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AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (AURA-LV) (AURA-LV)

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ClinicalTrials.gov Identifier: NCT02141672
Recruitment Status : Completed
First Posted : May 19, 2014
Results First Posted : May 18, 2021
Last Update Posted : May 18, 2021
Sponsor:
Information provided by (Responsible Party):
Aurinia Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE May 14, 2014
First Posted Date  ICMJE May 19, 2014
Results First Submitted Date  ICMJE February 19, 2021
Results First Posted Date  ICMJE May 18, 2021
Last Update Posted Date May 18, 2021
Study Start Date  ICMJE June 2014
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2021)
Number of Subjects Achieving Complete Renal Remission at 24 Weeks [ Time Frame: week 24 ]
Complete remission is defined as:
  • Confirmed protein/creatinine ratio of ≤0.5 mg/mg and
  • eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.
Original Primary Outcome Measures  ICMJE
 (submitted: May 15, 2014)
The number of subjects achieving complete remission at 24 Weeks [ Time Frame: 24 weeks ]
Complete remission is defined as:
  • Confirmed protein/creatinine ratio of ≤0.5 mg/mg and
  • No confirmed decrease from baseline in eGFR of ≥20%. Subjects who receive rescue medication for lupus or ≥10 mg prednisone after Week 16 will not be considered as achieving complete remission.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2021)
  • Number of Subjects Achieving Complete Renal Remission at 48 Weeks [ Time Frame: Week 48 ]
    Complete remission is defined as:
    • Confirmed protein/creatinine ratio of ≤0.5 mg/mg and
    • eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.
  • Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids [ Time Frame: Weeks 24 and 48 ]
    Complete remission is defined as:
    • Confirmed protein/creatinine ratio of ≤0.5 mg/mg and
    • eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.
    Low-dose steroids is defined as use of ≤5 mg prednisone for 8 weeks leading up to the Week 24 visit date or for 12 weeks leading up to the Week 48 visit date.
  • Time to Complete Remission (Number of Weeks) [ Time Frame: week 48 ]
    Time to Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR ≤ 0.5mg in the absence of rescue medication.
  • Time to Sustained Early Complete Remission (Number of Weeks) [ Time Frame: week 48 ]
    Time to Sustained Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR ≤ 0.5mg occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication.
  • Number of Subjects Achieving Sustained Early Complete Remission [ Time Frame: week 48 ]
    Sustained early complete remission defined as complete remission that occurred on or before Week 24 and was sustained through Week 48
  • Time to Partial Remission (Number of Weeks) [ Time Frame: week 48 ]
    Time to partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication.
  • Number of Subjects Achieving Partial Remission [ Time Frame: week 48 ]
    Partial remission is defined as a 50% reduction in UPCR from baseline at Week 24 and Week 48.
  • Number of Subjects Achieving, and Remaining in, Complete Remission [ Time Frame: week 48 ]
    Sustained complete remission defined as the first occurrence of complete remission that was sustained through Week 48
  • Duration of Complete Remission (Number of Weeks) [ Time Frame: week 48 ]
    Duration of Complete Remission is defined as time of first occurrence of UPCR ≤ 0.5 mg/mg until the second increase above 0.5 mg/mg (i.e. a single occurrence above 0.5 is permitted) or use of rescue medication.
  • Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks [ Time Frame: week 24 and 48 ]
    Number of patients with partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction at week 24 or week 48 in the absence of rescue medication.
  • Time to Sustained Partial Remission (Number of Weeks) [ Time Frame: week 48 ]
    Time to sustained partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication.
  • Number of Subjects Achieving Sustained Partial Remission [ Time Frame: week 48 ]
    Sustained partial remission defined as the first occurrence of partial remission that was sustained through Week 48
  • Time to Sustained Early Partial Remission (Number of Weeks) [ Time Frame: week 48 ]
    Time to sustained early partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication.
  • Number of Subjects Achieving Sustained Early Partial Remission [ Time Frame: week 48 ]
    Early partial remission defined as partial remission that occurred on or before Week 24 and was sustained through Week 48
  • Change From Baseline in UPCR at Weeks 24 and 48 [ Time Frame: Baseline, Week 24 and Week 48 ]
    Change from baseline in urine protein creatinine ratio at weeks 24 and 48
  • Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score [ Time Frame: Baseline, Week 24 and Week 48 ]
    The SELENA-SLEDAI assesses disease activity within the last 10 days. Twenty-four items are scored for nine organ systems, and summed to a maximum of 105 points. A score of 6 is considered clinically significant and indicates active disease. For analysis purposes, a score ≥6 was categorized as "high". The 24 items are as follows: seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, new rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, increased DNA binding, fever, thrombocytopenia, and leukopenia.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2014)
  • Complete remission as per the primary endpoint analyzed at Week 48 compared to placebo in subjects with active lupus nephritis. [ Time Frame: Week 48 ]
  • Complete remission in the presence of low dose steroids at Week 24 and Week 48. [ Time Frame: Weeks 24 and 48 ]
    Complete remission in the presence of low dose steroids at Week 24 (defined as confirmed complete remission and ≤5 mg prednisone for ≥8 weeks) and Week 48 (defined as confirmed complete remission and ≤5 mg prednisone for ≥12 weeks).
  • Time to (and proportion achieving) early, sustained complete remission [ Time Frame: 24 Weeks ]
    defined as complete remission which occurs on or before Week 24 which is sustained through Week 48.
  • Time to sustained partial remission [ Time Frame: 48 Weeks ]
    Defined as the first occurrence of partial remission which is sustained through Week 48
  • Duration of complete remission (in months) [ Time Frame: 48 Weeks ]
  • Complete remission at 48 weeks [ Time Frame: 48 Weeks ]
  • Time to complete remission [ Time Frame: 48 weeks ]
  • Partial remission [ Time Frame: week 24 and 48 ]
    Defined by 50% reduction in protein/creatinine ratio from baseline at Weeks 24 and 48.
  • Time to partial remission [ Time Frame: 48 Weeks ]
  • Time to (and proportion achieving) early, sustained partial remission [ Time Frame: 48 Weeks ]
    Partial remission which occurs on or before Week 24 which is sustained through Week 48).
  • Time to sustained partial remission [ Time Frame: 48 Weeks ]
    Defined as the first occurrence of partial remission which is sustained through Week 48.
  • Change From Baseline in UPCR at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Change from baseline in the Safety of Exogenous Estrogens in Lupus Erythematosus National Assessment (SELENA) - SLEDAI score at Weeks 24 and 48. [ Time Frame: Weeks 24 and 48 ]
  • Change from baseline in serum creatinine, urine protein, serum albumin, eGFR at each visit measured. [ Time Frame: 50 Weeks ]
  • Proportion of subjects with active urinary sediment at each visit measured. [ Time Frame: 50 Weeks ]
    Defined by >10 red blood cells per high powered field (RBC/hpf) with dysmorphic red blood cells (RBC) and/or RBC casts on urinalysis of a urine sample which has a minimum volume of 50 mL
  • Change from baseline in immunology parameters (C3, C4, and anti-double-stranded deoxyribonucleic acid (dsDNA) and biomarkers at each visit measured. [ Time Frame: 50 Weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (AURA-LV)
Official Title  ICMJE A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Voclosporin (23.7 mg BID, or 39.5 mg BID) With Placebo in Achieving Remission in Patients With Active Lupus Nephritis
Brief 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.
Detailed Description Voclosporin is a next generation CNI intended for use in the prevention of organ graft rejection and for the treatment of autoimmune diseases. The aim of the current study is to investigate whether voclosporin added to the standard of care treatment in active LN is able to reduce disease activity, as measured by a reduction in proteinuria. Two doses of voclosporin will be studied and compared in a placebo controlled trial on a background of MMF and corticosteroids. Patients 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 (American College of Rheumatology) 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 while demonstrating an acceptable safety profile.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Lupus Nephritis
Intervention  ICMJE
  • Drug: Voclosporin High Dose
    Other Name: ISA247
  • Drug: Voclosporin Low Dose
    Other Name: ISA247
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Voclosporin Low Dose
    Voclosporin, oral, 23.7 mg BID
    Intervention: Drug: Voclosporin Low Dose
  • Experimental: Voclosporin High Dose
    Voclosporin, oral 23.7 mg BID until Week 2, then voclosporin, oral, 39.5 mg BID
    Intervention: Drug: Voclosporin High Dose
  • Placebo Comparator: Placebo

    Low dose: Voclosporin placebo, oral, 3 capsules BID

    High dose: Voclosporin placebo, oral, 3 capsules BID until Week 2 then voclosporin placebo, oral, 5 capsules BID

    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 21, 2017)
265
Original Estimated Enrollment  ICMJE
 (submitted: May 15, 2014)
222
Actual Study Completion Date  ICMJE January 2017
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bangladesh,   Belarus,   Bulgaria,   China,   Ecuador,   Georgia,   Guatemala,   Korea, Republic of,   Mexico,   Philippines,   Poland,   Russian Federation,   Serbia,   Singapore,   Spain,   Sri Lanka,   Taiwan,   Thailand,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02141672
Other Study ID Numbers  ICMJE AUR-VCS-2012-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aurinia Pharmaceuticals Inc.
Study Sponsor  ICMJE Aurinia Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mary Anne Dooley, MD, MPH University of North Carolina, Chapel Hill
PRS Account Aurinia Pharmaceuticals Inc.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP