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

NCT03610516 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CCFZ533X2202
• Study Type: interventional
• Target: 57
• Locations: 9 countries
• Sites: 20

Brief 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.

Conditions

Lupus Nephritis

Keywords

anti-CD40; CFZ533; moderately active lupus nephritis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline, Day 169

Secondary Outcomes (10)

• Ratio to Baseline for Urine Protein Creatinine Ratio (UPCR)

  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

  Day 141: pre dose and 1 hour post dose

• Pre-dose Trough Concentration (Ctrough) of CFZ533

  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)

  Day 141: pre dose and 1 hour post dose

• Total Soluble CD40 Plasma Concentrations

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

Study Arms (2)

CFZ533

EXPERIMENTAL

Investigational drug CFZ533 will be administred as multiple doses

Drug: CFZ533

Placebo

PLACEBO COMPARATOR

Investigational drug matching placebo will be administered as multiple doses

Drug: Placebo

Interventions

CFZ533 DRUG

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.

CFZ533

Placebo DRUG

multiple doses of placebo intravenous infusion

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO, Argentina

Location

Novartis Investigative Site

Córdoba, X5016KEH, Argentina

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

Location

Novartis Investigative Site

Changsha, Hunan, 410008, China

Location

Novartis Investigative Site

Ürümqi, Xinjiang, 830001, China

Location

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Shanghai, 200127, China

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Rostov-on-Don, 344022, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197110, Russia

Location

Novartis Investigative Site

Yaroslavl, 150062, Russia

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Taichung, 40447, Taiwan

Location

Novartis Investigative Site

Taichung, 40705, Taiwan

Location

Novartis Investigative Site

Taipei, 10048, Taiwan

Location

Novartis Investigative Site

Tunis, 1008, Tunisia

Location

Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 40813108 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Lupus Nephritis

Interventions

iscalimab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2018
• First Posted: August 1, 2018
• Study Start: September 12, 2018
• Primary Completion: June 29, 2023
• Study Completion: June 29, 2023
• Last Updated: October 9, 2024
• Results First Posted: July 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

RU (4); TU (1); KR (2); HK (1); CN (5); AR (2); HU (1); DE (1); TW (3)