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

Lupus Nephritis Clinical Trial

— AURA-LV  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02141672
• Other study ID #: AUR-VCS-2012-01
• Status: Completed
• Phase: Phase 2
• Start date: June 2014
• Est. completion date: January 2017

Study information

• Verified date: April 2021
• Source: Aurinia Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 265
• Est. completion date: January 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Voclosporin High Dose

• Voclosporin Low Dose

• Placebo

Locations

Country	Name	City	State
Bangladesh	AURA-LV Site	Dhaka
Bangladesh	AURA-LV Site	Dhaka
Belarus	AURA-LV Site	Minsk
Belarus	AURA-LV Site	Minsk
Belarus	AURA-LV Site	Minsk
Belarus	AURA-LV Site	Vitebsk
Bulgaria	AURA-L Site	Plovdiv
Bulgaria	AURA-LV Site	Sofia
Bulgaria	AURA-LV Site	Sofia
Bulgaria	AURA-LV Site	Varna
China	AURA-LV Site	Hong Kong
Ecuador	AURA-LV Site	Guayaquil
Ecuador	AURA-LV Site	Quito
Georgia	AURA-LV Site	Tbilisi
Georgia	AURA-LV Site	Tbilisi
Guatemala	AURA-LV Site	Guatemala City
Korea, Republic of	AURA-LV Site	Busan
Korea, Republic of	AURA -LV Site	Daegu
Korea, Republic of	AURA-LV Site	Seoul
Korea, Republic of	AURA-LV Site	Seoul
Korea, Republic of	AURA-LV Site	Wonju
Mexico	AURA-LV Site	Guadalajara
Mexico	AURA-LV Site	Mexicali
Mexico	AURA-LV Site	Oaxaca
Mexico	AURA-LV Site	Tlalpan
Mexico	AURA-LV Site	Tlalpan
Philippines	AURA-LV Site	Angeles City
Philippines	AURA-LV Site	Batangas
Philippines	AURA-LV Site	Cebu city
Philippines	AURA-LV Site	Davao City
Philippines	AURA-LV Site	Manila
Philippines	AURA-LV Site	Manila
Philippines	AURA-LV Site	Manila
Philippines	AURA-LV Site	Quezon City
Poland	AURA-LV Site	Katowice
Poland	AURA-LV Site	Radom
Poland	AURA-LV Site	Warsaw
Poland	AURA-LV Site	Wroclaw
Russian Federation	AURA-LV Site	Kazan
Russian Federation	AURA-LV Site	Kemerovo
Russian Federation	AURA-LV Site	Kemerovo
Russian Federation	AURA-LV Site	Moscow
Russian Federation	AURA-LV Site	Moscow
Russian Federation	AURA-LV Site	Omsk
Russian Federation	AURA-LV Site	Orenburg
Russian Federation	AURA-LV Site	Petrozavodsk
Russian Federation	AURA-LV Site	Rostov-on-Don
Russian Federation	AURA-LV Site	Saratov
Russian Federation	AURA-LV Site	St. Petersburg
Russian Federation	AURA-LV Site	St. Petersburg
Russian Federation	AURA-LV Site	St. Petersburg
Russian Federation	AURA-LV Site	Togliatti
Russian Federation	AURA-LV Site	Yaroslavl
Serbia	AURA-LV Site	Belgrade
Serbia	AURA-LV Site	Nis
Singapore	AURA-LV Site	Singapore
Singapore	AURA-LV Site	Singapore
Spain	AURA-LV Site	Barcelona
Spain	AURA-LV	Madrid
Sri Lanka	AURA-LV Site	Colombo
Sri Lanka	AUR-LV Site	Kandy
Sri Lanka	AURA-LV Site	Nugegoda
Sri Lanka	AURA-LV Site	Ragama
Taiwan	AURA-LV Site	Kaohsiung City
Taiwan	AURA-LV Site	Taoyuan City
Thailand	AURA-LV Site	Bangkok
Thailand	AURA-LV Site	Chiang Mai
Ukraine	AURA-LV Site	Kharkiv
Ukraine	AURA-LV Site	Kyiv
Ukraine	AURA-LV Site	Kyiv
Ukraine	AURA-LV Site	Lutsk
Ukraine	AURA-LV Site	Zaporizhzhya
United States	AURA-LV Site	Brooklyn	New York
United States	AURA-LV Site	Chapel Hill	North Carolina
United States	AURA-LV Site	Charlotte	North Carolina
United States	AURA-LV Site	Chattanooga	Tennessee
United States	AURA-LV Site	Columbus	Ohio
United States	AURA-LV Site	Dallas	Texas
United States	AURA-LV Site	Farmington Hills	Michigan
United States	AURA-LV Site	Gainesville	Florida
United States	AURA-LV Site	Hershey	Pennsylvania
United States	AURA-LV Site	Houston	Texas
United States	AURA-LV Site	Los Angeles	California
United States	AURA-LV Site	Miami	Florida
United States	AURA-LV Site	New York	New York
United States	AURA-LV Site	Palo Alto	California

Sponsors (1)

Lead Sponsor	Collaborator
Aurinia Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Bangladesh,  Belarus,  Bulgaria,  China,  Ecuador,  Georgia,  Guatemala,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Russian Federation,  Serbia,  Singapore,  Spain,  Sri Lanka,  Taiwan,  Thailand,  Ukraine, 

References & Publications (2)

Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li LS, Mysler E, Sánchez-Guerrero J, Solomons N, Wofsy D; Aspreva Lupus Management Study Group. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009 May;20(5):1103-12. doi: 10.1681/ASN.2008101028. Epub 2009 Apr 15. — 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: 10.1056/NEJMoa1014460. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects Achieving Complete Renal Remission at 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 received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.	week 24
Secondary	Number of Subjects Achieving Complete Renal Remission at 48 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 received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.	Week 48
Secondary	Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids	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 received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.; Low-dose steroids is defined as use of =5 mg prednisone for 8 weeks leading up to the Week 24 visit date or for 12 weeks leading up to the Week 48 visit date.	Weeks 24 and 48
Secondary	Time to Complete Remission (Number of Weeks)	Time to Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR = 0.5mg in the absence of rescue medication.	week 48
Secondary	Time to Sustained Early Complete Remission (Number of Weeks)	Time to Sustained Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR = 0.5mg occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication.	week 48
Secondary	Number of Subjects Achieving Sustained Early Complete Remission	Sustained early complete remission defined as complete remission that occurred on or before Week 24 and was sustained through Week 48	week 48
Secondary	Time to Partial Remission (Number of Weeks)	Time to partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication.	week 48
Secondary	Number of Subjects Achieving Partial Remission	Partial remission is defined as a 50% reduction in UPCR from baseline at Week 24 and Week 48.	week 48
Secondary	Number of Subjects Achieving, and Remaining in, Complete Remission	Sustained complete remission defined as the first occurrence of complete remission that was sustained through Week 48	week 48
Secondary	Duration of Complete Remission (Number of Weeks)	Duration of Complete Remission is defined as time of first occurrence of UPCR = 0.5 mg/mg until the second increase above 0.5 mg/mg (i.e. a single occurrence above 0.5 is permitted) or use of rescue medication.	week 48
Secondary	Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks	Number of patients with partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction at week 24 or week 48 in the absence of rescue medication.	week 24 and 48
Secondary	Time to Sustained Partial Remission (Number of Weeks)	Time to sustained partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication.	week 48
Secondary	Number of Subjects Achieving Sustained Partial Remission	Sustained partial remission defined as the first occurrence of partial remission that was sustained through Week 48	week 48
Secondary	Time to Sustained Early Partial Remission (Number of Weeks)	Time to sustained early partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication.	week 48
Secondary	Number of Subjects Achieving Sustained Early Partial Remission	Early partial remission defined as partial remission that occurred on or before Week 24 and was sustained through Week 48	week 48
Secondary	Change From Baseline in UPCR at Weeks 24 and 48	Change from baseline in urine protein creatinine ratio at weeks 24 and 48	Baseline, Week 24 and Week 48
Secondary	Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score	The SELENA-SLEDAI assesses disease activity within the last 10 days. Twenty-four items are scored for nine organ systems, and summed to a maximum of 105 points. A score of 6 is considered clinically significant and indicates active disease. For analysis purposes, a score =6 was categorized as "high". The 24 items are as follows: 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, and leukopenia.	Baseline, Week 24 and Week 48