A Phase 2 interventional study of CFZ533 and Placebo in Lupus Nephritis, sponsored by Novartis Pharmaceuticals. Completed at 21 sites in 10 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-10-09.
Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment
This study was to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary therapeutic efficacy of multiple doses of CFZ533 anti-CD40 monoclonal antibody in patients with moderately active lupus nephritis.
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.
245 studies on the registry are indexed under Nephritis; 56 are open to participants now.
This study's enrollment of 57 is above the median of 49 across 156 interventional studies indexed under Nephritis.
Browse Nephritis studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
At least one of the following:
Key Exclusion Criteria:
Patients who have received:
Patients who are at significant risk for the thromboembolic events based on the following:
Investigational drug CFZ533 will be administred as multiple doses
Drug: CFZ533
Investigational drug matching placebo will be administered as multiple doses
Drug: Placebo
Multiple doses of 10 mg/kg CFZ533 intravenous (IV) infusion. CFZ533 was administered every 4 weeks (Q4W; from Day 1 to Day 141), plus an additional dose of 10 mg/kg IV at Day 15, resulting in a Q2W loading regimen up to the third dose on Day 29.
multiple doses of placebo intravenous infusion
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation.
Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 49 weeks.
Ratio to Baseline in Urinary Protein Creatinine Ratio (UPCR)
A urine protein creatinine ratio (UPCR) test is a urine test. It measures the levels of protein and creatinine in urine. UPCR was assessed using the first morning void if available at a visit otherwise using the clinic spot sample, and was expressed as protein/creatinine (mg/mmol). High UPCR values can be a sign of kidney disease. An UPCR ratio to baseline \<1 indicates improvement from baseline.
Time frame: Baseline, Day 169
Ratio to Baseline for Urine Protein Creatinine Ratio (UPCR)
A urine protein creatinine ratio (UPCR) test is a urine test. It measures the levels of protein and creatinine in urine. UPCR was assessed using the first morning void if available at a visit otherwise using the clinic spot sample, and was expressed as protein/creatinine (mg/mmol). High UPCR values can be a sign of kidney disease. An UPCR ratio to baseline \<1 indicates improvement from baseline.
Time frame: Day 197, Day 225, Day 253, Day 281, Day 309, Day 337 (End of Study)
Area Under Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of CFZ533
Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis. AUClast is the area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (tlast) of free CFZ533.
Time frame: Day 141: pre dose and 1 hour post dose
Pre-dose Trough Concentration (Ctrough) of CFZ533
Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis. Ctrough is the observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval.
Time frame: Pre-dose at: Day 1, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 141
The Observed Maximum Plasma Concentration Following CFZ533 Administration at Steady State (Cmax,ss)
Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis. Cmax,ss is the observed maximum plasma concentration following CFZ533 administration at steady state \[mass/volume\].
Time frame: Day 141: pre dose and 1 hour post dose
Total Soluble CD40 Plasma Concentrations
Total soluble CD40 concentrations in plasma. An increase in soluble CD40 concentrations is considered a marker for CFZ533 target engagement. This endpoint is only applicable to the CFZ533 arm.
Time frame: Day 1, Day 15, Day 29, Day 57, Day 113, Day 169, Day 225, Day 281, Day 337 (End of Study)
Number of Participants With Anti-CFZ533 Antibodies
To evaluate the immunogenicity of CFZ533 via the quasi-quantitative analysis of anti-CFZ533 antibodies.
Time frame: Day 1, Day 15, Day 29, Day 57, Day 113, Day 169, Day 225, Day 281, Day 337 (End of study)
Hematuria Casts- Urine White Blood Cell Casts
Urine was tested using a dipstick. If the dipstick result was positive for protein, nitrite, leucocytes and/or blood, a microscopic analysis of white blood cells (WBC), red blood cells (RBC) and casts was performed. Hematuria is the presence of blood in the urine. Hematuria casts were assessed by microscopic urinalysis and classified as granular casts and WBC casts. Only in the event of a positive result, these samples were submitted to reflex testing microscopic analysis for counting of casts which resulted in a numeric value related to the number of respective casts presented in the urine.
Time frame: Baseline, Day 1 (Pre dose), and Day 309
Hematuria Casts- Casts Granular
Urine was tested using a dipstick. If the dipstick result was positive for protein, nitrite, leucocytes and/or blood, a microscopic analysis of white blood cells (WBC), red blood cells (RBC) and casts was performed. Hematuria is the presence of blood in the urine. Hematuria casts were assessed by microscopic urinalysis and classified as granular casts and WBC casts. Only in the event of a positive result, these samples were submitted to reflex testing microscopic analysis for counting of casts which resulted in a numeric value related to the number of respective casts presented in the urine.
Time frame: Day 1 (Pre dose), Day 15 (Pre dose), Day 29 (Pre dose), Day 253, and Day 337 (end of study)
Change From Baseline in Urine Hyaline Casts
Urine was tested using a dipstick. If the dipstick result was positive for protein, nitrite, leucocytes and/or blood, a microscopic analysis of white blood cells (WBC), red blood cells (RBC) and casts was performed. Urine hyaline casts were assessed by microscopic urinalysis.
Time frame: Baseline, Day 1 (Pre dose), Day 15 (Pre dose), Day 29 (Pre dose), Day 57 (Pre dose), Day 85 (Pre dose), Day 113 (Pre dose), Day 141 (Pre dose), Day 169, Day 197, Day 225, Day 253, Day 281, Day 309 and Day 337 (end of study)
Number of Participants Who Fulfil the Criteria for Complete Renal Remission (CRR)
The criteria for CRR were defined as: 1. Urinary protein creatinine ratio (UPCR) ≤ 0.2 mg/mg 2. Estimated glomerular filtration rate (eGFR) ≤ 25% of Baseline 3. Normal urine sediment. If the UPCR from the first morning void sample was not available, then the UPCR from the corresponding spot sample taken at the investigator site was used in the derivation of complete renal remission.
Time frame: Baseline, up to Day 169
Participants took part in 21 investigative sites in 10 countries.
| Milestone | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Started | 39 | 18 |
| Completed | 21 | 10 |
| Not completed | 18 | 8 |
| Withdrew: Adverse event | 3 | 1 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Lack of efficacy | 0 | 1 |
| Withdrew: No longer requires treatment | 1 | 0 |
| Withdrew: Non-compliance with study treatment | 1 | 0 |
| Withdrew: Physician decision | 8 | 5 |
| Withdrew: Protocol deviation | 1 | 0 |
| Withdrew: Withdrawal by subject | 3 | 1 |
| Milestone | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Started | 34 | 16 |
| Completed | 32 | 16 |
| Not completed | 2 | 0 |
| Withdrew: Subject/guardian decision | 1 | 0 |
| Withdrew: Death | 1 | 0 |
Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation.
| Participants | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Adverse Events | 33 | 18 |
| Serious Adverse Events | 6 | 3 |
| AEs leading to discontinuation of study treatment | 3 | 1 |
| SAEs leading to discontinuation of study treatment | 0 | 0 |
A urine protein creatinine ratio (UPCR) test is a urine test. It measures the levels of protein and creatinine in urine. UPCR was assessed using the first morning void if available at a visit otherwise using the clinic spot sample, and was expressed as protein/creatinine (mg/mmol). High UPCR values can be a sign of kidney disease. An UPCR ratio to baseline \<1 indicates improvement from baseline.
| ratio to baseline in UPCR | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Ratio to Baseline in Urinary Protein Creatinine Ratio (UPCR) | 0.369 (0.234 to 0.582) | 0.637 (0.338 to 1.202) |
A urine protein creatinine ratio (UPCR) test is a urine test. It measures the levels of protein and creatinine in urine. UPCR was assessed using the first morning void if available at a visit otherwise using the clinic spot sample, and was expressed as protein/creatinine (mg/mmol). High UPCR values can be a sign of kidney disease. An UPCR ratio to baseline \<1 indicates improvement from baseline.
| ratio to baseline in UPCR | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Day 197 | 0.532 ± 0.4160 | 0.985 ± 0.9045 |
| Day 225 | 0.456 ± 0.3876 | 1.153 ± 1.2178 |
| Day 253 | 0.648 ± 1.3314 | 0.667 ± 0.3612 |
| Day 281 | 0.526 ± 0.5440 | 0.701 ± 0.7690 |
| Day 309 | 0.580 ± 0.7175 | 1.101 ± 1.1337 |
| Day 337 | 0.640 ± 0.7446 | 0.735 ± 0.5323 |
Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis. AUClast is the area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (tlast) of free CFZ533.
| day*ug/mL | CFZ533 10 mg/kg i.v. |
|---|---|
| Area Under Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of CFZ533 | 7250 ± 1800 |
Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis. Ctrough is the observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval.
| ug/mL | CFZ533 10 mg/kg i.v. |
|---|---|
| Day 1 | 0 ± 0 |
| Day 15 | 49.8 ± 37.0 |
| Day 29 | 64.1 ± 31.6 |
| Day 57 | 34.5 ± 21.7 |
| Day 85 | 33.2 ± 25.0 |
| Day 113 | 32.7 ± 26.3 |
| Day 141 | 34.1 ± 26.6 |
Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis. Cmax,ss is the observed maximum plasma concentration following CFZ533 administration at steady state \[mass/volume\].
| ug/mL | CFZ533 10 mg/kg i.v. |
|---|---|
| The Observed Maximum Plasma Concentration Following CFZ533 Administration at Steady State (Cmax,ss) | 263 ± 81.8 |
Total soluble CD40 concentrations in plasma. An increase in soluble CD40 concentrations is considered a marker for CFZ533 target engagement. This endpoint is only applicable to the CFZ533 arm.
| ng/mL | CFZ533 10 mg/kg i.v. |
|---|---|
| Day 1 | 0.2723 ± 0.22222 |
| Day 15 | 78.7375 ± 20.58802 |
| Day 29 | 90.4286 ± 23.86165 |
| Day 57 | 127.6214 ± 26.11617 |
| Day 113 | 109.2672 ± 50.19834 |
| Day 169 | 158.5714 ± 22.24753 |
| Day 225 | 8.3406 ± 17.77703 |
| Day 281 | 0.7981 ± 0.32464 |
| Day 337 (End of Study) | 0.5331 ± 0.30080 |
To evaluate the immunogenicity of CFZ533 via the quasi-quantitative analysis of anti-CFZ533 antibodies.
| Participants | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Day 1-Negative | 32 | 13 |
| Day 1-Positive | 1 | 0 |
| Day 15-Negative | 17 | 8 |
| Day 15-Positive | 0 | 0 |
| Day 29-Negative | 33 | 16 |
| Day 29-Positive | 0 | 0 |
| Day 57-Negative | 17 | 8 |
| Day 57-Positive | 0 | 0 |
| Day 113-Negative | 32 | 15 |
| Day 113-Positive | 0 | 0 |
| Day 169-Negative | 14 | 8 |
| Day 169-Positive | 0 | 0 |
| Day 225-Negative | 25 | 13 |
| Day 225-Positive | 1 | 0 |
| Day 281-Negative | 23 | 13 |
| Day 281-Positive | 1 | 0 |
| Day 337-Negative (EOS) | 12 | 8 |
| Day 337-Positive (EOS) | 1 | 0 |
Urine was tested using a dipstick. If the dipstick result was positive for protein, nitrite, leucocytes and/or blood, a microscopic analysis of white blood cells (WBC), red blood cells (RBC) and casts was performed. Hematuria is the presence of blood in the urine. Hematuria casts were assessed by microscopic urinalysis and classified as granular casts and WBC casts. Only in the event of a positive result, these samples were submitted to reflex testing microscopic analysis for counting of casts which resulted in a numeric value related to the number of respective casts presented in the urine.
| number of casts per low power field | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Baseline | 2 | — |
| Day 1 | 2 | — |
| Day 309 | 4 | — |
Urine was tested using a dipstick. If the dipstick result was positive for protein, nitrite, leucocytes and/or blood, a microscopic analysis of white blood cells (WBC), red blood cells (RBC) and casts was performed. Hematuria is the presence of blood in the urine. Hematuria casts were assessed by microscopic urinalysis and classified as granular casts and WBC casts. Only in the event of a positive result, these samples were submitted to reflex testing microscopic analysis for counting of casts which resulted in a numeric value related to the number of respective casts presented in the urine.
| number of casts per low power field | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Day 1 | 3 | — |
| Day 15 | 2.5 ± 0.71 | — |
| Day 29 | — | 3 ± 1.41 |
| Day 253 | 14.0 | — |
| Day 337 (End of Study) | 5 ± 2.83 | — |
Urine was tested using a dipstick. If the dipstick result was positive for protein, nitrite, leucocytes and/or blood, a microscopic analysis of white blood cells (WBC), red blood cells (RBC) and casts was performed. Urine hyaline casts were assessed by microscopic urinalysis.
| number of casts per low power field | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Day 15 | 8.3 ± 15.88 | 3.7 ± 3.51 |
| Day 29 | 2.8 ± 4.99 | 5.0 ± 2.16 |
| Day 57 | -5.0 ± 3.61 | 1.0 ± 1.41 |
| Day 85 | 0.5 ± 2.12 | -4.0 |
| Day 113 | — | 18.0 ± 28.58 |
| Day 141 | — | -4.5 ± 6.36 |
| Day 169 | 0.0 | 0.0 |
| Day 197 | -1.0 ± 2.65 | 2.7 ± 9.02 |
| Day 225 | 2.0 | 0.0 |
| Day 253 | — | -0.5 ± 4.95 |
| Day 281 | 0.0 | -1.5 ± 4.95 |
| Day 309 | 1.7 ± 1.15 | -4.0 |
| Day 337 (EOS) | — | 0.5 ± 0.71 |
The criteria for CRR were defined as: 1. Urinary protein creatinine ratio (UPCR) ≤ 0.2 mg/mg 2. Estimated glomerular filtration rate (eGFR) ≤ 25% of Baseline 3. Normal urine sediment. If the UPCR from the first morning void sample was not available, then the UPCR from the corresponding spot sample taken at the investigator site was used in the derivation of complete renal remission.
| Participants | CFZ533 10 mg/kg i.v. | Placebo i.v. |
|---|---|---|
| Number of Participants Who Fulfil the Criteria for Complete Renal Remission (CRR) | 13 | 4 |
Collected over Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 49 weeks.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| CCFZ533 10mg/kg | 2/39 (5.1%) | 6/39 (15.4%) | 32/39 (82.1%) |
| Placebo i.v. | 0/18 (0%) | 3/18 (16.7%) | 18/18 (100%) |
| All Patients | 2/57 (3.5%) | 9/57 (15.8%) | 50/57 (87.7%) |
| Event | CCFZ533 10mg/kg | Placebo i.v. | All Patients |
|---|---|---|---|
| CholecystitisHepatobiliary disorders | 0/39 | 1/18 | 1/57 |
| Systemic lupus erythematosusMusculoskeletal and connective tissue disorders | 0/39 | 1/18 | 1/57 |
| Suicidal behaviourPsychiatric disorders | 0/39 | 1/18 | 1/57 |
| Lupus nephritisRenal and urinary disorders | 0/39 | 1/18 | 1/57 |
| Haemophagocytic lymphohistiocytosisImmune system disorders | 1/39 | 0/18 | 1/57 |
| BronchitisInfections and infestations | 1/39 | 0/18 | 1/57 |
| Cytomegalovirus infection reactivationInfections and infestations | 1/39 | 0/18 | 1/57 |
| GastroenteritisInfections and infestations | 1/39 | 0/18 | 1/57 |
| PneumoniaInfections and infestations | 1/39 | 0/18 | 1/57 |
| Urinary tract infectionInfections and infestations | 1/39 | 0/18 | 1/57 |
| Event | CCFZ533 10mg/kg | Placebo i.v. | All Patients |
|---|---|---|---|
| Upper respiratory tract infectionInfections and infestations | 7/39 | 2/18 | 9/57 |
| COVID-19Infections and infestations | 5/39 | 3/18 | 8/57 |
| Urinary tract infectionInfections and infestations | 2/39 | 3/18 | 5/57 |
| Oedema peripheralGeneral disorders | 1/39 | 2/18 | 3/57 |
| Herpes simplexInfections and infestations | 0/39 | 2/18 | 2/57 |
| HeadacheNervous system disorders | 1/39 | 2/18 | 3/57 |
| NasopharyngitisInfections and infestations | 4/39 | 0/18 | 4/57 |
| LeukocytosisBlood and lymphatic system disorders | 3/39 | 0/18 | 3/57 |
| Herpes zosterInfections and infestations | 3/39 | 1/18 | 4/57 |
| Neutrophil count increasedInvestigations | 3/39 | 0/18 | 3/57 |
| Age, Continuous(years) | CFZ533 10 mg/kg i.v. | Placebo i.v. | Total |
|---|---|---|---|
| Mean | 34.1 ± 9.20 | 36.4 ± 9.15 | 34.8 ± 9.17 |
| Sex: Female, Male(Participants) | CFZ533 10 mg/kg i.v. | Placebo i.v. | Total |
|---|---|---|---|
| Female | 30 | 17 | 47 |
| Male | 9 | 1 | 10 |
| Race/Ethnicity, Customized(Participants) | CFZ533 10 mg/kg i.v. | Placebo i.v. | Total |
|---|---|---|---|
| White | 16 | 7 | 23 |
| Asian | 23 | 11 | 34 |
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Plan to share: Yes — 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.
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