Clinical trial NCT02141672: AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Nephritis
Keywords: lupus nephritis
calcineurin inhibitors
voclosporin
Lead sponsor: Aurinia Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2014-05-19
Enrollment: 265
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: 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.

Detailed description: Voclosporin is a next generation CNI intended for use in the prevention of organ graft rejection and for the treatment of autoimmune diseases. The aim of the current study is to investigate whether voclosporin added to the standard of care treatment in active LN is able to reduce disease activity, as measured by a reduction in proteinuria. Two doses of voclosporin will be studied and compared in a placebo controlled trial on a background of MMF and corticosteroids. Patients with active, flaring LN will be eligible to enter the study. They are required to have a diagnosis of LN according to established diagnostic criteria (American College of Rheumatology) and clinical and biopsy features suggestive of active nephritis. Efficacy will be assessed by the ability of the drug combination to reduce the level of proteinuria while demonstrating an acceptable safety profile.

Eligibility criteria: Inclusion Criteria:

Male or female subjects aged 18 to 75 years.

Diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria.

Kidney biopsy within 6 months prior to Screening (Visit 1) with a histologic diagnosis of lupus nephritis (International Society of Nephrology/Renal Pathology Society 2003 classification of lupus nephritis) Classes III, IV-S or IV-G, (A) or (A/C); or Class V, alone or in combination with Class III or IV.

Laboratory evidence of active nephritis at screening, defined as:

* Class III, IV-S or IV-G: Confirmed proteinuria ≥1,500 mg/24 hours when assessed by 24 hour urine collection, defined by a UPCR of ≥1.5 mg/mg assessed in a first morning void urine specimen (2 samples).
* Class V (alone or in combination with Class III or IV): Confirmed proteinuria ≥2,000 mg/24 hours when assessed by 24 hour urine collection, defined by a UPCR of ≥2 mg/mg assessed in a first morning void urine specimen (2 samples).

Exclusion Criteria:

Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ≤45 mL/min/1.73 m2.

Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.

A previous kidney transplant or planned transplant within study treatment period.

In the opinion of the Investigator, subject does not require long-term immunosuppressive treatment (in addition to corticosteroids).

Current or medical history of:

* Pancreatitis or gastrointestinal hemorrhage within 6 months prior to screening.
* Active unhealed peptic ulcer within 3 months prior to screening. If an ulcer has healed and the subject is on adequate therapy, the subject may be randomized.
* Congenital or acquired immunodeficiency.
* Clinically significant drug or alcohol abuse 2 years prior to screening.
* Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia 1, but have been treated with conization or loop electrosurgical excision procedure, and have had a normal repeat PAP are allowed.
* Lymphoproliferative disease or previous total lymphoid irradiation.
* Severe viral infection (such as CMV, HBV, HCV) within 3 months of screening; or known human immunodeficiency virus infection.
* Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid.

Other known clinically significant active medical conditions, such as:

* Severe cardiovascular disease including congestive heart failure, history of cardiac dysrhythmia or congenital long QT syndrome.
* Liver dysfunction (aspartate aminotransferase, alanine aminotransferase, or bilirubin greater than 2.5 times the upper limit of normal) at screening and confirmed before randomization.
* Chronic obstructive pulmonary disease or asthma requiring oral steroids.
* Bone marrow insufficiency unrelated to active SLE (according to Investigator judgment) with white blood cell count \<2,500/mm3; absolute neutrophil count \<1.3 x 103/μL; thrombocytopenia (platelet count \<50,000/mm3).
* Active bleeding disorders.
* Current infection requiring IV antibiotics.

Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes. Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes are not excluded.

Subjects who are pregnant, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions.

Primary outcomes:
measure: Number of Subjects Achieving Complete Renal Remission at 24 Weeks
timeFrame: week 24
Secondary outcomes:
measure: Number of Subjects Achieving Complete Renal Remission at 48 Weeks
timeFrame: Week 48
measure: Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids
timeFrame: Weeks 24 and 48
measure: Time to Complete Remission (Number of Weeks)
timeFrame: week 48
measure: Time to Sustained Early Complete Remission (Number of Weeks)
timeFrame: week 48
measure: Number of Subjects Achieving Sustained Early Complete Remission
timeFrame: week 48
measure: Time to Partial Remission (Number of Weeks)
timeFrame: week 48
measure: Number of Subjects Achieving Partial Remission
timeFrame: week 48
measure: Number of Subjects Achieving, and Remaining in, Complete Remission
timeFrame: week 48
measure: Duration of Complete Remission (Number of Weeks)
timeFrame: week 48
measure: Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks
timeFrame: week 24 and 48
measure: Time to Sustained Partial Remission (Number of Weeks)
timeFrame: week 48
measure: Number of Subjects Achieving Sustained Partial Remission
timeFrame: week 48
measure: Time to Sustained Early Partial Remission (Number of Weeks)
timeFrame: week 48
measure: Number of Subjects Achieving Sustained Early Partial Remission
timeFrame: week 48
measure: Change From Baseline in UPCR at Weeks 24 and 48
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score
timeFrame: Baseline, Week 24 and Week 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: AURA-LV Site
state: California
city: Palo Alto
country: United States
facility: AURA-LV Site
state: California
city: Gainesville
country: United States
facility: AURA-LV Site
state: Florida
city: Miami
country: United States
facility: AURA-LV Site
state: Florida
city: Farmington Hills
country: United States
facility: AURA-LV Site
state: Michigan
city: Brooklyn
country: United States
facility: AURA-LV Site
state: New York
city: New York
country: United States
facility: AURA-LV Site
state: New York
city: Chapel Hill
country: United States
facility: AURA-LV Site
state: North Carolina
city: Charlotte
country: United States
facility: AURA-LV Site
state: North Carolina
city: Columbus
country: United States
facility: AURA-LV Site
state: Ohio
city: Hershey
country: United States
facility: AURA-LV Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: AURA-LV Site
state: Tennessee
city: Dallas
country: United States
facility: AURA-LV Site
state: Texas
city: Houston
country: United States
facility: AURA-LV Site
state: Texas
city: Dhaka
country: Bangladesh
facility: AURA-LV Site
city: Dhaka
country: Bangladesh
facility: AURA-LV Site
city: Minsk
country: Belarus
facility: AURA-LV Site
city: Minsk
country: Belarus
facility: AURA-LV Site
city: Minsk
country: Belarus
facility: AURA-LV Site
city: Vitebsk
country: Belarus
facility: AURA-LV Site
city: Plovdiv
country: Bulgaria
facility: AURA-L Site
city: Sofia
country: Bulgaria
facility: AURA-LV Site
city: Sofia
country: Bulgaria
facility: AURA-LV Site
city: Varna
country: Bulgaria
facility: AURA-LV Site
city: Hong Kong
country: China
facility: AURA-LV Site
city: Guayaquil
country: Ecuador
facility: AURA-LV Site
city: Quito
country: Ecuador
facility: AURA-LV Site
city: Tbilisi
country: Georgia
facility: AURA-LV Site
city: Tbilisi
country: Georgia
facility: AURA-LV Site
city: Guatemala City
country: Guatemala
facility: AURA-LV Site
city: Busan
country: Korea, Republic of
facility: AURA-LV Site
city: Daegu
country: Korea, Republic of
facility: AURA -LV Site
city: Seoul
country: Korea, Republic of
facility: AURA-LV Site
city: Seoul
country: Korea, Republic of
facility: AURA-LV Site
city: Wonju
country: Korea, Republic of
facility: AURA-LV Site
city: Guadalajara
country: Mexico
facility: AURA-LV Site
city: Mexicali
country: Mexico
facility: AURA-LV Site
city: Oaxaca
country: Mexico
facility: AURA-LV Site
city: Tlalpan
country: Mexico
facility: AURA-LV Site
city: Tlalpan
country: Mexico
facility: AURA-LV Site
city: Angeles City
country: Philippines
facility: AURA-LV Site
city: Batangas
country: Philippines
facility: AURA-LV Site
city: Cebu city
country: Philippines
facility: AURA-LV Site
city: Davao City
country: Philippines
facility: AURA-LV Site
city: Manila
country: Philippines
facility: AURA-LV Site
city: Manila
country: Philippines
facility: AURA-LV Site
city: Manila
country: Philippines
facility: AURA-LV Site
city: Quezon City
country: Philippines
facility: AURA-LV Site
city: Katowice
country: Poland
facility: AURA-LV Site
city: Radom
country: Poland
facility: AURA-LV Site
city: Warsaw
country: Poland
facility: AURA-LV Site
city: Wroclaw
country: Poland
facility: AURA-LV Site
city: Kazan
country: Russian Federation
facility: AURA-LV Site
city: Kemerovo
country: Russian Federation
facility: AURA-LV Site
city: Kemerovo
country: Russian Federation
facility: AURA-LV Site
city: Moscow
country: Russian Federation
facility: AURA-LV Site
city: Moscow
country: Russian Federation
facility: AURA-LV Site
city: Omsk
country: Russian Federation
facility: AURA-LV Site
city: Orenburg
country: Russian Federation
facility: AURA-LV Site
city: Petrozavodsk
country: Russian Federation
facility: AURA-LV Site
city: Rostov-on-Don
country: Russian Federation
facility: AURA-LV Site
city: Saratov
country: Russian Federation
facility: AURA-LV Site
city: St. Petersburg
country: Russian Federation
facility: AURA-LV Site
city: St. Petersburg
country: Russian Federation
facility: AURA-LV Site
city: St. Petersburg
country: Russian Federation
facility: AURA-LV Site
city: Togliatti
country: Russian Federation
facility: AURA-LV Site
city: Yaroslavl
country: Russian Federation
facility: AURA-LV Site
city: Belgrade
country: Serbia
facility: AURA-LV Site
city: Nis
country: Serbia
facility: AURA-LV Site
city: Singapore
country: Singapore
facility: AURA-LV Site
city: Singapore
country: Singapore
facility: AURA-LV Site
city: Barcelona
country: Spain
facility: AURA-LV Site
city: Madrid
country: Spain
facility: AURA-LV
city: Colombo
country: Sri Lanka
facility: AURA-LV Site
city: Kandy
country: Sri Lanka
facility: AUR-LV Site
city: Nugegoda
country: Sri Lanka
facility: AURA-LV Site
city: Ragama
country: Sri Lanka
facility: AURA-LV Site
city: Kaohsiung City
country: Taiwan
facility: AURA-LV Site
city: Taoyuan City
country: Taiwan
facility: AURA-LV Site
city: Bangkok
country: Thailand
facility: AURA-LV Site
city: Chiang Mai
country: Thailand
facility: AURA-LV Site
city: Kharkiv
country: Ukraine
facility: AURA-LV Site
city: Kyiv
country: Ukraine
facility: AURA-LV Site
city: Kyiv
country: Ukraine
facility: AURA-LV Site
city: Lutsk
country: Ukraine
facility: AURA-LV Site
city: Zaporizhzhya
country: Ukraine
facility: AURA-LV Site
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Mary Anne Dooley, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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: Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li LS, Mysler E, Sanchez-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.