Aurinia Renal Response in Active Lupus With Voclosporin

Aurinia Pharmaceuticals Inc.358 enrolled

Overview

The purpose of this study is to assess the efficacy of voclosporin compared with placebo in achieving renal response after 52 weeks of therapy in subjects with active lupus nephritis.

The aim of the current study is to investigate whether voclosporin, added to the standard of care treatment in active lupus nephritis (LN), is able to reduce disease activity over a treatment period of 52 weeks. The background therapy will be mycophenolate mofetil (MMF) and initial treatment with IV methylprednisolone, followed by a reducing course of oral corticosteroids. Subjects with active, flaring LN will be eligible to enter the study. They are required to have a diagnosis of LN according to established diagnostic criteria and clinical and biopsy features suggestive of active nephritis. Efficacy will be assessed by the ability of the drug combination to reduce the level of proteinuria (as measured by Urine Protein Creatinine Ratio (UPCR)) while demonstrating an acceptable safety profile.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

358

Conditions

Lupus Nephritis

Interventions

VoclosporinDRUG

calcineurin inhibitor

Placebo Oral CapsuleDRUG

matching placebo capsule

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: \- Subjects with evidence of active nephritis, defined as follows: * Kidney biopsy result within 2 years prior to screening indicating Class III, IV-S, IV-G (alone or in combination with Class V), or Class V LN with a doubling or greater increase of UPCR within the last 6 months to a minimum of ≥1.5 mg/mg for Class III/IV or to a minimum of ≥2 mg/mg for Class V at screening. Biopsy results over 6 months prior to screening must be reviewed with a medical monitor to confirm eligibility. OR * Kidney biopsy result within 6 months prior to screening indicating Class III, IV-S or IV-G (alone or in combination with Class V) LN with a UPCR of ≥1.5 mg/mg at screening. OR * Kidney biopsy result within 6 months prior to screening indicating Class V LN and a UPCR of ≥2 mg/mg at screening. * Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline. Exclusion Criteria: * Estimated glomerular filtration rate (eGFR) of ≤45 mL/minute at screening. * Current or medical history of: * Congenital or acquired immunodeficiency. * In the opinion of the Investigator, clinically significant drug or alcohol abuse within 2 years prior to screening. * Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. * Lymphoproliferative disease or previous total lymphoid irradiation. * Severe viral infection or known HIV 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, liver dysfunction or chronic obstructive pulmonary disease or asthma requiring oral steroids or any other overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes.

Locations (185)

Outcomes

Primary Outcomes

Number of Participants With Adjudicated Renal Response at Week 52

The primary efficacy endpoint was the number of subjects showing renal response at Week 52. Renal response was adjudicated based on blinded data by an independent Clinical Endpoints Committee based on meeting the following criteria * UPCR of ≤0.5 mg/mg \& * eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of \>20% \& * Received no rescue medication for LN \& * Did not receive more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during Weeks 44 through 52, prior to assessment Note:To be disqualified from renal response, the subject had to fail both eGFR measures (i.e., confirmed eGFR \<60 mL/min/1.73 m2 \& confirmed \>20% drop from baseline) \& have an associated treatment-related or disease-related AE that impacted eGFR Withdrawals prior to Week 52 with insufficient Week 52 data to determine response were defined non responders. Subjects who discontinued study drug but continued to attend study visits had their data assessed for response

Time frame: 52 Weeks

Secondary Outcomes

Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 mg/mg or Less

Time frame: 52 Weeks

Time to Urine Protein Creatinine Ratio of ≤0.5 mg/mg (Number of Days)

Time in days to reduction in Urine Protein Creatinine Ratio to decrease to 0.5 mg/mg or less.

Time frame: 52 Weeks

Number of Participants With Renal Response at Week 24

Number of subjects showing renal response at Week 24. Renal response was adjudicated based on blinded data by an Independent Clinical Endpoints Committee based on the following criteria: UPCR of ≤0.5 mg/mg, \& eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of \>20%, and Received no rescue medication for LN \& Did not receive more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during Weeks 16 through 24, just prior to the renal response assessment. Note:To be disqualified from renal response, the subject had to fail both eGFR measures (i.e., confirmed eGFR \<60 mL/min/1.73 m2 AND confirmed \>20% drop from BL) \& have an associated treatment-related or disease-related AE that impacted eGFR. Subjects who withdrew prior to the Week 24 assessment and provided insufficient Week 24 data to determine response were defined as non-responders. Subjects who discontinued study drug but continued to attend study visits had their data assessed for response.

Data from ClinicalTrials.gov

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