Clinical study comparing the efficacy in the achievement of the remission (measured as reduction of proteinuria) and safety of two different doses of voclosporin and non active drug (placebo) in patients suffering from active lupus nephritis
- Conditions
- Active lupus nephritisMedDRA version: 18.0Level: PTClassification code 10025140Term: Lupus nephritisSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2012-003364-51-PL
- Lead Sponsor
- Aurinia Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 258
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 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;
see Appendix 5. If a subject has not had a recent kidney biopsy, one may be
performed to assess eligibility into the study provided consent is in place and
provided results are received before randomization.
5. Subjects with laboratory evidence of active nephritis at screening, defined as
follows:
• Class III, IV-S or IV-G
Confirmed proteinuria =1,500 mg/24 hours when assessed by 24-hour urine
collection, defined by a urine protein/creatinine ratio (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 228
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
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.
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/µL; 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>compared to placebo in subjects with active LN.<br><br>• To assess the efficacy of 2 doses of voclosporin versus placebo over 48 weeks in<br>subjects with active LN.;Primary end point(s): Primary Endpoint:<br>Complete remission is defined as:<br>• Confirmed protein/creatinine ratio of =0.5 mg/mg and<br>• eGFR =60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of<br>=20%.<br>Subjects who receive rescue medication for lupus (see Section 7.8, Prohibited<br>Therapy and Concomitant Treatment) or >10 mg prednisone for >3 consecutive<br>days or >7 days total from Weeks 16-26 will not be considered as achieving<br>complete remission.;Timepoint(s) of evaluation of this end point: Week 24
- Secondary Outcome Measures
Name Time Method