Safety, Tolerability and Pharmacokinetics of Multiple Rising Doses of Ixazomib in Lupus Nephritis (LN)

Inclusion Criteria

• •1. In the opinion of the investigator, is capable of understanding and complying with protocol requirements.
• •2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• •3. Is female or male and aged 18 to 75 years, inclusive.
• •4. Has a diagnosis of systemic lupus erythematosus (SLE) defined by meeting either the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria or the American College of Rheumatology (ACR) criteria for the classification of SLE. The 4 criteria required by ACR classification are not required to be present at Screening for eligibility.
• •5. Has a definite diagnosis of LN based on a kidney biopsy done within 2 year of the Screening Visit which demonstrated International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV or V changes \[excluding Class III (C), IV-S (C) and IV-G (C)\] or World Health Organization (WHO) 1982 classification Class III,IV or V(excluding Class IIIc and IVd).
• •1. If no biopsy was done within 2 year of Screening Visit, biopsy can be done during the screening period as a study procedure.
• •2. Co-existence of classes is permitted.
• •6. Has a renal biopsy demonstrating either ISN/RPS or WHO class V or class V with class 2 nephritis with a UPCR of greater than (\>) 3 or the participant has a renal biopsy demonstrating either active ISN/RPS or WHO class III or IV nephritis, defined by either one of the following criteria:
• •a) A UPCR\* of \>=1.0 at Screening OR b) A UPCR\* \>0.5 at Screening and at least one of the following: i. Active urine sediment in the absence of infection or other cause within 3 months of screening, defined as at least one of the following:
• •* \>=5 red blood cells (RBC) per high power field, not due to causes other than lupus nephritis.
• •* \>=5 white blood cells (WBC) per high power field in the absence of infection.
• •* Presence of cellular casts. ii. The participant has increased levels (above upper limit of normal \[ULN\]) serum dsDNA autoantibodies at screening.
• •iii. Low complement (either C3 or C4) at Screening (\>= 25 percent \[%\] lower than lower limit of normal \[LLN\]).
• •iv. Biopsy within 3 months prior to screening visit indicating active proliferative lupus glomerulonephritis ISN/RPS class III or IV changes \[excluding Class III (C), IV-S (C) and IV-G (C)\] or WHO 1982 classification Class III or IV (excluding Class IIIc and IVd), with co-existing Class V permitted.
• •* Participants may be re-screened once for urinary sediment, proteinuria or complement levels within 2 weeks of the original screening visit.
• •* UPCR value for eligibility will be based on the average UPCR obtained from the 3 specimens collected during screening.
• •7. Has had an inadequate response, in the judgment of the Investigator, to at least 6 months of an immunosuppressive regimen including single or sequential use of at least one of the following: cyclophosphamide (CYC), mycophenolate mofetil (MMF), mycophenolic acid (MA), or azathioprine (AZA).
• •8. If the participant is on glucocorticosteroids, must be on stable dose equivalent to 20 mg/day or less of prednisone for at least 2 weeks prior to first dose of study medication. Participant who are on a stable dose equivalent to \>20 mg/day and \<=30 milligram per day (mg/day) of prednisone may be allowed to the study if reviewed by the adjudication committee and approved by the medical monitor; however, the steroid dose should be tapered.
• •9. Male participants who are sexually active with women of child bearing potential (WOCBP), even if surgically sterilized (that is, status post-vasectomy), must:
• •a) Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug.
• •10. Female participants who are of child bearing potential must:
• •a) Agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug.
• •11. This study permits the re-enrollment of a participant that has discontinued the study as a pre- treatment failure (ie, participant has not been randomized). If re-enrolled, the participant must be re-consented.