- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03610516
Safety, Pharmacokinetics and Preliminary Efficacy Study of CFZ533 in Patients With Lupus Nephritis.
A Randomized, Placebo-controlled, Patient and Investigator Blinded, Study Investigating the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Multiple Doses of CFZ533 in Patients With Moderately Active Proliferative Lupus Nephritis
Study Overview
Detailed Description
This was a randomized, subject and investigator blind, placebo controlled multicenter study with multiple doses of CFZ533 administered by 1-hour intravenous infusion over a 24 week treatment period, as compared to matched placebo infusion. The treatment period was followed by a 24-week safety follow-up period.The duration of the study (including the screening period) for each patient was approximately 53 weeks. The investigational drug or placebo was administered on top of standard of care therapy for lupus nephritis.
Patients were screened within 29 days of the first study drug infusion. Eligibility was confirmed at the baseline visit within one week before the first dose. Eligible patients were assigned a randomization number and receive the intravenous infusion within 3 days of baseline visit.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Cordoba, Argentina, X5016KEH
- Novartis Investigative Site
-
-
Buenos Aires
-
Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1015ABO
- Novartis Investigative Site
-
-
-
-
-
Beijing, China, 100730
- Novartis Investigative Site
-
Shanghai, China, 200127
- Novartis Investigative Site
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510000
- Novartis Investigative Site
-
-
Hunan
-
Changsha, Hunan, China, 410008
- Novartis Investigative Site
-
-
Xinjiang
-
Urumqi, Xinjiang, China, 830001
- Novartis Investigative Site
-
-
-
-
-
Mainz, Germany, 55131
- Novartis Investigative Site
-
-
-
-
-
HongKong, Hong Kong
- Novartis Investigative Site
-
-
-
-
-
Debrecen, Hungary, 4032
- Novartis Investigative Site
-
-
-
-
-
Seoul, Korea, Republic of, 03080
- Novartis Investigative Site
-
-
Seocho Gu
-
Seoul, Seocho Gu, Korea, Republic of, 06591
- Novartis Investigative Site
-
-
-
-
-
Rostov on Don, Russian Federation, 344022
- Novartis Investigative Site
-
St-Petersburg, Russian Federation, 197022
- Novartis Investigative Site
-
St. Petersburg, Russian Federation, 197110
- Novartis Investigative Site
-
Yaroslavl, Russian Federation, 150062
- Novartis Investigative Site
-
-
-
-
-
Taichung, Taiwan, 40447
- Novartis Investigative Site
-
Taichung, Taiwan, 40705
- Novartis Investigative Site
-
Taipei, Taiwan, 10048
- Novartis Investigative Site
-
-
-
-
-
Tunis, Tunisia, 1008
- Novartis Investigative Site
-
-
-
-
-
Kocaeli, Turkey, 41380
- Novartis Investigative Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria:
- Men and women with systemic lupus erythematosus (SLE) 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 at al 1982, revised by Hochberg 1997)
- Subjects must have a body mass index (BMI) within the range of 18 - 40 kg/m2 at screening visit
- Histological diagnosis of proliferative lupus nephritis World Health Organization (WHO) ISN/RPS (Weening et al 2004) Class III or IV within 5 years of screening
- Presence of antinuclear autoantibody (ANA titer ≥ 1:80) at screening
- Morning UPCR ≥ 0.5 at screening visit and baseline visit
At least one of the following:
- low complement level (C3 ˂ 0.9 g/L) or (C4 ˂ 0.1 g/L), and/or
- elevated anti-dsDNA (≥ 30 IU/mL), and/or
- urine sediment consistent with active proliferative LN 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
- Patient must have sufficient kidney function as estimated by eGFR ˃ 30mL/min/1.73 m2 at screening and baseline visits (Levey et al 2009)
- Patient must have active disease as defined by proteinuria and additional symptoms as above despite standard of care therapy for LN 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 Bertsias et all 2012 and Hahn et al 2012.
- Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must use highly effective methods of contraception during dosing and until study completion.
Key Exclusion Criteria:
- 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.
- Hypoalbuminemia (serum albumin of less than 2.0 g/dL)
Patients who have received:
- oral or i.v. cyclophosphamide within 3 months prior to randomization
- i.v. corticosteroid bolus (dose ˃ 1 mg/kg) within 3 months prior to randomization
- rituximab or other B cell depleting agent within 12 months. for patients who received such treatment earlier, B cell count should be within normal ranges prior to randomization
- belimumab within 6 months prior to randomization
- any other biologic drug or an investigational drug within one months or five times the half-life, whichever is longer prior to randomization
- any calcineurin inhibitor (e.g., tacrolimus or cyclosporin A) within 3 months prior to randomization
Patients who are at significant risk for the thromboembolic events based on the following:
- history of either thrombosis or 3 or more spontaneous abortions
- presence of lupus anticoagulant or prolonged activated partial thromboplastin time (aPTT) and no prophylactic treatment with aspirin or anticoagulants as per local standard of care
- Have had signs or symptoms of a clinically significant systemic viral, bacterial or fungal infection within 30 days prior to randomization
- Live vaccines within 4 weeks of the first study drug infusion
Other protocol-defined inclusion/exclusion criteria may apply.
-
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CFZ533
Investigational drug CFZ533 will be administred as multiple doses
|
multiple doses of CFZ533 intravenous infusion
|
Placebo Comparator: Placebo
Investigational drug matching placebo will be administered as multiple doses
|
multiple doses of placebo intravenous infusion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety as assessed by adverse events
Time Frame: From baseline to week 49
|
Number and percentage of patients with adverse events
|
From baseline to week 49
|
Renal proteinuria
Time Frame: From baseline to week 25
|
Ratio from baseline in urinary protein creatinine ratio (UPCR) to week 25
|
From baseline to week 25
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Urine protein creatinine ratio (UPCR) and hematuria and cellular casts
Time Frame: From baseline to week 49
|
Ratio from baseline for urine protein creatinine ratio (UPCR) and hematuria and cellular casts to evaluate the renal effect.
|
From baseline to week 49
|
Plasma pharmacokinetics (PK) of CFZ533: the area under plasma concentration-time curve calculated to the last quantifiable concentration point (AUClast).
Time Frame: From baseline to week 49, pre dose and 1 hour post dose
|
The following PK parameter will be determined from the plasma concentration time profile of CFZ533: AUClast: AUClast is the area under plasma concentration-time curve calculated to the last quantifiable concentration point. |
From baseline to week 49, pre dose and 1 hour post dose
|
Complete renal remission
Time Frame: From baseline to week 49
|
Proportion of patients who fulfill the criteria for complete renal remission according to ACR recommendation
|
From baseline to week 49
|
Plasma pharmacokinetics (PK) of CFZ533: The observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval (Cthrough)
Time Frame: From baseline to week 49, pre dose and 1 hour post dose
|
Cthrough: The observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval
|
From baseline to week 49, pre dose and 1 hour post dose
|
Plasma pharmacokinetics (PK) of CFZ533: The observed maximum plasma concentration following drug administration at steady state (Cmax,ss)
Time Frame: From baseline to week 49, pre dose and 1 hour post dose
|
Cmax,ss: The observed maximum plasma (or serum or blood) concentration following drug administration at steady state [mass/volume]
|
From baseline to week 49, pre dose and 1 hour post dose
|
Plasma pharmacokinetics (PK) of CFZ533 The lowest plasma concentration observed during a dosing interval at steady state (Cmin,ss)
Time Frame: From baseline to week 49, pre dose and 1 hour post dose
|
Cmin,ss: The lowest plasma (or serum or blood) concentration observed during a dosing interval at steady state [mass/volume]
|
From baseline to week 49, pre dose and 1 hour post dose
|
Total soluble CD40 concentrations
Time Frame: From baseline to week 49
|
Total soluble CD40 concentrations in plasma
|
From baseline to week 49
|
Immunogenicity of CFZ533
Time Frame: From baseline to week 49
|
Incidence of ADA-positive patients
|
From baseline to week 49
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Kidney Diseases
- Urologic Diseases
- Connective Tissue Diseases
- Glomerulonephritis
- Lupus Erythematosus, Systemic
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Nephritis
- Lupus Nephritis
Other Study ID Numbers
- CCFZ533X2202
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lupus Nephritis
-
Imperial College LondonKarolinska Institutet; Ohio State University; Dutch Working Party on Systemic... and other collaboratorsTerminatedSystemic Lupus Erythematosus, Lupus NephritisUnited Kingdom
-
Sun Yat-sen UniversityCompleted
-
Peking UniversityCompleted
-
University Hospital, GrenobleInstitut de Biologie Structurale GrenobleCompletedSystemic Lupus Erythematosus NephritisFrance
-
Peking Union Medical College HospitalUnknownNephritis, LupusChina
-
Artiva Biotherapeutics, Inc.RecruitingLupus Nephritis - WHO Class IV | Lupus Nephritis - WHO Class IIIUnited States
-
Kyverna TherapeuticsRecruitingLupus Nephritis | Lupus Nephritis - WHO Class IV | Lupus Nephritis - WHO Class IIIGermany
-
Minia UniversityNot yet recruitingmfERG in Lupus NephritisEgypt
-
Kyverna TherapeuticsRecruitingLupus Nephritis | Lupus Nephritis - World Health Organization (WHO) Class III | Lupus Nephritis - WHO Class IVUnited States
-
Centre Hospitalier Universitaire, AmiensCompletedLupus Nephritis | Systemic Lupus Erythematosus (SLE)France
Clinical Trials on CFZ533
-
Novartis PharmaceuticalsCompletedPrimary Sjögren's SyndromeUnited States, Hungary, Germany, Switzerland, United Kingdom
-
Novartis PharmaceuticalsCompletedGraves' DiseaseGermany, United States
-
Novartis PharmaceuticalsActive, not recruitingType 1 Diabetes MellitusBelgium, Italy, Spain, United Kingdom, Germany, Slovenia
-
Novartis PharmaceuticalsCompletedSjögren SyndromeUnited States, United Kingdom, Netherlands, Australia, Austria, Israel, France, Germany, Greece, Hungary, Italy, Korea, Republic of, Japan, Portugal, Russian Federation, Turkey, Canada, Colombia, Romania, Argentina, Chile, Brazil, S...
-
Novartis PharmaceuticalsCompletedMyasthenia Gravis, GeneralizedTaiwan, Germany, Russian Federation, Denmark, Canada
-
Novartis PharmaceuticalsCompletedRheumatoid ArthritisUnited States, Taiwan
-
Novartis PharmaceuticalsActive, not recruitingSjogren's SyndromeUnited Kingdom, Netherlands, Australia, Austria, Israel, France, Germany, Greece, Hungary, Italy, United States, Korea, Republic of, Japan, Portugal, Russian Federation, Turkey, Canada, Colombia, Romania, Argentina, Chile, Brazil, S...
-
Novartis PharmaceuticalsActive, not recruitingSystemic Lupus Erythematosus (SLE)Hungary, Spain, Germany, Israel, Thailand, France, Russian Federation, China, Japan, Taiwan, Korea, Republic of, Poland, Australia, Argentina, Czechia
-
Novartis PharmaceuticalsRecruitingHidradenitis SuppurativaSpain, France, Austria, Germany, United States, Hungary, Belgium, Iceland, Netherlands, Denmark, Czechia
-
Novartis PharmaceuticalsCompletedKidney Transplant RejectionUnited States, Hungary, Japan, United Kingdom, Belgium, Spain, Netherlands, Germany, Australia, France, Korea, Republic of, Switzerland, Norway, Italy, Latvia, Sweden, Argentina, Brazil, Canada, Czechia