Active lupus nephritis MedDRA version: 17.0 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: Voclosporin
Product Code: ISA247
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Voclosporin
CAS Number: 515814-01-4
Current Sponsor code: ISA247
Other descriptive name: VOCLOSPO
Sponsors
Aurinia Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent (by subject or legally acceptable representative) before any study-specific procedures are performed. 2. Male or female subjects aged 18 to 75 years inclusive at the time of consent. 3. Diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria (1997; see Appendix 7). 4. Kidney biopsy within 6 months prior to screening (Visit 1) with a histologic diagnosis of lupus nephritis International Society of Nephrology/Renal Pathology Society Classes III, IV-S or IV-G, (A) or (A/C); or Class V, alone or in combination with Class III or IV; see Appendix 5. 5. Laboratory evidence of active nephritis at screening, defined as: ? Class III Confirmed proteinuria ?2,000 mg/24 hours when assessed by 24 hour urine collection, defined by a urine protein/creatinine ratio (UPCR) of ?2 mg/mg assessed in a first morning void urine specimen (2 samples). ? Class IV-S or Class 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). 6. In the opinion of the Investigator, subject requires high dose corticosteroids and immunosuppressive therapy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 222 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Subjects unable or unwilling to give written informed consent and/or to comply with study procedures. 2. Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ?45 mL/min/1.73 m2 at screening (Visit 1) 3. Currently taking or known need for any of the medications listed in Section 7.8, Prohibited Therapy and Concomitant Treatment, page 58. 4. Serum potassium >5.5 mmol/L at screening confirmed before randomization. 5. Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period. 6. A previous kidney transplant or planned transplant within study treatment period. 7. In the opinion of the Investigator, subject does not require long-term immunosuppressive treatment (in addition to corticosteroids). 8. Any known hypersensitivity or contraindication to MMF, mycophenolic acid, cyclosporine, corticosteroids or any components of these drug products. 9. 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. ? In the opinion of the Investigator, 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. 10. 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. QTcF (QT interval duration corrected for heart rate using method of Fridericia) exceeding 480 msec in the presence of a normal QRS interval (<110 msec) at time of screening will result in exclusion. ? 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 × 103/?L; thrombocytopenia (platelet count <50,000/mm3). ? Active bleeding disorders. ? Current infection requiring IV antibiotics. 11. Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes (e.g., scleroderma with significant pulmonary hypertension; any condition for which additional immunosuppression is indicated). Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes (e.g., Sjogren?s syndrome) are not excluded. 12. Other major physical or psychiatric i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? 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 (LN).;Secondary Objective: ? To assess the safety and tolerability of 2 doses of voclosporin over 48 weeks compared to placebo in subjects with active LN. ? To assess the efficacy of 2 doses of voclosporin versus placebo over 48 weeks in subjects with active LN.;Primary end point(s): The number of subjects achieving complete remission at 24 weeks. Complete remission is defined as: Complete remission as defined as: ? Confirmed protein/creatinine ratio of ?0.5 mg/mg, and ? No confirmed decrease from baseline in eGFR of ?20%. Subjects who receive rescue medication for lupus (refer to Section 7.8, Prohibited Therapy and Concomitant Treatment, page 58) or ?10 mg prednisone after Week 16 will not be considered as achieving complete remission.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Complete remission as per the primary endpoint analyzed at Week 48. ? Complete remission in the presence of low dose steroids at Week 24 (defined as confirmed complete remission and ?5 mg prednisone for ?8 weeks) and Week 48 (defined as confirmed complete remission and ?5 mg prednisone for ?12 weeks). ? Time to complete remission. ? Time to (and proportion achieving) early, sustained complete remission (defined as complete remission which occurs on or before Week 24 which is sustained through Week 48). ? Time to sustained complete remission (defined as the first occurrence of complete remission which is sustained through Week 48). ? Duration of complete remission (in months). ? Partial remission as defined by 50% reduction in protein/creatinine ratio from baseline at Weeks 24 and 48. ? Time to partial remission. ? Time to (and proportion achieving) early, sustained partial remission (partial remission which occurs on or before Week 24 which is sustained through Week 48). ? Time to sustained partial remission (defined as the first occurrence of partial remission which is sustained through Week 48). ? Change from baseline in UPCR at Weeks 24 and 48. ? Change from baseline in the Safety of Exogenous Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index score at Weeks 24 and 48. ? Change from baseline in serum creatinine, urine protein, serum albumin, eGFR at each visit measured. ? Proportion of subjects with active urinary sediment (defined by >10 red blood cells (RBC) per high powered field with dysmorphic RBC and/or RBC casts on urinalysis of a urine sample which has a minimum volume of 50 mL) at each visit measured. ? Change from baseline in immunology parameters (C3, C4, and anti-double-stranded DNA) and biomarkers at each visit measured;Timepoint(s) of evaluation of this end point: Timepoints as specified in section E.5.1.1 | — |
Countries
Argentina, Belarus, Bulgaria, Georgia, Guatemala, Mexico, Poland, Russian Federation, Serbia, Spain, Sri Lanka, Ukraine, United States
Contacts
Public ContactRegulatory Deparment
Pharm-Olam International (Spain) S.L.U.
Outcome results
None listed