Overview

This trial is active, not recruiting.

Condition lupus nephritis
Treatments voclosporin high dose, voclosporin low dose, placebo
Phase phase 2
Sponsor Aurinia Pharmaceuticals Inc.
Start date June 2014
End date July 2016
Trial size 258 participants
Trial identifier NCT02141672, AUR-VCS2012-01

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Voclosporin, oral, 23.7 mg BID
voclosporin low dose ISA247
(Experimental)
Voclosporin, oral 23.7 mg BID until Week 2, then voclosporin, oral, 39.5 mg BID
voclosporin high dose ISA247
(Placebo Comparator)
Low dose: Voclosporin placebo, oral, 3 capsules BID High dose: Voclosporin placebo, oral, 3 capsules BID until Week 2 then voclosporin placebo, oral, 5 capsules BID
placebo

Primary Outcomes

Measure
The number of subjects achieving complete remission at 24 Weeks
time frame: 24 weeks

Secondary Outcomes

Measure
Complete remission as per the primary endpoint analyzed at Week 48 compared to placebo in subjects with active lupus nephritis.
time frame: Week 48
Complete remission in the presence of low dose steroids at Week 24 and Week 48.
time frame: Weeks 24 and 48
Time to (and proportion achieving) early, sustained complete remission
time frame: 24 Weeks
Time to sustained partial remission
time frame: 48 Weeks
Duration of complete remission (in months)
time frame: 48 Weeks
Complete remission at 48 weeks
time frame: 48 Weeks
Time to complete remission
time frame: 48 weeks
Partial remission
time frame: Weeks 24 and 48
Time to partial remission
time frame: 48 Weeks
Time to (and proportion achieving) early, sustained partial remission
time frame: 48 Weeks
Time to sustained partial remission
time frame: 48 Weeks
Change from baseline in UPCR at Weeks 24 and 48.
time frame: Weeks 24 and 48
Change from baseline in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) - SLEDAI score at Weeks 24 and 48.
time frame: Weeks 24 and 48
Change from baseline in serum creatinine, urine protein, serum albumin, eGFR at each visit measured.
time frame: 50 Weeks
Proportion of subjects with active urinary sediment at each visit measured.
time frame: 50 Weeks
Change from baseline in immunology parameters (C3, C4, and anti-double-stranded deoxyribonucleic acid (dsDNA) and biomarkers at each visit measured.
time frame: 50 Weeks

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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.

Additional Information

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
Principal investigator Mary Anne Dooley, MD, MPH
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Aurinia Pharmaceuticals Inc..