Safety, pharmacokinetics and preliminary efficacy study of CFZ533 in patients with lupus nephritis
- Conditions
- upus NephritisMedDRA version: 20.1Level: PTClassification code 10025140Term: Lupus nephritisSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2017-003230-93-HU
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
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 < 0.8 g/L or C4 < 1.6 g/L), and/or
b. elevated anti-dsDNA (=30 IU/mL), and/or
c. urine sediment consistent with active proliferative lupus nephritis such as presence of cellular (granular or red blood cell) casts or hematuria (>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
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 <100,000/mm3 (<100 x 109/L)
c) Hemoglobin (Hgb) <8.0 g/dL (<5mmol/L)
d) lymphocyte count <500/mm3 (<0.5 X 109/L)
e) neutrophil count <1500/mm3 (<1.5 X 109/L)
f) Clinical evidence of liver disease or liver injury or any of the following hepatic conditions:
- known history of alcohol abuse, chronic liver or biliary disease
- conjugated bilirubin greater than the ULN
- alkaline phosphatase (AP) greater than 3 x ULN
- AST (SGOT), ALT (SGPT) greater than 3 x ULN
- ?-glutamyl-transferase (GGT) greater than 3 x ULN
13. Live vaccines within 4 weeks of study drug infusion
14. Have donated blood or experienced a loss of blood >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method