Lupus (or SLE) is an autoimmune disease that can affect several systems and organs of the body. In an autoimmune disease, the function of your immune system is abnormal, in that it attacks cells and organs of your own body.  Lupus may cause fever, joint pains, skin rashes, skin sensitivity to light, and many other symptoms.  Severe lupus may involve the kidney, lungs, or nervous system.  Current treatments for lupus are mainly drugs that suppress the immune system such as a cortisone-like drug (such as prednisone) and cyclophosphamide (a potent drug sometimes used in treating certain types of cancer), and drugs commonly used to treat or prevent malaria (called antimalarials) such as hydroxychloroquine.  Many of these treatments may have serious side effects if used for a long time.

Sifalimumab, the drug being tested in this study, is a manmade monoclonal antibody that blocks the actions of type I interferons, by binding to these proteins, and therefore could help reduce symptoms of inflammation in lupus.  An antibody is a type of protein that exists naturally in the body that helps you to fight infections. 

Therefore the main goal of this study is to see whether the addition of sifalimumab to your current lupus treatment is effective in reducing the signs (such as skin lesions, arthritis) and symptoms (such as fatigue) of lupus in subjects with moderate to severe disease.  This study is also testing whether the addition of sifalimumab can improve control of your disease to the point that the dose of any cortisone-like medicines you were on at the start of the study can be reduced.

Other goals include testing the safety of sifalimumab, and testing whether your body makes antibodies against sifalimumab.

If you are a woman of child-bearing potential: 

·                   A pregnancy test will be done to confirm that you are not pregnant before you take part in this study and at each visit before you receive treatment

·                   You must avoid becoming pregnant and you and your partner must use two of the following forms of birth control during the study and follow-up period:

o    Barrier methods:  Male condom plus spermicide, Cap (plus spermicidal cream or jelly) plus male condom, Diaphragm (plus spermicidal cream or jelly) plus male condom

o    Intrauterine devices (IUDs):  Copper T, Progesterone T plus condom or spermicide

o    Hormonal contraceptives:  Implants, Hormone shot/injection, Combined pill, Minipill or patch

If you are a man with a partner of childbearing potential:

You and your partner must use two forms of birth control methods.  You must immediately contact the Study Doctor if any of the following occur:

•  Your partner becomes pregnant during the study
•  You learn that your partner became pregnant during the study
•  You learn that your partner became pregnant up to 180 after your last dose of the study drug

If you are suitable to, and you choose to take part in this study, then you will be randomly assigned to 1 of 4 study drug groups:

·         Study Drug Group 1:  Sifalimumab 200 mg (136 subjects)

·         Study Drug Group 2:  Sifalimumab 600 mg (136 subjects)

·         Study Drug Group 3:  Sifalimumab 1200 mg (136 subjects)

·         Study Drug Group 4:  Placebo (136 subjects)

Which study drug group (sifalimumab or placebo) you receive, in addition to your current treatment, is decided at random by a computer (purely by chance, like the tossing of a coin).  Neither you nor your study doctor can choose the group you will be in.  You will have a 75% chance of receiving sifalimumab (the study drug) and a 25% chance of receiving placebo (an inactive substance which looks identical to the drug being tested).   

While you are in the study, you will receive the study drug every 14 days for the first 3 doses, and then every 28 days until Day 337 (day of last dose).  The study drug will be given to you in your vein and will take between 60 and 90 minutes to administer.  This is called an intravenous or IV infusion.