Clinical trial NCT03021499: Aurinia Renal Response in Active Lupus With Voclosporin
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lupus Nephritis
Keywords: lupus nephritis
calcineurin inhibitors
voclosporin
Lead sponsor: Aurinia Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2017-01-16
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adjudicated Renal Response at Week 52
timeFrame: 52 Weeks
Secondary outcomes:
measure: Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 mg/mg or Less
timeFrame: 52 Weeks
measure: Time to Urine Protein Creatinine Ratio of ≤0.5 mg/mg (Number of Days)
timeFrame: 52 Weeks
measure: Number of Participants With Renal Response at Week 24
timeFrame: Week 24
measure: Number of Subjects With Partial Renal Response at Weeks 24 & 52
timeFrame: Weeks 24 and 52
measure: Number of Subjects Achieving, and Remaining in, Renal Response (Urine Protein Creatinine Ratio ≤0.5 mg/mg)
timeFrame: Week 52
measure: Duration of Renal Response (Number of Days)
timeFrame: Week 52
measure: Number of Subjects Achieving 50% Reduction in Urine Protein Creatinine Ratio
timeFrame: 52 Weeks
measure: Time to 50% Reduction in UPCR (Number of Days)
timeFrame: 52 weeks
measure: Change From Baseline in eGFR
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
measure: Change From Baseline in UPCR
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
measure: Number of Subjects With Renal Response With Low Dose Steroids
timeFrame: Week 24 and Week 52
measure: Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA - SLEDAI)
timeFrame: Week 24 and Week 52
measure: Change From Baseline in Patient Reported Outcomes
timeFrame: Week 24 and Week 52
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: AURORA Investigative Center
state: Alabama
city: Phoenix
country: United States
facility: AURORA Investigative Center
state: Arizona
city: Phoenix
country: United States
facility: AURORA Investigative Center
state: Arizona
city: Beverly Hills
country: United States
facility: AURORA Investigative Center
state: California
city: Los Angeles
country: United States
facility: AURORA Investigative Center
state: California
city: Los Angeles
country: United States
facility: AURORA Investigative Center
state: California
city: Palo Alto
country: United States
facility: AURORA Investigative Center
state: California
city: Thousand Oaks
country: United States
facility: AURORA Investigative Center
state: California
city: Torrance
country: United States
facility: AURORA Investigative Center
state: California
city: Aurora
country: United States
facility: AURORA Investigative Center
state: Colorado
city: Denver
country: United States
facility: AURORA Investigative Center
state: Colorado
city: New Haven
country: United States
facility: AURORA Investigative Center
state: Connecticut
city: Clearwater
country: United States
facility: AURORA Investigative Center
state: Florida
city: DeBary
country: United States
facility: AURORA Investigative Center
state: Florida
city: Fort Lauderdale
country: United States
facility: AURORA Investigative Center
state: Florida
city: Fort Myers
country: United States
facility: AURORA Investigative Center
state: Florida
city: Miami
country: United States
facility: AURORA Investigative Center
state: Florida
city: Orlando
country: United States
facility: AURORA Investigative Center
state: Florida
city: Winter Park
country: United States
facility: AURORA Investigative Center
state: Florida
city: Atlanta
country: United States
facility: AURORA Investigative Center
state: Georgia
city: Columbus
country: United States
facility: AURORA Investigative Center
state: Georgia
city: Lawrenceville
country: United States
facility: AURORA Investigative Center
state: Georgia
city: Chicago
country: United States
facility: AURORA Investigative Center
state: Illinois
city: Louisville
country: United States
facility: AURORA Investigative Center
state: Kentucky
city: Baton Rouge
country: United States
facility: AURORA Investigative Center
state: Louisiana
city: New Orleans
country: United States
facility: AURORA Investigative Center
state: Louisiana
city: Boston
country: United States
facility: AURORA Investigative Center
state: Massachusetts
city: Detroit
country: United States
facility: AURORA Investigative Center
state: Michigan
city: Grand Blanc
country: United States
facility: AURORA Investigative Center
state: Michigan
city: Rochester
country: United States
facility: AURORA Investigative Center
state: Minnesota
city: Saint Louis
country: United States
facility: AURORA Investigative Center
state: Missouri
city: Las Vegas
country: United States
facility: AURORA Investigative Center
state: Nevada
city: Newark
country: United States
facility: AURORA Investigative Center
state: New Jersey
city: Great Neck
country: United States
facility: AURORA Investigative Center
state: New York
city: New York
country: United States
facility: AURORA Investigative Center
state: New York
city: New York
country: United States
facility: AURORA Investigative Center
state: New York
city: New York
country: United States
facility: AURORA Investigative Center
state: New York
city: Syracuse
country: United States
facility: AURORA Investigative Center
state: New York
city: Chapel Hill
country: United States
facility: AURORA Investigative Center
state: North Carolina
city: Charlotte
country: United States
facility: AURORA Investigative Center
state: North Carolina
city: Charlotte
country: United States
facility: AURORA Investigative Center
state: North Carolina
city: Greenville
country: United States
facility: AURORA Investigative Center
state: North Carolina
city: New Bern
country: United States
facility: AURORA Investigative Center
state: North Carolina
city: Cleveland
country: United States
facility: AURORA Investigative Center
state: Ohio
city: Columbus
country: United States
facility: AURORA Investigative Center
state: Ohio
city: Oklahoma City
country: United States
facility: AURORA Investigative Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: AURORA Investigative Center
state: Oklahoma
city: Charleston
country: United States
facility: AURORA Investigative Center
state: South Carolina
city: Chattanooga
country: United States
facility: AURORA Investigative Center
state: Tennessee
city: Hendersonville
country: United States
facility: AURORA Investigative Center
state: Tennessee
city: Beaumont
country: United States
facility: AURORA Investigative Center
state: Texas
city: Dallas
country: United States
facility: AURORA Investigative Center
state: Texas
city: Dallas
country: United States
facility: AURORA Investigative Center
state: Texas
city: Dallas
country: United States
facility: AURORA Investigative Center
state: Texas
city: El Paso
country: United States
facility: AURORA Investigative Center
state: Texas
city: El Paso
country: United States
facility: AURORA Investigative Center
state: Texas
city: Houston
country: United States
facility: AURORA Investigative Center
state: Texas
city: Arlington
country: United States
facility: AURORA Investigative Center
state: Virginia
city: Richmond
country: United States
facility: AURORA
state: Virginia
city: Buenos Aires
country: Argentina
facility: AURORA Investigative Center
city: Caba
country: Argentina
facility: AURORA Investigative Center
city: Córdoba
country: Argentina
facility: AURORA Investigative Center
city: La Plata
country: Argentina
facility: AURORA Investigative Center
city: San Miguel De Tucumán
country: Argentina
facility: AURORA Investigative Center
city: Minsk
country: Belarus
facility: AURORA Investigative Cener
city: Minsk
country: Belarus
facility: AURORA Investigative Center
city: Vitebsk
country: Belarus
facility: AURORA Investigative Center
city: Curitiba
country: Brazil
facility: AURORA Investigative Center
city: Porto Alegre
country: Brazil
facility: AURORA Investigative Center
city: Salvador
country: Brazil
facility: AURORA Investigative Center
city: São Paulo
country: Brazil
facility: AURORA Investigative Center
city: Plovdiv
country: Bulgaria
facility: AURORA Investigative Center
city: Smolyan
country: Bulgaria
facility: AURORA Investigative Center
city: Sofia
country: Bulgaria
facility: AURORA Investigative Center
city: Stara Zagora
country: Bulgaria
facility: AURORA Investigative Center
city: Vidin
country: Bulgaria
facility: AURORA Investigative Center
city: Edmonton
country: Canada
facility: AURORA Investigative Center
state: Alberta
city: Montreal
country: Canada
facility: AURORA Investigative Center
state: Quebec
city: Montréal
country: Canada
facility: AURORA Investigative Center
state: Quebec
city: Toronto
country: Canada
facility: AURORA Investigative Center
city: Santiago
country: Chile
facility: AURORA Investigative Center
city: Temuco
country: Chile
facility: AURORA Investigative Center
city: Valdivia
country: Chile
facility: AURORA Investigative Center
city: Barranquilla
country: Colombia
facility: AURORA Investigative Center
city: Bogotá
country: Colombia
facility: AURORA Investigative Center
city: Bucaramanga
country: Colombia
facility: AURORA Investigative Center
city: Zipaquirá
country: Colombia
facility: AURORA Investigative Center
city: San José
country: Costa Rica
facility: AURORA Investigative Center
city: San José
country: Costa Rica
facility: AURORA Investigative Center
city: Osijek
country: Croatia
facility: AURORA Investigative Center
city: Zagreb
country: Croatia
facility: AURORA Investigative Center
city: Santiago de los Caballeros
country: Dominican Republic
facility: AURORA Investigative Center
city: Santo Domingo
country: Dominican Republic
facility: AURORA Investigative Center
city: Guatemala City
country: Guatemala
facility: AURORA Investigative Center
city: Kita
country: Japan
facility: AURORA Investigative Center
state: Osaka
city: Chiba
country: Japan
facility: AURORA Investigative Center
city: Hiroshima
country: Japan
facility: AURORA Investigative Center
city: Ishikawa
country: Japan
facility: AURORA Investigative Center
city: Kitakyushu
country: Japan
facility: AURORA Investigative Center
city: Kita
country: Japan
facility: AURORA Investigative Center
city: Maebashi
country: Japan
facility: AURORA Investigative Center
city: Nagasaki
country: Japan
facility: AURORA Investigative Center
city: Niigata
country: Japan
facility: AURORA Investigative Center
city: Sapporo
country: Japan
facility: AURORA Investigative Center
city: Sendai
country: Japan
facility: AURORA Investigative Center
city: Tokyo
country: Japan
facility: AURORA Investigative Center
city: Daejeon
country: Korea, Republic of
facility: AURORA Investigative Center
city: Seoul
country: Korea, Republic of
facility: AURORA Investigative Center
city: Suwon-si
country: Korea, Republic of
facility: AURORA Investigative Center
city: Wŏnju
country: Korea, Republic of
facility: AURORA Investigative Center
city: Kuala Lumpur
country: Malaysia
facility: AURORA Investigative Center
city: Baja California
country: Mexico
facility: AURORA Investigative Center
city: Coahuila
country: Mexico
facility: AURORA Investigative Center
city: Guadalajara
country: Mexico
facility: AURORA Investigative Center
city: León
country: Mexico
facility: AURORA Investigative Center
city: Mexico City
country: Mexico
facility: AURORA Investigative Center
city: Monclova
country: Mexico
facility: AURORA Investigative Center
city: Mérida
country: Mexico
facility: AURORA Investigative Center
city: Oaxaca
country: Mexico
facility: AURORA Investigative Center
city: San Luis Potosí
country: Mexico
facility: AURORA Investigative Center
city: Sinaloa
country: Mexico
facility: AURORA Investigative Center
city: Amsterdam
country: Netherlands
facility: AURORA Investigative Center
city: Groningen
country: Netherlands
facility: AURORA Investigative Center
city: Leiden
country: Netherlands
facility: AURORA Investigative Center
city: Maastricht
country: Netherlands
facility: AURORA Investigative Center
city: Rotterdam
country: Netherlands
facility: AURORA Investigative Center
city: Skopje
country: North Macedonia
facility: AURORA Investigative Center
city: Lima
country: Peru
facility: AURORA Investigative Center
city: Trujillo
country: Peru
facility: AURORA Investigative Center
city: Angeles City
country: Philippines
facility: AURORA Investigative Center
city: Davao City
country: Philippines
facility: AURORA Investigative Center
city: Lipa
country: Philippines
facility: AURORA Investigative Center
city: Manila
country: Philippines
facility: AURORA Investigative Center
city: Quezon City
country: Philippines
facility: AURORA Investigative Center
city: Katowice
country: Poland
facility: AURORA Investigative Center
city: Warszawa
country: Poland
facility: AURORA Investigative Center
city: Wrocław
country: Poland
facility: AURORA Investigative Center
city: San Juan
country: Puerto Rico
facility: AURORA Investigative Center
city: Kazan
country: Russian Federation
facility: AURORA Investigative Center
city: Kemerovo
country: Russian Federation
facility: AURORA Investigative Center
city: Krasnoyarsk
country: Russian Federation
facility: AURORA Investigative Center
city: Moscow
country: Russian Federation
facility: AURORA Investigative Center
city: Omsk
country: Russian Federation
facility: AURORA Investigative Center
city: Petrozavodsk
country: Russian Federation
facility: AURORA Investigative Center
city: Rostov-on-Don
country: Russian Federation
facility: AURORA Investigative Center
city: Saint Petersburg
country: Russian Federation
facility: AURORA Investigative Center
city: Saint Petersburg
country: Russian Federation
facility: AURORA Investigative Center
city: Samara
country: Russian Federation
facility: AURORA Investigative Center
city: Saratov
country: Russian Federation
facility: AURORA Investigative Center
city: Tol'yatti
country: Russian Federation
facility: AURORA Investigative Center
city: Yaroslavl
country: Russian Federation
facility: AURORA Investigative Center
city: Yekaterinburg
country: Russian Federation
facility: AURORA Investigative Center
city: Belgrade
country: Serbia
facility: AURORA Investigative Center
city: Niš
country: Serbia
facility: AURORA Investigative Center
city: Cape town
country: South Africa
facility: AURORA Investigative Center
city: Johannesburg
country: South Africa
facility: AURORA Investigative Center
city: Pretoria
country: South Africa
facility: AURORA Investigative Center
city: Stellenbosch
country: South Africa
facility: AURORA Investigative Center
city: A Coruña
country: Spain
facility: AURORA Investigative Center
city: Barcelona
country: Spain
facility: AURORA Investigative Center
city: Madrid
country: Spain
facility: AURORA Investigative Center
city: Madrid
country: Spain
facility: AURORA Investigative Center
city: Valencia
country: Spain
facility: AURORA Investigative Center
city: Chang Hua
country: Taiwan
facility: AURORA Investigative Center
city: Chang-hua
country: Taiwan
facility: AURORA Investigative Center
city: Taichung
country: Taiwan
facility: AURORA Investigative Center
city: Taoyuan
country: Taiwan
facility: AURORA Investigative Center
city: Bangkok
country: Thailand
facility: AURORA Investigative Center
city: Chiang Mai
country: Thailand
facility: AURORA Investigative Center
city: Songkhla
country: Thailand
facility: AURORA Investigative Center
city: Balcalı
country: Turkey
facility: AURORA Investigative Center
city: Bursa
country: Turkey
facility: AURORA Investigative Center
city: Efeler
country: Turkey
facility: AURORA Investigative Center
city: Fatih
country: Turkey
facility: AURORA Investigative Center
city: İstanbul
country: Turkey
facility: AURORA Investigative Center
city: Konyaalti
country: Turkey
facility: AURORA Investigative Center
city: Malatya
country: Turkey
facility: AURORA Investigative Center
city: Yenimahalle
country: Turkey
facility: AURORA Investigative Center
city: Kharkiv
country: Ukraine
facility: AURORA Investigative Center
city: Kyiv
country: Ukraine
facility: AURORA Investigative Center
city: Kyiv
country: Ukraine
facility: AURORA Investigative Center
city: Luts'k
country: Ukraine
facility: AURORA Investigative Center
city: Odessa
country: Ukraine
facility: AURORA Investigative Center
city: Vinnytsya
country: Ukraine
facility: AURORA Investigative Center
city: Zaporizhzhya
country: Ukraine
facility: AURORA Investigative Center
city: Hanoi
country: Vietnam
facility: AURORA Investigative Center
city: Ho Chi Minh City
country: Vietnam
facility: AURORA Investigative Center
Study officials:
affiliation: Ohio State University
name: Samir Parikh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Ling 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.
citation: Ling 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.
citation: Mayo 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.
citation: Dooley 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.
citation: Busque 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.
citation: Rovin 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.