Aurinia Renal Response in Active Lupus With Voclosporin

Lupus Nephritis Clinical Trial

— AURORA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03021499
• Other study ID #: AUR-VCS-2016-01
• Status: Completed
• Phase: Phase 3
• Start date: May 17, 2017
• Est. completion date: October 10, 2019

Study information

• Verified date: March 2023
• Source: Aurinia Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 358
• Est. completion date: October 10, 2019
• Est. primary completion date: September 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Voclosporin
calcineurin inhibitor
• Placebo Oral Capsule
matching placebo capsule

Locations

Country	Name	City	State
Argentina	AURORA Investigative Center	Buenos Aires
Argentina	AURORA Investigative Center	Caba
Argentina	AURORA Investigative Center	Córdoba
Argentina	AURORA Investigative Center	La Plata
Argentina	AURORA Investigative Center	San Miguel De Tucumán
Belarus	AURORA Investigative Cener	Minsk
Belarus	AURORA Investigative Center	Minsk
Belarus	AURORA Investigative Center	Vitebsk
Brazil	AURORA Investigative Center	Curitiba
Brazil	AURORA Investigative Center	Porto Alegre
Brazil	AURORA Investigative Center	Salvador
Brazil	AURORA Investigative Center	São Paulo
Bulgaria	AURORA Investigative Center	Plovdiv
Bulgaria	AURORA Investigative Center	Smolyan
Bulgaria	AURORA Investigative Center	Sofia
Bulgaria	AURORA Investigative Center	Stara Zagora
Bulgaria	AURORA Investigative Center	Vidin
Canada	AURORA Investigative Center	Edmonton	Alberta
Canada	AURORA Investigative Center	Montreal	Quebec
Canada	AURORA Investigative Center	Montréal	Quebec
Canada	AURORA Investigative Center	Toronto
Chile	AURORA Investigative Center	Santiago
Chile	AURORA Investigative Center	Temuco
Chile	AURORA Investigative Center	Valdivia
Colombia	AURORA Investigative Center	Barranquilla
Colombia	AURORA Investigative Center	Bogotá
Colombia	AURORA Investigative Center	Bucaramanga
Colombia	AURORA Investigative Center	Zipaquirá
Costa Rica	AURORA Investigative Center	San José
Costa Rica	AURORA Investigative Center	San José
Croatia	AURORA Investigative Center	Osijek
Croatia	AURORA Investigative Center	Zagreb
Dominican Republic	AURORA Investigative Center	Santiago de los Caballeros
Dominican Republic	AURORA Investigative Center	Santo Domingo
Guatemala	AURORA Investigative Center	Guatemala City
Japan	AURORA Investigative Center	Chiba
Japan	AURORA Investigative Center	Hiroshima
Japan	AURORA Investigative Center	Ishikawa
Japan	AURORA Investigative Center	Kita
Japan	AURORA Investigative Center	Kita	Osaka
Japan	AURORA Investigative Center	Kitakyushu
Japan	AURORA Investigative Center	Maebashi
Japan	AURORA Investigative Center	Nagasaki
Japan	AURORA Investigative Center	Niigata
Japan	AURORA Investigative Center	Sapporo
Japan	AURORA Investigative Center	Sendai
Japan	AURORA Investigative Center	Tokyo
Korea, Republic of	AURORA Investigative Center	Daejeon
Korea, Republic of	AURORA Investigative Center	Seoul
Korea, Republic of	AURORA Investigative Center	Suwon-si
Korea, Republic of	AURORA Investigative Center	Wonju
Malaysia	AURORA Investigative Center	Kuala Lumpur
Mexico	AURORA Investigative Center	Baja California
Mexico	AURORA Investigative Center	Coahuila
Mexico	AURORA Investigative Center	Guadalajara
Mexico	AURORA Investigative Center	León
Mexico	AURORA Investigative Center	Mérida
Mexico	AURORA Investigative Center	Mexico City
Mexico	AURORA Investigative Center	Monclova
Mexico	AURORA Investigative Center	Oaxaca
Mexico	AURORA Investigative Center	San Luis Potosí
Mexico	AURORA Investigative Center	Sinaloa
Netherlands	AURORA Investigative Center	Amsterdam
Netherlands	AURORA Investigative Center	Groningen
Netherlands	AURORA Investigative Center	Leiden
Netherlands	AURORA Investigative Center	Maastricht
Netherlands	AURORA Investigative Center	Rotterdam
North Macedonia	AURORA Investigative Center	Skopje
Peru	AURORA Investigative Center	Lima
Peru	AURORA Investigative Center	Trujillo
Philippines	AURORA Investigative Center	Angeles City
Philippines	AURORA Investigative Center	Davao City
Philippines	AURORA Investigative Center	Lipa
Philippines	AURORA Investigative Center	Manila
Philippines	AURORA Investigative Center	Quezon City
Poland	AURORA Investigative Center	Katowice
Poland	AURORA Investigative Center	Warszawa
Poland	AURORA Investigative Center	Wroclaw
Puerto Rico	AURORA Investigative Center	San Juan
Russian Federation	AURORA Investigative Center	Kazan
Russian Federation	AURORA Investigative Center	Kemerovo
Russian Federation	AURORA Investigative Center	Krasnoyarsk
Russian Federation	AURORA Investigative Center	Moscow
Russian Federation	AURORA Investigative Center	Omsk
Russian Federation	AURORA Investigative Center	Petrozavodsk
Russian Federation	AURORA Investigative Center	Rostov-on-Don
Russian Federation	AURORA Investigative Center	Saint Petersburg
Russian Federation	AURORA Investigative Center	Saint Petersburg
Russian Federation	AURORA Investigative Center	Samara
Russian Federation	AURORA Investigative Center	Saratov
Russian Federation	AURORA Investigative Center	Tol'yatti
Russian Federation	AURORA Investigative Center	Yaroslavl
Russian Federation	AURORA Investigative Center	Yekaterinburg
Serbia	AURORA Investigative Center	Belgrade
Serbia	AURORA Investigative Center	Niš
South Africa	AURORA Investigative Center	Cape town
South Africa	AURORA Investigative Center	Johannesburg
South Africa	AURORA Investigative Center	Pretoria
South Africa	AURORA Investigative Center	Stellenbosch
Spain	AURORA Investigative Center	A Coruña
Spain	AURORA Investigative Center	Barcelona
Spain	AURORA Investigative Center	Madrid
Spain	AURORA Investigative Center	Madrid
Spain	AURORA Investigative Center	Valencia
Taiwan	AURORA Investigative Center	Chang Hua
Taiwan	AURORA Investigative Center	Chang-hua
Taiwan	AURORA Investigative Center	Taichung
Taiwan	AURORA Investigative Center	Taoyuan
Thailand	AURORA Investigative Center	Bangkok
Thailand	AURORA Investigative Center	Chiang Mai
Thailand	AURORA Investigative Center	Songkhla
Turkey	AURORA Investigative Center	Balcali
Turkey	AURORA Investigative Center	Bursa
Turkey	AURORA Investigative Center	Efeler
Turkey	AURORA Investigative Center	Fatih
Turkey	AURORA Investigative Center	Istanbul
Turkey	AURORA Investigative Center	Konyaalti
Turkey	AURORA Investigative Center	Malatya
Turkey	AURORA Investigative Center	Yenimahalle
Ukraine	AURORA Investigative Center	Kharkiv
Ukraine	AURORA Investigative Center	Kyiv
Ukraine	AURORA Investigative Center	Kyiv
Ukraine	AURORA Investigative Center	Luts'k
Ukraine	AURORA Investigative Center	Odessa
Ukraine	AURORA Investigative Center	Vinnytsya
Ukraine	AURORA Investigative Center	Zaporizhzhya
United States	AURORA Investigative Center	Arlington	Virginia
United States	AURORA Investigative Center	Atlanta	Georgia
United States	AURORA Investigative Center	Aurora	Colorado
United States	AURORA Investigative Center	Baton Rouge	Louisiana
United States	AURORA Investigative Center	Beaumont	Texas
United States	AURORA Investigative Center	Beverly Hills	California
United States	AURORA Investigative Center	Boston	Massachusetts
United States	AURORA Investigative Center	Chapel Hill	North Carolina
United States	AURORA Investigative Center	Charleston	South Carolina
United States	AURORA Investigative Center	Charlotte	North Carolina
United States	AURORA Investigative Center	Charlotte	North Carolina
United States	AURORA Investigative Center	Chattanooga	Tennessee
United States	AURORA Investigative Center	Chicago	Illinois
United States	AURORA Investigative Center	Clearwater	Florida
United States	AURORA Investigative Center	Cleveland	Ohio
United States	AURORA Investigative Center	Columbus	Ohio
United States	AURORA Investigative Center	Columbus	Georgia
United States	AURORA Investigative Center	Dallas	Texas
United States	AURORA Investigative Center	Dallas	Texas
United States	AURORA Investigative Center	Dallas	Texas
United States	AURORA Investigative Center	DeBary	Florida
United States	AURORA Investigative Center	Denver	Colorado
United States	AURORA Investigative Center	Detroit	Michigan
United States	AURORA Investigative Center	El Paso	Texas
United States	AURORA Investigative Center	El Paso	Texas
United States	AURORA Investigative Center	Fort Lauderdale	Florida
United States	AURORA Investigative Center	Fort Myers	Florida
United States	AURORA Investigative Center	Grand Blanc	Michigan
United States	AURORA Investigative Center	Great Neck	New York
United States	AURORA Investigative Center	Greenville	North Carolina
United States	AURORA Investigative Center	Hendersonville	Tennessee
United States	AURORA Investigative Center	Houston	Texas
United States	AURORA Investigative Center	Huntsville	Alabama
United States	AURORA Investigative Center	Las Vegas	Nevada
United States	AURORA Investigative Center	Lawrenceville	Georgia
United States	AURORA Investigative Center	Los Angeles	California
United States	AURORA Investigative Center	Los Angeles	California
United States	AURORA Investigative Center	Louisville	Kentucky
United States	AURORA Investigative Center	Miami	Florida
United States	AURORA Investigative Center	New Bern	North Carolina
United States	AURORA Investigative Center	New Haven	Connecticut
United States	AURORA Investigative Center	New Orleans	Louisiana
United States	AURORA Investigative Center	New York	New York
United States	AURORA Investigative Center	New York	New York
United States	AURORA Investigative Center	New York	New York
United States	AURORA Investigative Center	Newark	New Jersey
United States	AURORA Investigative Center	Oklahoma City	Oklahoma
United States	AURORA Investigative Center	Oklahoma City	Oklahoma
United States	AURORA Investigative Center	Orlando	Florida
United States	AURORA Investigative Center	Palo Alto	California
United States	AURORA Investigative Center	Phoenix	Arizona
United States	AURORA Investigative Center	Phoenix	Arizona
United States	AURORA	Richmond	Virginia
United States	AURORA Investigative Center	Rochester	Minnesota
United States	AURORA Investigative Center	Saint Louis	Missouri
United States	AURORA Investigative Center	Syracuse	New York
United States	AURORA Investigative Center	Thousand Oaks	California
United States	AURORA Investigative Center	Torrance	California
United States	AURORA Investigative Center	Winter Park	Florida
Vietnam	AURORA Investigative Center	Hanoi
Vietnam	AURORA Investigative Center	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
Aurinia Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Belarus,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Costa Rica,  Croatia,  Dominican Republic,  Guatemala,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  North Macedonia,  Peru,  Philippines,  Poland,  Puerto Rico,  Russian Federation,  Serbia,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine, 

References & Publications (6)

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. — View 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: 1 — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	52 Weeks
Secondary	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	52 Weeks
Secondary	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.	52 Weeks
Secondary	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.	Week 24
Secondary	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.	Weeks 24 and 52
Secondary	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)	Week 52
Secondary	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	Week 52
Secondary	Number of Subjects Achieving 50% Reduction in Urine Protein Creatinine Ratio	Number of subjects achieving 50% reduction in Urine Protein Creatinine ratio	52 Weeks
Secondary	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.	52 weeks
Secondary	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	Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Secondary	Change From Baseline in UPCR	Change from baseline by visit in Urine Protein Creatinine Ratio. Baseline is the average of two pre-randomisation values.	Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Secondary	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	Week 24 and Week 52
Secondary	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.	Week 24 and Week 52
Secondary	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.	Week 24 and Week 52