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Lupus NephritisPhase 2NCT03610516

Safety, Pharmacokinetics and Preliminary Efficacy Study of CFZ533 in Patients With Lupus Nephritis.

A Phase 2 study testing CFZ533 in people with Lupus Nephritis, run by Novartis Pharmaceuticals at 21 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lupus Nephritis
What is being tested?
CFZ533
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
57 participants
Where
21 sitesin 10 countries
Study dates
12 Sep 2018to 29 Jun 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

21 sites in 10 countries.

21 sites in 10 countries

China5 sites
  • Novartis Investigative Site

    Beijing, 100730

  • Novartis Investigative Site

    Changsha, Hunan, 410008

  • Novartis Investigative Site

    Guangzhou, Guangdong, 510000

  • Novartis Investigative Site

    Shanghai, 200127

  • Novartis Investigative Site

    Ürümqi, Xinjiang, 830001

Other trials in China

Russia4 sites
  • Novartis Investigative Site

    Rostov-on-Don, 344022

  • Novartis Investigative Site

    Saint Petersburg, 197022

  • Novartis Investigative Site

    Saint Petersburg, 197110

  • Novartis Investigative Site

    Yaroslavl, 150062

Other trials in Russia

Taiwan3 sites
  • Novartis Investigative Site

    Taichung, 40447

  • Novartis Investigative Site

    Taichung, 40705

  • Novartis Investigative Site

    Taipei, 10048

Other trials in Taiwan

Argentina2 sites
  • Novartis Investigative Site

    Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO

  • Novartis Investigative Site

    Córdoba, X5016KEH

Other trials in Argentina

South Korea2 sites
  • Novartis Investigative Site

    Seoul, Seocho Gu, 06591

  • Novartis Investigative Site

    Seoul, 03080

Other trials in South Korea

Germany1 site
  • Novartis Investigative Site

    Mainz, 55131

Other trials in Germany

Hong Kong1 site
  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

Hungary1 site
  • Novartis Investigative Site

    Debrecen, 4032

Other trials in Hungary

Tunisia1 site
  • Novartis Investigative Site

    Tunis, 1008

Other trials in Tunisia

Turkey (Türkiye)1 site
  • Novartis Investigative Site

    Kocaeli, 41380

Other trials in Turkey (Türkiye)

About this study

Official title: 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

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.

Read the 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.

Conditions
Lupus Nephritis
Being tested
CFZ533, Placebo
Keywords
anti-CD40, CFZ533, moderately active lupus nephritis
Medical subject headings
Lupus Nephritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CFZ533Drug

    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.

  • PlaceboDrug

    multiple doses of placebo intravenous infusion

Study groups in NCT03610516
Study groupRoleWhat they receive
CFZ533ExperimentalInvestigational drug CFZ533 will be administred as multiple doses
Receives: Drug: CFZ533
PlaceboPlacebo comparatorInvestigational drug matching placebo will be administered as multiple doses
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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.

  2. 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.

    Measured: Baseline, Day 169

Secondary outcomes (10)
  1. 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.

    Measured: Day 197, Day 225, Day 253, Day 281, Day 309, Day 337 (End of Study)

  2. 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.

    Measured: Day 141: pre dose and 1 hour post dose

  3. 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.

    Measured: Pre-dose at: Day 1, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 141

  4. 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].

    Measured: Day 141: pre dose and 1 hour post dose

  5. 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.

    Measured: Day 1, Day 15, Day 29, Day 57, Day 113, Day 169, Day 225, Day 281, Day 337 (End of Study)

  6. Number of Participants With Anti-CFZ533 Antibodies

    To evaluate the immunogenicity of CFZ533 via the quasi-quantitative analysis of anti-CFZ533 antibodies.

    Measured: Day 1, Day 15, Day 29, Day 57, Day 113, Day 169, Day 225, Day 281, Day 337 (End of study)

  7. 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.

    Measured: Baseline, Day 1 (Pre dose), and Day 309

  8. 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.

    Measured: Day 1 (Pre dose), Day 15 (Pre dose), Day 29 (Pre dose), Day 253, and Day 337 (end of study)

  9. 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.

    Measured: 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)

  10. 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.

    Measured: Baseline, up to Day 169

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2018
  2. Study start12 Sep 2018
  3. Primary completion29 Jun 2023
  4. Study completion29 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03610516
Sponsor's protocol ID
CCFZ533X2202
Status last verified
Oct 2024
First submitted
1 Jun 2018
Last updated
9 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

Publications

  • Shen N, Weinmann-Menke J, Malvar A, Serra-Roma A, Weiss M, Danekula R, Sips C, Rohr J, Felten R, Gergely P, Shisha T. Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study. RMD Open. 2025 Aug 14;11(3):e005557. doi: 10.1136/rmdopen-2025-005557.

    PubMed 40813108

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CFZ533 in people with Lupus Nephritis, run by Novartis Pharmaceuticals at 21 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in China, Russia, Taiwan, Argentina, South Korea and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03610516, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2024.

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