 1.<br>|
| Experimental: MEDI-570 0.1 MG<br>A single open-label dose of MEDI-570, 0.1 mg subcutaneous injection on Day 1. | Biological: MEDI-570 0.1 MG<br>* A single open-label dose of MEDI-570, 0.1 mg subcutaneous injection on Day 1.<br>|
| Experimental: MEDI-570 0.3 MG<br>A single double-blind dose of MEDI-570, 0.3 mg subcutaneous injection on Day 1. | Biological: MEDI-570 0.3 MG<br>* A single double-blind dose of MEDI-570, 0.3 mg subcutaneous injection on Day 1.<br>|
| Experimental: MEDI-570 1 MG<br>A single double-blind dose of MEDI-570, 1 mg subcutaneous injection on Day 1. | Biological: MEDI-570 1 MG<br>* A single double-blind dose of MEDI-570, 1 mg subcutaneous injection on Day 1.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 169 that were absent before treatment or that worsened relative to pretreatment state. | Day 1 to Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters for MEDI-570 | Following pharmacokinetic parameters were to be evaluated by using non-compartmental analysis: t1/2 = terminal phase elimination half-life which is the time measured for the serum concentration to decrease by one half; tmax = time to maximum observed serum concentration; Cmax = maximum observed serum concentration; AUC (0-t) = area under the serum concentration-time curve from time 0 to last measurable concentration; AUC (0-infinity) = area under the serum concentration-time curve from time 0 to extrapolated infinite time obtained from AUC (0-t) plus AUC (t-infinity); Vz/F = apparent volume of distribution, which is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug; CL/F = apparent clearance which is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Predose and postdose on Day 1; Day 3, 5, 8, 15, 29, 57, 85, 113, 141, and 169 | 
| Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit |  | Predose on Day 1; Day 85, 113, and 169 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Systemic lupus erythematosus, SLE, MEDI-570