AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (AURA-LV)
Condition: Lupus Nephritis
MeSH terms: Nephritis; Lupus Nephritis
Intervention: Voclosporin High Dose; Voclosporin Low Dose; Placebo
Intervention MeSH terms: Cyclosporine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 265.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: lupus nephritis; calcineurin inhibitors; voclosporin

Summary:

      To assess the efficacy of 2 doses of voclosporin compared to placebo in achieving complete
      remission after 24 weeks of therapy in subjects with active lupus nephritis.
    

Eligibility criteria:

        Inclusion Criteria:

        Male or female subjects aged 18 to 75 years.

        Diagnosis of systemic lupus erythematosus (SLE) according to the American College of
        Rheumatology criteria.

        Kidney biopsy within 6 months prior to Screening (Visit 1) with a histologic diagnosis of
        lupus nephritis (International Society of Nephrology/Renal Pathology Society 2003
        classification of lupus nephritis) Classes III, IV-S or IV-G, (A) or (A/C); or Class V,
        alone or in combination with Class III or IV.

        Laboratory evidence of active nephritis at screening, defined as:

          -  Class III, IV-S or IV-G: Confirmed proteinuria ≥1,500 mg/24 hours when assessed by 24
             hour urine collection, defined by a UPCR of ≥1.5 mg/mg assessed in a first morning
             void urine specimen (2 samples).

          -  Class V (alone or in combination with Class III or IV): Confirmed proteinuria ≥2,000
             mg/24 hours when assessed by 24 hour urine collection, defined by a UPCR of ≥2 mg/mg
             assessed in a first morning void urine specimen (2 samples).

        Exclusion Criteria:

        Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease
        Epidemiology Collaboration equation of ≤45 mL/min/1.73 m2.

        Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to
        require dialysis during the study period.

        A previous kidney transplant or planned transplant within study treatment period.

        In the opinion of the Investigator, subject does not require long-term immunosuppressive
        treatment (in addition to corticosteroids).

        Current or medical history of:

          -  Pancreatitis or gastrointestinal hemorrhage within 6 months prior to screening.

          -  Active unhealed peptic ulcer within 3 months prior to screening. If an ulcer has
             healed and the subject is on adequate therapy, the subject may be randomized.

          -  Congenital or acquired immunodeficiency.

          -  Clinically significant drug or alcohol abuse 2 years prior to screening.

          -  Malignancy within 5 years of screening, with the exception of basal and squamous cell
             carcinomas treated by complete excision. Subjects with cervical dysplasia that is
             cervical intraepithelial neoplasia 1, but have been treated with conization or loop
             electrosurgical excision procedure, and have had a normal repeat PAP are allowed.

          -  Lymphoproliferative disease or previous total lymphoid irradiation.

          -  Severe viral infection (such as CMV, HBV, HCV) within 3 months of screening; or known
             human immunodeficiency virus infection.

          -  Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking
             prophylaxis with isoniazid.

        Other known clinically significant active medical conditions, such as:

          -  Severe cardiovascular disease including congestive heart failure, history of cardiac
             dysrhythmia or congenital long QT syndrome.

          -  Liver dysfunction (aspartate aminotransferase, alanine aminotransferase, or bilirubin
             greater than 2.5 times the upper limit of normal) at screening and confirmed before
             randomization.

          -  Chronic obstructive pulmonary disease or asthma requiring oral steroids.

          -  Bone marrow insufficiency unrelated to active SLE (according to Investigator judgment)
             with white blood cell count <2,500/mm3; absolute neutrophil count <1.3 x 103/μL;
             thrombocytopenia (platelet count <50,000/mm3).

          -  Active bleeding disorders.

          -  Current infection requiring IV antibiotics.

        Any overlapping autoimmune condition for which the condition or the treatment of the
        condition may affect the study assessments or outcomes. Overlapping conditions for which
        the condition or treatment is not expected to affect assessments or outcomes are not
        excluded.

        Subjects who are pregnant, breast feeding or, if of childbearing potential, not using
        adequate contraceptive precautions.