Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02141672
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02141672
Recruitment Status : Completed
First Posted : May 19, 2014
Last Update Posted : September 25, 2017
Sponsor:
Information provided by (Responsible Party):
Aurinia Pharmaceuticals Inc.

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.

Condition or disease Intervention/treatment Phase
Lupus Nephritis Drug: Voclosporin High Dose Drug: Voclosporin Low Dose Drug: Placebo Phase 2

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.

Layout table for study information
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Voclosporin Low Dose
Voclosporin, oral, 23.7 mg BID
Drug: Voclosporin Low Dose
Other Name: ISA247

Experimental: Voclosporin High Dose
Voclosporin, oral 23.7 mg BID until Week 2, then voclosporin, oral, 39.5 mg BID
Drug: Voclosporin High Dose
Other Name: ISA247

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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Complete remission as per the primary endpoint analyzed at Week 48 compared to placebo in subjects with active lupus nephritis. [ Time Frame: Week 48 ]
  2. 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).

  3. 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.

  4. Time to sustained partial remission [ Time Frame: 48 Weeks ]
    Defined as the first occurrence of partial remission which is sustained through Week 48

  5. Duration of complete remission (in months) [ Time Frame: 48 Weeks ]
  6. Complete remission at 48 weeks [ Time Frame: 48 Weeks ]
  7. Time to complete remission [ Time Frame: 48 weeks ]
  8. Partial remission [ Time Frame: Weeks 24 and 48 ]
    Defined by 50% reduction in protein/creatinine ratio from baseline at Weeks 24 and 48.

  9. Time to partial remission [ Time Frame: 48 Weeks ]
  10. 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).

  11. Time to sustained partial remission [ Time Frame: 48 Weeks ]
    Defined as the first occurrence of partial remission which is sustained through Week 48.

  12. Change from baseline in UPCR at Weeks 24 and 48. [ Time Frame: Weeks 24 and 48 ]
  13. 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 ]
  14. Change from baseline in serum creatinine, urine protein, serum albumin, eGFR at each visit measured. [ Time Frame: 50 Weeks ]
  15. 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

  16. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

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


Locations
Hide Hide 86 study locations
Layout table for location information
United States, California
AURA-LV Site
Los Angeles, California, United States, 90095
AURA-LV Site
Palo Alto, California, United States, 94305
United States, Florida
AURA-LV Site
Gainesville, Florida, United States, 32610
AURA-LV Site
Miami, Florida, United States, 33165
United States, Michigan
AURA-LV Site
Farmington Hills, Michigan, United States, 48334
United States, New York
AURA-LV Site
Brooklyn, New York, United States, 11203
AURA-LV Site
New York, New York, United States, 10016
United States, North Carolina
AURA-LV Site
Chapel Hill, North Carolina, United States, 27599
AURA-LV Site
Charlotte, North Carolina, United States, 28204
United States, Ohio
AURA-LV Site
Columbus, Ohio, United States, 43210
United States, Pennsylvania
AURA-LV Site
Hershey, Pennsylvania, United States, 17033
United States, Tennessee
AURA-LV Site
Chattanooga, Tennessee, United States, 37408
United States, Texas
AURA-LV Site
Dallas, Texas, United States, 75390
AURA-LV Site
Houston, Texas, United States, 77030
Bangladesh
AURA-LV Site
Dhaka, Bangladesh, 1207
AURA-LV Site
Dhaka, Bangladesh
Belarus
AURA-LV Site
Minsk, Belarus, 220037
AURA-LV Site
Minsk, Belarus, 220116
AURA-LV Site
Minsk, Belarus, 223040
AURA-LV Site
Vitebsk, Belarus, 210037
Bulgaria
AURA-L Site
Plovdiv, Bulgaria, 4001
AURA-LV Site
Sofia, Bulgaria, 1431
AURA-LV Site
Sofia, Bulgaria, 1527
AURA-LV Site
Varna, Bulgaria, 9010
China
AURA-LV Site
Hong Kong, China
Ecuador
AURA-LV Site
Guayaquil, Ecuador
AURA-LV Site
Quito, Ecuador
Georgia
AURA-LV Site
Tbilisi, Georgia, 0144
AURA-LV Site
Tbilisi, Georgia, 0186
Guatemala
AURA-LV Site
Guatemala City, Guatemala
Korea, Republic of
AURA-LV Site
Busan, Korea, Republic of, 602-739
AURA -LV Site
Daegu, Korea, Republic of, 705-718
AURA-LV Site
Seoul, Korea, Republic of, 110-744
AURA-LV Site
Seoul, Korea, Republic of, 158-710
AURA-LV Site
Wonju, Korea, Republic of, 220-701
Mexico
AURA-LV Site
Guadalajara, Mexico, 44280
AURA-LV Site
Mexicali, Mexico, 21100
AURA-LV Site
Oaxaca, Mexico
AURA-LV Site
Tlalpan, Mexico, 14080
AURA-LV Site
Tlalpan, Mexico
Philippines
AURA-LV Site
Angeles City, Philippines, 2009
AURA-LV Site
Batangas, Philippines, 4217
AURA-LV Site
Cebu city, Philippines, 6000
AURA-LV Site
Davao City, Philippines, 8000
AURA-LV Site
Manila, Philippines, 10000
AURA-LV Site
Manila, Philippines, 1000
AURA-LV Site
Manila, Philippines, 1003
AURA-LV Site
Quezon City, Philippines, 1102
Poland
AURA-LV Site
Katowice, Poland, 40-027
AURA-LV Site
Radom, Poland, 26-610
AURA-LV Site
Warsaw, Poland, 01-141
AURA-LV Site
Wroclaw, Poland, 50-556
Russian Federation
AURA-LV Site
Kazan, Russian Federation, 420012
AURA-LV Site
Kemerovo, Russian Federation, 650066
AURA-LV Site
Kemerovo, Russian Federation, 65009
AURA-LV Site
Moscow, Russian Federation, 111539
AURA-LV Site
Moscow, Russian Federation, 119435
AURA-LV Site
Omsk, Russian Federation, 644111
AURA-LV Site
Orenburg, Russian Federation, 460018
AURA-LV Site
Petrozavodsk, Russian Federation, 185019
AURA-LV Site
Rostov-on-Don, Russian Federation, 344022
AURA-LV Site
Saratov, Russian Federation, 410053
AURA-LV Site
St. Petersburg, Russian Federation, 191015
AURA-LV Site
St. Petersburg, Russian Federation, 197022
AURA-LV Site
St. Petersburg, Russian Federation, 197110
AURA-LV Site
Togliatti, Russian Federation, 445009
AURA-LV Site
Yaroslavl, Russian Federation, 150062
Serbia
AURA-LV Site
Belgrade, Serbia, 11000
AURA-LV Site
Nis, Serbia, 18000
Singapore
AURA-LV Site
Singapore, Singapore, 169608
AURA-LV Site
Singapore, Singapore, 529889
Spain
AURA-LV Site
Barcelona, Spain
AURA-LV
Madrid, Spain, 28034
Sri Lanka
AURA-LV Site
Colombo, Sri Lanka
AUR-LV Site
Kandy, Sri Lanka, 20000
AURA-LV Site
Nugegoda, Sri Lanka, 10100
AURA-LV Site
Ragama, Sri Lanka
Taiwan
AURA-LV Site
Kaohsiung City, Taiwan, 83301
AURA-LV Site
Taoyuan County, Taiwan, 333
Thailand
AURA-LV Site
Bangkok, Thailand, 10400
AURA-LV Site
Chiang Mai, Thailand, 50200
Ukraine
AURA-LV Site
Kharkiv, Ukraine, 61103
AURA-LV Site
Kyiv, Ukraine, 02125
AURA-LV Site
Kyiv, Ukraine, 04050
AURA-LV Site
Lutsk, Ukraine, 43005
AURA-LV Site
Zaporizhzhya, Ukraine, 69600
Sponsors and Collaborators
Aurinia Pharmaceuticals Inc.
Investigators
Layout table for investigator information
Principal Investigator: Mary Anne Dooley, MD, MPH University of North Carolina, Chapel Hill
Publications of Results:
Layout table for additonal information
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
Keywords provided by Aurinia Pharmaceuticals Inc.:
lupus nephritis
calcineurin inhibitors
voclosporin
Additional relevant MeSH terms:
Layout table for MeSH terms
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