Lupus NephritisPhase 3AURORANCT03021499
Aurinia Renal Response in Active Lupus With Voclosporin
A Phase 3 study testing Voclosporin in people with Lupus Nephritis, run by Aurinia Pharmaceuticals Inc. at 185 sites in 31 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lupus Nephritis
- What is being tested?
- Voclosporin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 358 participants
- Where
- 185 sitesin 31 countries
- Study dates
- 17 May 2017to 10 Oct 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
185 sites in 31 countries.
185 sites in 31 countries
United States59 sites
AURORA Investigative Center
Arlington, Virginia, 22205
AURORA Investigative Center
Atlanta, Georgia, 30318
AURORA Investigative Center
Aurora, Colorado, 80045
AURORA Investigative Center
Baton Rouge, Louisiana, 70809
AURORA Investigative Center
Beaumont, Texas, 77036
AURORA Investigative Center
Beverly Hills, California, 90211
AURORA Investigative Center
Boston, Massachusetts, 02118
AURORA Investigative Center
Chapel Hill, North Carolina, 27514
AURORA Investigative Center
Charleston, South Carolina, 29425
AURORA Investigative Center
Charlotte, North Carolina, 28204
AURORA Investigative Center
Charlotte, North Carolina, 28210
AURORA Investigative Center
Chattanooga, Tennessee, 37408
AURORA Investigative Center
Chicago, Illinois, 60637
AURORA Investigative Center
Clearwater, Florida, 33765
AURORA Investigative Center
Cleveland, Ohio, 44109
AURORA Investigative Center
Columbus, Georgia, 31904
AURORA Investigative Center
Columbus, Ohio, 43210
AURORA Investigative Center
Dallas, Texas, 75231
AURORA Investigative Center
Dallas, Texas, 75246
AURORA Investigative Center
Dallas, Texas, 75390
AURORA Investigative Center
DeBary, Florida, 32713
AURORA Investigative Center
Denver, Colorado, 80218
AURORA Investigative Center
Detroit, Michigan, 48201-2017
AURORA Investigative Center
El Paso, Texas, 79905
AURORA Investigative Center
El Paso, Texas, 79935
AURORA Investigative Center
Fort Lauderdale, Florida, 33309
AURORA Investigative Center
Fort Myers, Florida, 33901
AURORA Investigative Center
Grand Blanc, Michigan, 48439
AURORA Investigative Center
Great Neck, New York, 11021
AURORA Investigative Center
Greenville, North Carolina, 27834
AURORA Investigative Center
Hendersonville, Tennessee, 37075
AURORA Investigative Center
Houston, Texas, 77030
AURORA Investigative Center
Huntsville, Alabama, 35805
AURORA Investigative Center
Las Vegas, Nevada, 89128
AURORA Investigative Center
Lawrenceville, Georgia, 30046
AURORA Investigative Center
Los Angeles, California, 90022
AURORA Investigative Center
Los Angeles, California, 90024
AURORA Investigative Center
Louisville, Kentucky, 40202
AURORA Investigative Center
Miami, Florida, 33125
AURORA Investigative Center
New Bern, North Carolina, 28562
AURORA Investigative Center
New Haven, Connecticut, 06510
AURORA Investigative Center
New Orleans, Louisiana, 70121
AURORA Investigative Center
New York, New York, 10016
AURORA Investigative Center
New York, New York, 10021-4823
AURORA Investigative Center
New York, New York, 11203
AURORA Investigative Center
Newark, New Jersey, 07103
AURORA Investigative Center
Oklahoma City, Oklahoma, 73103
AURORA Investigative Center
Oklahoma City, Oklahoma, 73104
AURORA Investigative Center
Orlando, Florida, 32810
AURORA Investigative Center
Palo Alto, California, 94305
AURORA Investigative Center
Phoenix, Arizona, 85032
AURORA Investigative Center
Phoenix, Arizona, 85037
AURORA
Richmond, Virginia, 23298
AURORA Investigative Center
Rochester, Minnesota, 55905
AURORA Investigative Center
St Louis, Missouri, 63110
AURORA Investigative Center
Syracuse, New York, 13210
AURORA Investigative Center
Thousand Oaks, California, 91360
AURORA Investigative Center
Torrance, California, 90502
AURORA Investigative Center
Winter Park, Florida, 32789
Russia14 sites
AURORA Investigative Center
Kazan'
AURORA Investigative Center
Kemerovo
AURORA Investigative Center
Krasnoyarsk
AURORA Investigative Center
Moscow
AURORA Investigative Center
Omsk
AURORA Investigative Center
Petrozavodsk
AURORA Investigative Center
Rostov-on-Don
AURORA Investigative Center
Saint Petersburg, 197110
AURORA Investigative Center
Saint Petersburg
AURORA Investigative Center
Samara
AURORA Investigative Center
Saratov
AURORA Investigative Center
Tolyatti, 445009
AURORA Investigative Center
Yaroslavl, 150062
AURORA Investigative Center
Yekaterinburg
Japan12 sites
AURORA Investigative Center
Chiba
AURORA Investigative Center
Hiroshima
AURORA Investigative Center
Ishikawa
AURORA Investigative Center
Kita, Osaka
AURORA Investigative Center
Kita-ku
AURORA Investigative Center
Kitakyushu
AURORA Investigative Center
Maebashi
AURORA Investigative Center
Nagasaki
AURORA Investigative Center
Niigata
AURORA Investigative Center
Sapporo
AURORA Investigative Center
Sendai
AURORA Investigative Center
Tokyo
Mexico10 sites
AURORA Investigative Center
Baja California
AURORA Investigative Center
Coahuila
AURORA Investigative Center
Guadalajara
AURORA Investigative Center
León
AURORA Investigative Center
Mérida
AURORA Investigative Center
Mexico City
AURORA Investigative Center
Monclova
AURORA Investigative Center
Oaxaca City
AURORA Investigative Center
San Luis Potosí City
AURORA Investigative Center
Sinaloa
Turkey (Türkiye)8 sites
AURORA Investigative Center
Balcalı
AURORA Investigative Center
Bursa
AURORA Investigative Center
Efeler
AURORA Investigative Center
Fatih
AURORA Investigative Center
Istanbul
AURORA Investigative Center
Konyaalti
AURORA Investigative Center
Malatya
AURORA Investigative Center
Yenimahalle
Ukraine7 sites
AURORA Investigative Center
Kharkiv, 61103
AURORA Investigative Center
Kyiv, 02125
AURORA Investigative Center
Kyiv
AURORA Investigative Center
Lutsk
AURORA Investigative Center
Odesa, 65025
AURORA Investigative Center
Vinnytsia, 21018
AURORA Investigative Center
Zaporizhzhya
Argentina5 sites
AURORA Investigative Center
Buenos Aires
AURORA Investigative Center
Caba
AURORA Investigative Center
Córdoba
AURORA Investigative Center
La Plata
AURORA Investigative Center
San Miguel de Tucumán
Bulgaria5 sites
AURORA Investigative Center
Plovdiv
AURORA Investigative Center
Smolyan
AURORA Investigative Center
Sofia
AURORA Investigative Center
Stara Zagora, 6001
AURORA Investigative Center
Vidin
Netherlands5 sites
AURORA Investigative Center
Amsterdam
AURORA Investigative Center
Groningen
AURORA Investigative Center
Leiden
AURORA Investigative Center
Maastricht
AURORA Investigative Center
Rotterdam
Philippines5 sites
AURORA Investigative Center
Angeles City
AURORA Investigative Center
Davao City
AURORA Investigative Center
Lipa
AURORA Investigative Center
Manila
AURORA Investigative Center
Quezon City
Spain5 sites
AURORA Investigative Center
A Coruña
AURORA Investigative Center
Barcelona, 08025
AURORA Investigative Center
Madrid, 28006
AURORA Investigative Center
Madrid, 28041
AURORA Investigative Center
Valencia
Brazil4 sites
AURORA Investigative Center
Curitiba
AURORA Investigative Center
Porto Alegre
AURORA Investigative Center
Salvador
AURORA Investigative Center
São Paulo
Colombia4 sites
AURORA Investigative Center
Barranquilla
AURORA Investigative Center
Bogotá
AURORA Investigative Center
Bucaramanga
AURORA Investigative Center
Zipaquirá
South Africa4 sites
AURORA Investigative Center
Cape Town
AURORA Investigative Center
Johannesburg
AURORA Investigative Center
Pretoria
AURORA Investigative Center
Stellenbosch
South Korea4 sites
AURORA Investigative Center
Daejeon
AURORA Investigative Center
Seoul
AURORA Investigative Center
Suwon
AURORA Investigative Center
Wŏnju
Belarus3 sites
AURORA Investigative Cener
Minsk, 220116
AURORA Investigative Center
Minsk, 223040
AURORA Investigative Center
Vitebsk
Canada3 sites
AURORA Investigative Center
Edmonton, Alberta
AURORA Investigative Center
Montreal, Quebec
AURORA Investigative Center
Toronto
Chile3 sites
AURORA Investigative Center
Santiago
AURORA Investigative Center
Temuco
AURORA Investigative Center
Valdivia
Poland3 sites
AURORA Investigative Center
Katowice
AURORA Investigative Center
Warsaw
AURORA Investigative Center
Wroclaw
Taiwan3 sites
AURORA Investigative Center
Chang-hua
AURORA Investigative Center
Taichung
AURORA Investigative Center
Taoyuan
Thailand3 sites
AURORA Investigative Center
Bangkok
AURORA Investigative Center
Chiang Mai
AURORA Investigative Center
Songkhla
Costa Rica2 sites
AURORA Investigative Center
San José, 10108
AURORA Investigative Center
San José
Croatia2 sites
AURORA Investigative Center
Osijek
AURORA Investigative Center
Zagreb
Dominican Republic2 sites
AURORA Investigative Center
Santiago de los Caballeros
AURORA Investigative Center
Santo Domingo
Serbia2 sites
AURORA Investigative Center
Belgrade
AURORA Investigative Center
Niš
Vietnam2 sites
AURORA Investigative Center
Hanoi
AURORA Investigative Center
Ho Chi Minh City
About this study
Official title: A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Voclosporin (23.7 mg Twice Daily) With Placebo in Achieving Renal Response in Subjects With Active Lupus Nephritis
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.
Read the detailed description
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.
- Conditions
- Lupus Nephritis
- Being tested
- Voclosporin, Placebo Oral Capsule
- Keywords
- lupus nephritis, calcineurin inhibitors, voclosporin
- Medical subject headings
- Lupus Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VoclosporinDrug
Also called ISA247
calcineurin inhibitor
Placebo Oral CapsuleDrug
matching placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| Voclosporin | Experimental | oral, 23.7 mg twice daily (BID) Receives: Drug: Voclosporin |
| Placebo Oral Capsule | Placebo comparator | Voclosporin placebo, oral, 3 capsules twice daily (BID) Receives: Drug: Placebo Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 52 Weeks
Secondary outcomes (13)
Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 mg/mg or Less
Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 mg/mg or Less
Measured: 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.
Measured: 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.
Measured: Week 24
Number of Subjects With Partial Renal Response at Weeks 24 & 52
Number of subjects with partial Renal Response (defined as a 50% reduction in UPCR from baseline) at Week 24 and at Week 52. Baseline UPCR is the average of 2 pre-randomisation values.
Measured: Weeks 24 and 52
Number of Subjects Achieving, and Remaining in, Renal Response (Urine Protein Creatinine Ratio ≤0.5 mg/mg)
Number of subjects achieving, and remaining in, renal response (Urine Protein Creatinine ratio ≤0.5 mg/mg)
Measured: Week 52
Duration of Renal Response (Number of Days)
Duration in days until second occurrence of UPCR >0.5 mg/mg in those subjects who achieve a reduction in UPCR to below 0.5 mg/mg
Measured: Week 52
Number of Subjects Achieving 50% Reduction in Urine Protein Creatinine Ratio
Number of subjects achieving 50% reduction in Urine Protein Creatinine ratio
Measured: 52 Weeks
Time to 50% Reduction in UPCR (Number of Days)
Time in days to reduction in Urine Protein Creatinine Ratio to decrease by 50% compared to baseline. Baseline is the average of two pre-randomisation values.
Measured: 52 weeks
Change From Baseline in eGFR
Change from baseline by visit in estimated Glomerular Filtration rate. eGFR is corrected to a maximum value of 90 mL/min/1.73 m2
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Change From Baseline in UPCR
Change from baseline by visit in Urine Protein Creatinine Ratio. Baseline is the average of two pre-randomisation values.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Number of Subjects With Renal Response With Low Dose Steroids
Programmed Renal Response whilst on low dose steroids (<2.5 mg/day) for the preceding 8 Weeks at Weeks 24 and 52
Measured: Week 24 and Week 52
Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA - SLEDAI)
Change from baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score at Week 24 and 52.
The SELENA-SLEDAI tool is a cumulative and weighted index used to assess disease activity across 24 different disease descriptors in patients with lupus. A patient's SELENA-SLEDAI total score is the sum of all marked lupus related descriptors (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, leukopenia). A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.
Measured: Week 24 and Week 52
Change From Baseline in Patient Reported Outcomes
Health-related quality of life (HRQoL) information was collected using the Short Form Health Survey (SF-36) HRQoL assessment and the LupusPRO (v1.7) assessment.
The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. Scoring ranges from 0 to 100 with higher scores reflecting better health.
LupusPro assessment is a patient-reported questionnaire regarding the effect of lupus or its treatment on the patient's health, quality of life, and the medical care received related to lupus. The questionnaire consists of 43 questions within 8 HRQOL domains and 4 Non-HRQoL domains. Scores range from 0 to 100 with higher scores reflecting better quality of life.
Measured: Week 24 and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2017 (estimated)
- Study start17 May 2017
- Primary completion24 Sep 2019
- Study completion10 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Lupus NephritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 358 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aurinia Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Samir Parikh, MD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03021499
- Sponsor's protocol ID
- AUR-VCS-2016-01
- Acronym
- AURORA
- Status last verified
- Mar 2023
- First submitted
- 12 Jan 2017
- Last updated
- 27 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rovin BH, Parikh SV, Hebert LA, Chan TM, Mok CC, Ginzler EM, Hooi LS, Brunetta P, Maciuca R, Solomons N. Lupus nephritis: induction therapy in severe lupus nephritis--should MMF be considered the drug of choice? Clin J Am Soc Nephrol. 2013 Jan;8(1):147-53. doi: 10.2215/CJN.03290412. Epub 2012 Aug 9.
PubMed 22879439Ling SY, Huizinga RB, Mayo PR, Larouche R, Freitag DG, Aspeslet LJ, Foster RT. Cytochrome P450 3A and P-glycoprotein drug-drug interactions with voclosporin. Br J Clin Pharmacol. 2014 Jun;77(6):1039-50. doi: 10.1111/bcp.12309.
PubMed 24330024Ling SY, Huizinga RB, Mayo PR, Freitag DG, Aspeslet LJ, Foster RT. Pharmacokinetics of voclosporin in renal impairment and hepatic impairment. J Clin Pharmacol. 2013 Dec;53(12):1303-12. doi: 10.1002/jcph.166. Epub 2013 Oct 8.
PubMed 23996158Mayo PR, Huizinga RB, Ling SY, Freitag DG, Aspeslet LJ, Foster RT. Voclosporin food effect and single oral ascending dose pharmacokinetic and pharmacodynamic studies in healthy human subjects. J Clin Pharmacol. 2013 Aug;53(8):819-26. doi: 10.1002/jcph.114. Epub 2013 Jun 4.
PubMed 23736966Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N; ALMS Group. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011 Nov 17;365(20):1886-95. doi: 10.1056/NEJMoa1014460.
PubMed 22087680Busque S, Cantarovich M, Mulgaonkar S, Gaston R, Gaber AO, Mayo PR, Ling S, Huizinga RB, Meier-Kriesche HU; PROMISE Investigators. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transplant. 2011 Dec;11(12):2675-84. doi: 10.1111/j.1600-6143.2011.03763.x. Epub 2011 Sep 22.
PubMed 21943027Palmer BF, Tumlin JA, Radhakrishnan J, Rehaume LM, Cross JL, Huizinga RB. The kidney injury biomarker profile of patients with lupus nephritis remains unchanged with the second-generation calcineurin inhibitor voclosporin. Front Nephrol. 2025 Mar 17;5:1540471. doi: 10.3389/fneph.2025.1540471. eCollection 2025.
PubMed 40166657Menn-Josephy H, Hodge LS, Birardi V, Leher H. Efficacy of Voclosporin in Proliferative Lupus Nephritis with High Levels of Proteinuria. Clin J Am Soc Nephrol. 2024 Mar 1;19(3):309-318. doi: 10.2215/CJN.0000000000000297. Epub 2023 Dec 18.
PubMed 38110196Rovin BH, Teng YKO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, Gibson K, Kaplan J, Lisk L, Navarra S, Parikh SV, Randhawa S, Solomons N, Huizinga RB. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021 May 29;397(10289):2070-2080. doi: 10.1016/S0140-6736(21)00578-X. Epub 2021 May 7.
PubMed 33971155
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Voclosporin (23.7 mg Twice Daily) With Placebo in Achieving Renal Response in Subjects With Active Lupus Nephritis
- ClinicalTrials.gov ID
- NCT03021499
- Acronym / sponsor ID
- AURORA / AUR-VCS-2016-01
- Conditions
- Lupus Nephritis
- Keywords
- lupus nephritis, calcineurin inhibitors, voclosporin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 358 participants (actual)
- Lead sponsor
- Aurinia Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 17 May 2017 (actual)
- Primary completion
- 24 Sep 2019 (actual)
- Study completion
- 10 Oct 2019 (actual)
- First posted
- 16 Jan 2017 (estimated)
- Results
- Posted 16 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Voclosporin | Experimental | Drug: Voclosporinoral, 23.7 mg twice daily (BID) |
| Placebo Oral Capsule | Placebo comparator | Drug: Placebo Oral CapsuleVoclosporin placebo, oral, 3 capsules twice daily (BID) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- Estimated glomerular filtration rate (eGFR) of ≤45 mL/minute at screening.
- Current or medical history of:
- Other known clinically significant active medical conditions, such as:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VoclosporinAlso: ISA247calcineurin inhibitor | Drug | Voclosporin |
| Placebo Oral Capsulematching placebo capsule | Drug | Placebo Oral Capsule |
Primary outcome
Number of Participants With Adjudicated Renal Response at Week 52
Time frame: 52 Weeks
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
13 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 frame: 52 Weeks
Number of Participants With Renal Response at Week 24
Time frame: Week 24
Number of Subjects With Partial Renal Response at Weeks 24 & 52
Time frame: Weeks 24 and 52
Number of Subjects Achieving, and Remaining in, Renal Response (Urine Protein Creatinine Ratio ≤0.5 mg/mg)
Time frame: Week 52
Duration of Renal Response (Number of Days)
Time frame: Week 52
Number of Subjects Achieving 50% Reduction in Urine Protein Creatinine Ratio
Time frame: 52 Weeks
Time to 50% Reduction in UPCR (Number of Days)
Time frame: 52 weeks
Change From Baseline in eGFR
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Change From Baseline in UPCR
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Number of Subjects With Renal Response With Low Dose Steroids
Time frame: Week 24 and Week 52
Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA - SLEDAI)
Time frame: Week 24 and Week 52
Change From Baseline in Patient Reported Outcomes
Time frame: Week 24 and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22879439Rovin BH, Parikh SV, Hebert LA, Chan TM, Mok CC, Ginzler EM, Hooi LS, Brunetta P, Maciuca R, Solomons N. Lupus nephritis: induction therapy in severe lupus nephritis--should MMF be considered the drug of choice? Clin J Am Soc Nephrol. 2013 Jan;8(1):147-53. doi: 10.2215/CJN.03290412. Epub 2012 Aug 9.
- Background: PubMed 24330024Ling SY, Huizinga RB, Mayo PR, Larouche R, Freitag DG, Aspeslet LJ, Foster RT. Cytochrome P450 3A and P-glycoprotein drug-drug interactions with voclosporin. Br J Clin Pharmacol. 2014 Jun;77(6):1039-50. doi: 10.1111/bcp.12309.
- Background: PubMed 23996158Ling SY, Huizinga RB, Mayo PR, Freitag DG, Aspeslet LJ, Foster RT. Pharmacokinetics of voclosporin in renal impairment and hepatic impairment. J Clin Pharmacol. 2013 Dec;53(12):1303-12. doi: 10.1002/jcph.166. Epub 2013 Oct 8.
- Background: PubMed 23736966Mayo PR, Huizinga RB, Ling SY, Freitag DG, Aspeslet LJ, Foster RT. Voclosporin food effect and single oral ascending dose pharmacokinetic and pharmacodynamic studies in healthy human subjects. J Clin Pharmacol. 2013 Aug;53(8):819-26. doi: 10.1002/jcph.114. Epub 2013 Jun 4.
- Results publication: PubMed 22087680Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N; ALMS Group. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011 Nov 17;365(20):1886-95. doi: 10.1056/NEJMoa1014460.
- Results publication: PubMed 21943027Busque S, Cantarovich M, Mulgaonkar S, Gaston R, Gaber AO, Mayo PR, Ling S, Huizinga RB, Meier-Kriesche HU; PROMISE Investigators. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transplant. 2011 Dec;11(12):2675-84. doi: 10.1111/j.1600-6143.2011.03763.x. Epub 2011 Sep 22.
- Derived from this study: PubMed 40166657Palmer BF, Tumlin JA, Radhakrishnan J, Rehaume LM, Cross JL, Huizinga RB. The kidney injury biomarker profile of patients with lupus nephritis remains unchanged with the second-generation calcineurin inhibitor voclosporin. Front Nephrol. 2025 Mar 17;5:1540471. doi: 10.3389/fneph.2025.1540471. eCollection 2025.
- Derived from this study: PubMed 38110196Menn-Josephy H, Hodge LS, Birardi V, Leher H. Efficacy of Voclosporin in Proliferative Lupus Nephritis with High Levels of Proteinuria. Clin J Am Soc Nephrol. 2024 Mar 1;19(3):309-318. doi: 10.2215/CJN.0000000000000297. Epub 2023 Dec 18.
- Derived from this study: PubMed 33971155Rovin BH, Teng YKO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, Gibson K, Kaplan J, Lisk L, Navarra S, Parikh SV, Randhawa S, Solomons N, Huizinga RB. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021 May 29;397(10289):2070-2080. doi: 10.1016/S0140-6736(21)00578-X. Epub 2021 May 7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samir Parikh, MD principal investigator
Ohio State University
185 sites in 31 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Voclosporin in people with Lupus Nephritis, run by Aurinia Pharmaceuticals Inc. at 185 sites in 31 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 185 sites in United States, Russia, Japan, Mexico, Turkey (Türkiye) and 26 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adjudicated Renal Response at Week 52 (time frame: 52 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03021499, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2023.