AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (AURA-LV) (AURA-LV)
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| ClinicalTrials.gov Identifier: NCT02141672 |
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Recruitment Status :
Completed
First Posted : May 19, 2014
Last Update Posted : September 25, 2017
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lupus Nephritis | Drug: Voclosporin High Dose Drug: Voclosporin Low Dose Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 265 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Study Start Date : | June 2014 |
| Actual Primary Completion Date : | July 2016 |
| Actual Study Completion Date : | January 2017 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Voclosporin Low Dose
Voclosporin, oral, 23.7 mg BID
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Drug: Voclosporin Low Dose
Other Name: ISA247 |
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Experimental: Voclosporin High Dose
Voclosporin, oral 23.7 mg BID until Week 2, then voclosporin, oral, 39.5 mg BID
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Drug: Voclosporin High Dose
Other Name: ISA247 |
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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 |
Drug: Placebo |
- 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
- eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who receive rescue medication for lupus or ≥10 mg prednisone for >3 consecutive days or >7 days total from Weeks 16-26 will not be considered as achieving complete remission.
- 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: Weeks 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 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 ]
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02141672
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| Principal Investigator: | Mary Anne Dooley, MD, MPH | University of North Carolina, Chapel Hill |
| Responsible Party: | Aurinia Pharmaceuticals Inc. |
| ClinicalTrials.gov Identifier: | NCT02141672 |
| Other Study ID Numbers: |
AUR-VCS-2012-01 |
| First Posted: | May 19, 2014 Key Record Dates |
| Last Update Posted: | September 25, 2017 |
| Last Verified: | March 2017 |
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lupus nephritis calcineurin inhibitors voclosporin |
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Nephritis Lupus Nephritis Kidney Diseases Urologic Diseases Glomerulonephritis Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Cyclosporine |
Antifungal Agents Anti-Infective Agents Dermatologic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Calcineurin Inhibitors |