A 52-Week, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a 200-mcg Dose of IPP-201101 Plus Standard of Care in Patients With Systemic Lupus Erythematosus
Condition: Lupus Erythematosus, Systemic
MeSH terms: Lupus Erythematosus, Systemic
Intervention: IPP-201101; Placebo; Standard of Care
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This current Phase 3 study will evaluate the efficacy and safety of administration of
      subcutaneous (sc) IPP-201101 in patients with active SLE.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The patient is a man or woman between 18 and 70 years of age with an established
             diagnosis of SLE as defined by ACR Classification Revised Criteria. The diagnosis is
             fulfilled provided that at least 4 criteria are met.

          -  The patient has a positive test result for ANA at screening (titer must be at least
             1:80 [by human epithelial cell tumor line (HEp-2) ANA assay]) and/or a positive test
             result for anti-dsDNA Ab at screening (value must be 30 IU/mL or more by enzyme-linked
             immunosorbent assay [ELISA]).

          -  Written informed consent is obtained.

          -  Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing
             potential, using a medically accepted method of contraception, and must agree to
             continued use of this method for the duration of the study and for 30 days after
             discontinuation of study drug treatment. Acceptable methods of contraception include
             barrier method with spermicide, abstinence (when this is in line with the preferred
             and usual lifestyle of the subject), intrauterine device (IUD), or steroidal
             contraceptive (oral, transdermal, implanted, and injected) in conjunction with a
             barrier method.

          -  The patient has a SLEDAI-2K clinical score of at least 6 points during screening. A
             SLEDAI-2K clinical score is the calculated score without inclusion of the points that
             may be contributed by having a positive titer for anti-dsDNA Ab or decreased serum
             complement levels.

          -  The patient does not have an "A" score on the BILAG-2004 scale. If the patient is
             using oral corticosteroids, the weekly cumulative dose must not exceed 80 mg of
             prednisone equivalent; the weekly dose must be stable over the 4 weeks preceding the
             1st dose of study drug.

          -  If the patient is using antimalarials, methotrexate, leflunomide, mycophenolate
             mofetil (MMF), or azathioprine, the start date must be at least 3 months prior to the
             1st dose of study drug, and the daily dose must be stable over the 4 weeks preceding
             the 1st dose of study drug.

          -  If the patient is not currently using corticosteroids, antimalarials, methotrexate,
             MMF, or azathioprine, the last dose (in case of previous use) must be at least 4 weeks
             prior to the 1st dose of study drug. For leflunomide, the stop date must be at least 8
             weeks before the 1st dose of study drug unless an adequate cholestryamine washout has
             been performed. If cholestyramine washout is performed, the last use of leflunomide
             must be at least 4 weeks before the 1st dose of study drug.

          -  The patient must be willing and able to comply with study restrictions, to remain at
             the study center for the required duration during each study visit, and to return to
             the study center for the final assessment as specified in this protocol.

        Exclusion Criteria:

          -  The patient has been treated with intramuscular or intravenous (iv) pulse steroids
             (ie, 250 to 1000 mg iv total daily dose of methylprednisolone) within 4 weeks of the
             1st dose of study drug. The use of intra-articular steroids may be allowed after
             consultation with the medical expert.

          -  The patient has received tacrolimus, cyclosporin A, or iv immunoglobulins (IVIG)
             within 3 months of the 1st dose of study drug.

          -  The patient has received cyclophosphamide within 6 months prior to the 1st dose of
             study drug.

          -  The patient has been treated for SLE with agents such as fusion proteins, therapeutic
             proteins, or monoclonal antibodies or antibody fragments, within 6 months of the 1st
             dose of study drug.

          -  The patient has received B-cell depleting agents such as rituximab, belimumab or
             epratuzumab within one year of the 1st dose and has not yet normalized the B-cell
             count (ie, CD20+ B-cell count is less than normal range and the absolute lymphocyte
             count [ALC] is less than normal range).

          -  The patient has New York Heart Association (NYHA) Class III or IV congestive heart
             failure.

          -  The patient has an estimated glomerular filtration rate (eGFR) of less than 30
             mL/min/1.73 m2 (via Modification of Diet in Renal Disease [MDRD] equation).

          -  The patient has an aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
             value greater than 2 times the upper limit of the normal range (ULN) or a total
             bilirubin level greater than 1.5 times ULN.

          -  The patient has a planned immunization with a live or live attenuated vaccine within 3
             months prior to administration of the 1st dose of study drug and for 3 months after
             administration of the last dose of study drug.

          -  The patient has any clinically significant abnormalities on ECG that are not related
             to SLE, as determined by the investigator. Patients with stable ECG changes without
             evidence of active cardiovascular disease may participate at the discretion of the
             investigator and medical monitor.

          -  The patient has an ongoing active systemic infection requiring treatment or a history
             of severe infection, such as hepatitis or pneumonia, in the 3 months prior to
             administration of the 1st dose of study drug. Less severe infections in the 3 months
             prior to administration of the 1st dose of study drug are permitted at the discretion
             of the investigator and medical monitor.

          -  The patient has any concomitant medical condition unrelated to SLE that may interfere
             with his or her safety or with evaluation of the study drug, as determined by the
             investigator.

          -  The patient has a history of a medical condition other than SLE that has required
             treatment with oral corticosteroids in excess of 80 mg of prednisone equivalent/week
             within 3 months of the 1st dose of study drug.

          -  The patient has a positive test result for hepatitis B surface antigen (HBsAg) or
             hepatitis C virus antibody (HCV Ab).

          -  The patient has a known positive history of antibodies to human immunodeficiency virus
             (HIV) or HIV disease or other immunosuppressive state (eg, agammaglobulinemia, etc).

          -  The patient has a history of alcohol or substance dependence or abuse (with the
             exception of nicotine),according to the Diagnostic and Statistical Manual of Mental
             Disorders of the American Psychiatric Association, Fourth Edition, Text Revision
             (DSM-IV-TR), within 3 months of the screening visit or has current substance abuse.

          -  The patient has a history of severe allergic reactions to or hypersensitivity to any
             component of the study drug or placebo.

          -  The patient has undergone or is undergoing treatment with another investigational drug
             for the treatment of lupus within 6 months prior to the 1st dose of study drug or has
             received any other investigational drug for any other condition within 4 weeks prior
             to the 1st dose of study drug.

          -  The patient has previously participated in a ImmuPharma- or ImmuPharma-sponsored
             clinical study with IPP-201101.

          -  The patient is a pregnant or lactating woman. (Any women becoming pregnant during the
             study will be withdrawn from the study.)

          -  The patient is unlikely to comply with the study protocol or is unsuitable for any
             other reason, as judged by the investigator or medical monitor.