Lupus Nephritis MedDRA version: 20.1 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Code: CFZ533
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: Not yet available
Other descriptive name: CFZ533
Concentration unit: mg/ml milligram(s)/m
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Population eligible for inclusion in this study must fulfill all of the following criteria: 1. Understand the study procedures and provide written informed consent before any study-related assessment is performed. 2. Men and women with systemic lupus erythematosus (see below), aged =18 years and =75 years at screening, fulfilling at least 4 out of 11 criteria for SLE as defined by the American College of Rheumatology (Tan et al 1982, revised by Hochberg 1997). 3. Subjects must have a body mass index (BMI) within the range of 18 - 40 kg/m2. (BMI = Body weight (kg) / [Height (m)]2) to participate in the study 4. Histological diagnosis of proliferative lupus nephritis World Health Organization (WHO) ISN/RPS (Weening et al 2004) Class III or IV within 2 years of screening 5. Presence of antinuclear autoantibody (ANA titer =1:80 at screening) 6. First morning UPCR =0.5 at Screening visit and Baseline visit (at least five days apart) 7. At least one of the following at Screening visit: a. low complement level (C3 5 red blood cells per high power field) if other causes such as menstrual bleeding are excluded 8. Patient must have sufficient kidney function as estimated by eGFR >30 mL/min/1.73m2 9. Patients must have active disease as defined by proteinuria and additional symptoms as defined above (criterion 7) despite standard of care therapy for lupus nephritis as considered appropriate by the treating physician (e.g., corticosteroids and/or immunosuppressive or immunomodulatory treatments such as mycophenolate, azathioprine, methotrexate or hydroxychloroquine). For guidance, see published guidelines such as by Bertsias et al 2012 and Hahn et al 2012 10. If the patient is taking oral corticosteroid treatment at screening, the dose (max. 30 mg prednisone or equivalent per day) must be stable for at least 2 weeks prior to randomization 11. If the patient is taking immunosuppressive or immunomodulatory treatment such as mycophenolate, azathioprine, methotrexate or hydroxychloroquine, the dose must be stable for at least 4 weeks prior to randomization and for the duration of the study 12. If the patient is taking a medication potentially affecting renal function (such as ACE inhibitors, cholesterol-lowering agents) the dose must be stable for at least 4 weeks prior to randomization and for the duration of the study 13. Vaccinations, if deemed necessary, must be up to date based on local guidelines 14. Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) must use highly effective methods of contraception before entering the study, during dosing and until study completion. Other protocol defined inclusion criteria may apply. 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 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Eligible Population fulfilling any of the following criteria are not eligible for inclusion in this study: 1. Any glomerulonephritis other than WHO Class III or IV lupus nephritis. Patients with proliferative nephritis (Class III or IV) who, in addition, have overlapping histological signs for other glomerulonephritis, e.g. Class V are eligible at the investigator`s discretion 2. Hypoalbuminemia (serum albumin of less than 2.0 g/dL) 3. Patients who have received a) oral or IV cyclophosphamide within 3 months b) IV corticosteroid bolus (dose higher than 1 mg/kg) within 3 months c) rituximab or other B cell depleting agent within 12 months. For patients who received such treatment earlier, B cell count should be within normal range d) belimumab within 6 months e) any other biologic drug or an investigational drug within one (1) month or five times the half-life, whichever is longer f) calcineurin inhibitor (e.g., tacrolimus, cyclosporin A) within 3 months 4. Patients who are at significant risk for thromboembolic events based on the following: - History of either thrombosis or 3 or more spontaneous abortions - Presence of lupus anticoagulant or prolonged partial thromboplastin time (PTT) and no prophylactic treatment with aspirin or anticoagulants as per local standard of care 5. History or presence of any medically significant cardiac condition which according to the investigator may jeopardize the patient in case of participation in the study including ischemic heart disease, congestive heart failure or cardiomyopathy, myocardial infarction or stroke 6. History of malignancy with the exception of basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix within the last 3 years 7. Have had signs or symptoms of a clinically significant systemic viral, bacterial or fungal infection within 30 days prior to randomization 8. Evidence of active or latent tuberculosis as assessed by Quantiferon testing at screening (PPD is not recommended as immunosuppression may result in false negative result) 9. Positive serology for HIV antibodies, hepatitis B surface antigen, or hepatitis C antibodies confirmed by an appropriate licensed test at screening 10. Any other current, active or latent infection susceptible to reactivation 11. Any significant concurrent medical condition such as pulmonary or liver disease that, in the opinion of the principal Investigator, could affect the patient's ability to tolerate or complete the study 12. Any of the following abnormal laboratory values: a) total white blood cell count (WBC) outside the range of 1,500-15,000/mm3 (1.5-15.0 x 109/L) b) platelets 500mL within 4 weeks of screening 15. Known allergy to human antibodies No additional exclusions may be applied by the investigator, in order to ensure that the study population will be represe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of 24 weeks of treatment with CFZ533 as an add-on therapy to standard of care in moderately active lupus nephritis (LN) patients; To assess the effect of CFZ533 on renal proteinuria in moderately active lupus nephritis patients after 24 weeks of treatment as an add-on therapy to standard of care as compared to placebo;Secondary Objective: To assess the effect of CFZ533 on relevant renal outcomes at different time points; To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of CFZ533 in LN patients, after multiple 10 mg/kg IV doses; To evaluate the immunogenicity of CFZ533 in LN patients, after multiple 10 mg/kg IV doses;Primary end point(s): 1. Safety: - AEs/SAEs - Vital signs - ECG evaluation - Standard hematology and chemistry evaluations 2. Ratio from baseline in urinary protein creatinine ratio (UPCR) at Week 25;Timepoint(s) of evaluation of this end point: 1. All visits from baseline to Week 49 2. UPCR: visits Day 1 and Day 169 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Ratio from baseline in the following parameters: -- UPCR -- hematuria and cellular casts - Proportion of patients who fulfill the criteria for complete renal remission (CRR) according to ACR recommendation (Wofsy et al 2012) - PK: Free CFZ533 concentrations in plasma. - Parameters (free CFZ533): Ctrough,ss or Cmin,ss, Cmax,ss, and AUClast (after last dose) - PD: Total soluble CD40 concentrations in plasma: pre-dose, during treatment and follow up. Rate, extent and duration of target engagement. - Anti-CFZ533 antibodies in plasma: baseline, during treatment and followup, incidence of ADA-positive patients;Timepoint(s) of evaluation of this end point: Baseline visit, and all visits from Day 1 to Day 337. | — |
Countries
Argentina, China, Germany, Hong Kong, Hungary, Korea, Republic of, Russian Federation, Taiwan, Tunisia, Turkey, United States
Contacts
Public ContactPublic Information Desk
Novartis Hungary Kft.
Outcome results
None listed