Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis

Purpose

This trial will evaluate efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN

Condition

  • Lupus Nephritis

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

Participants eligible for inclusion in this study must meet all of the following criteria: - Adult male and female participants aged 18 years or older at the time of screening - Weigh at least 35 kg at screening - Have a confirmed clinical diagnosis of SLE according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Systemic Lupus Erythematosus (SLE) classification criteria - Have a positive anti-nuclear antibody (ANA) test result; ANA titer ≥ 1:80 at screening visit based on central or local laboratory result - Active LN at screening, as defined by meeting the 3 following criteria: - Renal biopsy within 6 months prior to screening period indicating ISN/RPS class III or IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous LN. If no biopsy was performed within 6 months prior to screening period, a biopsy will need to be performed during the screening period after having met all other inclusion/

Exclusion Criteria

. - UPCR ≥ 1.0 g/g on 24h urine collection at Screening - eGFR ≥ 25mL/min/1.73 m2. Participants with eGFR < 30 mL/min/1.73 m2 require renal biopsy during the screening period showing sclerosis in ≤ 50% of glomeruli - Newly diagnosed participants as well as pre-treated LN participants (including refractory cases) can be included, as long as they are currently on, or willing to initiate SoC induction therapy for LN using MPA - Induction therapy, as defined by treatment including both high dose corticosteroids and MPA, should be initiated prior to or on day of randomization - Anti-malarial treatment at stable dosing prior to randomization is strongly recommended, in the absence of contraindications - Participants on azathioprine treatment at Screening must be switched to MPA prior to randomization - Receipt of at least one dose of pulse methylprednisolone i.v. (250 - 1000 mg per day up to 3000 mg cumulative dose) or equivalent for treatment of current episode of active LN within 60 days prior randomization. Participant who cannot take the pulse i.v. corticosteroid therapy should directly start on 0.8-1.0 mg/day (max 80mg/day) oral predniso(lo)ne. - Able to communicate well with the Investigator to understand and comply with the requirements of the study Exclusion Criteria: Participants meeting any of the following criteria are not eligible for inclusion in this study: - Severe renal impairment as defined by i.) presence of oliguria (defined as a documented urine volume <400 mL/24 hrs) or ii.) End-Stage Renal Disease (ESRD) requiring dialysis or transplantation - Sclerosis in > 50% of glomeruli on renal biopsy - Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline. Use of certain Traditional Chinese Medicines - Prior use of ianalumab (ever); or prior use other B cell depleting therapy within 36 weeks prior to randomization or if therapy was administered < 36 weeks prior to randomization, B cell count less than the lower limit of normal or patient's own baseline value prior to having received an earlier B cell-depleting therapy - Prior treatment with any of the following within 12 weeks prior to randomization - Belimumab, telitacicept, abatacept, TNF-α mAb, immunoglobulins (i.v./s.c.) plasmapheresis - Any other immuno-suppressants (i.v. or oral cyclophosphamide, calcineurin inhibitors, JAK inhibitors or other kinase inhibitors) - Thalidomide treatment and/or methotrexate - Combination of DMARDs - Imidazole derivative (e.g., azathioprine, mizoribine) must be discontinued prior to starting treatment with MPA - Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within 12 weeks prior to randomization - History of major organ transplant or hematopoietic stem cell/bone marrow transplant or are due to receive transplantation - Any one of the following laboratory values at screening: - Hemoglobin levels < 8.0 g/dL (< 5 mmol/L), or < 7.0 g/dL (< 4.3 mmol/L) if related to participant's SLE such as in active hemolytic anaemia - Platelet count < 25 x 1000/µL - Absolute neutrophil count (ANC) < 0.8 x 1000/µL - Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection or history of recurrent clinically significant infection which in the opinion of the investigator will place the participant at risk for participation. - History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component of the study drug(s) or its excipients - Receipt of live/attenuated vaccine within a 4-week period prior to randomization - History of primary or secondary immunodeficiency, including a positive HIV test result - History of malignancy of any organ system (other than localized basal cell carcinoma or squamous cell carcinoma of the skin or or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases - Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes), psychiatric or additional physical condition that the Investigator feels may jeopardize the participants in case of participation in this study - Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis B surface antigen (HBsAg) excludes the participant - Evidence of active tuberculosis (TB) infection (after anti-TB treatment, participants with history of TB may become eligible according to national local guidelines) - Pregnant or nursing (lactating) women - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 6 months after stopping of investigational medication - Sexually active male participants, who do not agree to use barrier protection during intercourse with women of child-bearing potential while taking study treatment Other protocol -defined Inclusion/Exclusion may apply.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This is a pivotal double-blind, randomized, placebo-controlled, multi-center three-arm study, evaluating at Week 72 efficacy and safety of ianalumab administered s.c. every 4 weeks or ianalumab administered s.c. every 12 weeks versus placebo, administered s.c. every 4 weeks, in adult participants with active LN receiving SoC. In addition, long-term efficacy, safety and tolerability will be collected up to Week 144.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double-blind

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm 1 - ianalumab s.c. q4w
ianalumab s.c. q4w in addition to standard of care (SoC)
  • Drug: ianalumab s.c. q4w
    ianalumab s.c. q4w in addition to SoC
    Other names:
    • VAY736
Experimental
Arm 2 - ianalumab s.c. q12w
ianalumab s.c. q12w in addition to SoC
  • Drug: ianalumab s.c. q12w
    ianalumab s.c. q12w in addition to SoC
    Other names:
    • VAY736
Placebo Comparator
Arm 3 - placebo s.c. q4w
Placebo s.c. q4w in addition to SoC
  • Drug: placebo s.c.
    placebo s.c. q4w in addition to SoC
    Other names:
    • placebo

Recruiting Locations

University Of Alabama
Birmingham, Alabama 35294
Contact:
Alason Koenig
alasonkoenig@uabmc.edu

Advanced Medical Research
La Palma, California 90623
Contact:
Reza Azadegan
562-867-8195
razadegan@advmedresearch.com

University of California LA
Los Angeles, California 90095
Contact:
Aima Ohiwerei
310-825-9447
AOhiwerei@mednet.ucla.edu

University of California Irvine
Orange, California 92868
Contact:
Ahmad Walid Roshan
ahmadwar@hs.uci.edu

School Of Medicine
Sacramento, California 95817
Contact:
Chenoa Vargas
crcvargas@ucdavis.edu

University of California San Diego
San Diego, California 92037
Contact:
Bosco Trinh
+1 858 534 2555
botrinh@health.ucsd.edu

Kaiser Permanente
San Diego, California 92111
Contact:
Michael D Fechter
858-401-7205
MICHAEL.D.FECHTER@KP.ORG

Mayo Clinic Jacksonville
Jacksonville, Florida 32224
Contact:
Tia Wilkes
904-953-2451
Wilkes.Quantia@mayo.edu

University Of Miami
Miami, Florida 33136
Contact:
Niurka Colina
305-243-2568
nxc610@miami.edu

Emory University School of Medicine
Atlanta, Georgia 30303
Contact:
Karla Caylor
404-616-4440
kcaylor@emory.edu

Fides Clinical Research
Atlanta, Georgia 30342
Contact:
Victoria Givans
404-252-0256
vgivans@fidesclinicalresearch.com

Parris and Associates Rheumatology
Lawrenceville, Georgia 30044
Contact:
Mannai Coutermarsh
+17709621616#8334
m.coutermarsh@parrisandassociates.net

Accurate Clinical Research
Lake Charles, Louisiana 70601

UMC New Orleans
New Orleans, Louisiana 70112
Contact:
Cathryn Leggio
cathryn.leggio@LCMChealth.org

Wayne State University
Detroit, Michigan 48201
Contact:
Biljana Basic-Panic
313-745-7371
bbasicpanic@med.wayne.edu

Univ of Nevada School of Med
Las Vegas, Nevada 89102
Contact:
Priscilla Herrera
priscilla.herrera@unlv.edu

VA NM Healthcare System
Albuquerque, New Mexico 87108
Contact:
Maria Munoz
505-265-1711
Maria.Munoz3@va.gov

NY Nephrology
Clifton Park, New York 12065
Contact:
Tatiana Cordero
518-579-0017
tatiana.cordero@nyneph.com

Hospital for Special Surgery
New York, New York 10021
Contact:
Natasha Zarrin
212-606-1728
zarrinn@hss.edu

Northwell Health
New York, New York 10028
Contact:
Radha Puran
516-708-2550
rpuran@northwell.edu

Circuit Clinical
Orchard Park, New York 14127
Contact:
Kelly Wettstein
kwettstein@circuitclinical.com

James J Peters VA Medical Center
The Bronx, New York 10468
Contact:
Kathleen Escoto
+17185849000#6667
Kathleen.escoto@va.gov

Arthritis and Rheumatology Ins
Allen, Texas 75013
Contact:
Samina Shehzad
shehzad.s@dfwarthritis.com

Liberty Research Center
Dallas, Texas 75230
Contact:
Veronica Almanza
972-274-5555
valmanza@dallasrenalgroup.com

Univof Texas Southwestern Med Cntr
Dallas, Texas 75235

Uni of Texas Health Science Center
San Antonio, Texas 78229
Contact:
Jose Restrepo
210-617-5111
restreposuar@uthscsa.edu

Baylor Scott and White Research
Temple, Texas 76502
Contact:
Sandy Owings
254-935-5838
sandy.owings@bswhealth.org

Northern Assoc of Northern VA
Fairfax, Virginia 22033
Contact:
Musirah Khan
703-953-0155
Musirah.khan@nanvonline.com

Uni Wisconsin School Med Pub Health
Madison, Wisconsin 53792
Contact:
Kian Djamali
kdjamali@clinicaltrials.wisc.edu

More Details

NCT ID
NCT05126277
Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

Detailed Description

This trial will evaluate the efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or ianalumab given every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous). using the 2003 International Society for Nephrology (ISN)/Renal Pathology Society (RPS) criteria).