Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Proliferative Lupus Nephritis
Condition: Lupus Nephritis
MeSH terms: Nephritis; Lupus Nephritis
Intervention: Anifrolumab; Placebo
Intervention description: Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112; Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 147.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: lupus, nephritis, randomized, placebo, anifrolumab, safety, efficacy, adult

Summary:

      The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment
      regimen of two doses of anifrolumab versus placebo in adult subjects with active
      proliferative lupus nephritis (LN).
    

Eligibility criteria:

        Main Inclusion Criteria:

          1. Age 18 through 70 years at the time of screening

          2. Fulfils at least 4 of the 11 criteria of the revised 1982 ACR classification criteria
             for SLE, at least one of which must be:

               1. Positive antinuclear antibody (ANA) test (1:40 or higher) or

               2. Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive
                  results), as per the centrallaboratory; or

               3. Anti-Smith antibody at screening elevated to above normal (ie, positive or
                  equivocal results) as per the central laboratory

          3. Class III (±Class V) or Class IV (±Class V) LN according to the World Health
             Organisation (WHO) or 2003 ISN/RPS classification based on a renal biopsy obtained
             within 12 weeks prior to signing the ICF or during the screening period:

          4. Urine protein to creatinine ratio >1 gm/gm (113.17 mg/mmol), obtained on a 24-hour
             urine collection at screening

          5. Estimated glomerular filtration rate ≥35 mL/min/1.73 m2

          6. Must not have active or latent TB on either chest radiograph or by Quantiferon gold
             test

          7. Women of childbearing potential must have a negative serum beta-hCG test at screening
             and negative urine pregnancy test prior to the first dose of sponsor-provided MMF.

        Main Exclusion Criteria:

          1. Receipt of any investigational product (small molecule or biologic) or commercially
             available biologic agent within four weeks or 5 half lives prior to signing of the
             ICF, whichever is greater

          2. Pure Class V membranous LN on a renal biopsy obtained within 12 weeks prior to signing
             ICF or during the screening period

          3. Known intolerance to ≤1.0 gm/day of MMF

          4. History of dialysis within 12 months prior to signing the ICF or expected need for
             renal replacement therapy (dialysis or renal transplant) within a 6 month period after
             enrolment

          5. Subjects, who at the time of signing the ICF, received any of the following
             immunosuppressive therapies after their qualifying biopsy

               1. Oral corticosteroids >0.5 mg/kg/day for more than 8 weeks or

               2. Oral or IV pulse methylprednisolone >3.0 gm (cumulative dose) or

               3. IV cyclophosphamide >2 pulses of high-dose (≥0.5 gm/m2) or >4 doses of low dose
                  (500 mg every 2 weeks) or

               4. Average MMF >2.5 gm/day (>1800 mg/day of enteric-coated mycophenolate sodium) for
                  more than 8 weeks or

               5. Tacrolimus >4 mg/day for more than 8 weeks

          6. Major surgery within 8 weeks before signing the ICF or major surgery planned during
             the study period

          7. History of any non-SLE disease that has required treatment with oral or parenteral
             corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to
             signing the ICF

          8. Confirmed positive test for hepatitis B or hepatitis C

          9. Any severe herpes infection at any time prior to randomization

         10. Opportunistic infection requiring hospitalisation or parenteral antimicrobial
             treatment within 3 years prior to randomization (vaginal, oral and skin candidiasis is
             not an exclusionreason).

         11. History of cancer, apart from:

               1. Squamous or basal cell carcinoma of the skin that has been successfully treated

               2. Cervical cancer in situ that has been successfully treated

         12. Concurrent enrolment in another clinical study with an IP within 4 weeks prior to ICF
             signing or within 5 half-lives of the IP used in that clinical study, whichever is
             longer.

         13. During screening (within 30 days before Day 1 [Week 0 visit]), any of the following:

               1. Aspartate transaminase (AST) >2.5×upper limit of normal (ULN)

               2. Alanine transaminase (ALT) >2.5×ULN

               3. Total bilirubin >ULN (unless due to Gilbert's syndrome [based on Investigator's
                  judgement])

               4. Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjects
                  only)

               5. Neutrophil count <1x103/μL (or <1.0 GI/L)

               6. Platelet count <25x103/μL (or <25 GI/L)

               7. Haemoglobin <8 g/dL (or <80 g/L).