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

Study 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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05126277
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Novartis Pharmaceuticals
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Novartis Pharmaceuticals
Principal Investigator Affiliation	Novartis Pharmaceuticals
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Brazil, Canada, Chile, China, Colombia, Czechia, Estonia, France, Germany, Guatemala, Hong Kong, Hungary, India, Italy, Lithuania, Malaysia, Mexico, Romania, Singapore, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States, Vietnam
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Lupus Nephritis

Additional Details

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).

Arms & Interventions

Arms

Experimental: Arm 1 - ianalumab s.c. q4w

ianalumab s.c. q4w in addition to standard of care (SoC)

Experimental: Arm 2 - ianalumab s.c. q12w

ianalumab s.c. q12w in addition to SoC

Placebo Comparator: Arm 3 - placebo s.c. q4w

Placebo s.c. q4w in addition to SoC

Interventions

Drug: - ianalumab s.c. q4w

ianalumab s.c. q4w in addition to SoC

Drug: - ianalumab s.c. q12w

ianalumab s.c. q12w in addition to SoC

Drug: - placebo s.c.

placebo s.c. q4w in addition to SoC

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University Of Alabama, Birmingham 4049979, Alabama 4829764

Status

Recruiting

Address

University Of Alabama

Birmingham 4049979, Alabama 4829764, 35294

Site Contact

Jane Vines

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