Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis
- Conditions
- Lupus Nephritis
- Interventions
- Registration Number
- NCT05126277
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 420
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
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Weigh at least 35 kg at screening
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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
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Have a positive anti-nuclear antibody (ANA) test result; ANA titer ≥ 1:80 at screening visit based on central or local laboratory result
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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
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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
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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.
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Able to communicate well with the Investigator to understand and comply with the requirements of the study
Participants meeting any of the following criteria are not eligible for inclusion in this study:
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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
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Sclerosis in > 50% of glomeruli on renal biopsy
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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
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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
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Imidazole derivative (e.g., azathioprine, mizoribine) must be discontinued prior to starting treatment with MPA
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Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within 12 weeks prior to randomization
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History of major organ transplant or hematopoietic stem cell/bone marrow transplant or are due to receive transplantation
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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
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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.
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History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component of the study drug(s) or its excipients
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Receipt of live/attenuated vaccine within a 4-week period prior to randomization
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History of primary or secondary immunodeficiency, including a positive HIV test result
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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
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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
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Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis B surface antigen (HBsAg) excludes the participant
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Evidence of active tuberculosis (TB) infection (after anti-TB treatment, participants with history of TB may become eligible according to national local guidelines)
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Pregnant or nursing (lactating) women
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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
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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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 - ianalumab s.c. q4w ianalumab s.c. q4w ianalumab s.c. q4w in addition to standard of care (SoC) Arm 3 - placebo s.c. q4w placebo s.c. Placebo s.c. q4w in addition to SoC Arm 2 - ianalumab s.c. q12w ianalumab s.c. q12w ianalumab s.c. q12w in addition to SoC
- Primary Outcome Measures
Name Time Method Frequency and percentage of participants achieving stable Complete Renal Response (CRR) Week 72 The primary objective is to demonstrate superiority of ianalumab compared to placebo, in achieving stable CRR (defined as estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m2 or no less than 85% of baseline, AND, 24-hour UPCR \<0.5 g/g) at Week 72 in active lupus nephritis (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous) participants on background SoC therapy.
- Secondary Outcome Measures
Name Time Method Time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) <0.5 g/g or ≥50% reduction from baseline Week 72 To demonstrate superiority of ianalumab, compared to placebo, in time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) \<0.5 g/g or ≥50% reduction from baseline up to Week 72
Percentage of participants achieving stable Overall Renal Response (ORR), defined as achievement as either Complete Renal Response (CRR) or Partial Renal Response (PRR) Week 48 To demonstrate superiority of ianalumab, compared to placebo, in achieving stable Overall Renal Response (ORR) at Week 48
Number of participants with treatment-emergent Adverse Events (AEs) Week 72 AEs are any untoward sign or symptom that occurs during the study treatment
Ianalumab concentration in serum Week 72 To characterize the pharmacokinetics (PK) of ianalumab mean, median, minimum and maximum concentrations will be provided
Incidence of stable Complete Renal Response (CRR) while maintaining daily corticosteroid dose ≤5 mg/day Week 72 To demonstrate superiority of ianalumab, compared to placebo, in achieving stable Complete Renal Response (CRR) at Week 72 while maintaining daily corticosteroid dose ≤5 mg/day between Week 24 and Week 72
Incidence of renal-related event or death Week 72 To demonstrate superiority of ianalumab, compared to placebo, in preventing renal-related event or death through Week 72
Change in British Isles Lupus Activity Group (BILAG) score Week 72 To demonstrate superiority of ianalumab, compared to placebo in BILAG-2004 at Week 72
Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score Week 72 To demonstrate superiority of ianalumab, compared to placebo, in FACIT-Fatigue at Week 72
Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time Week 72 To evaluate immunogenicity of ianalumab
Trial Locations
- Locations (34)
University Of Alabama
🇺🇸Birmingham, Alabama, United States
Wallace Rheumatic Study Center
🇺🇸Los Angeles, California, United States
University of California LA
🇺🇸Los Angeles, California, United States
University of California Irvine
🇺🇸Orange, California, United States
UC Davis School of Medicine
🇺🇸Sacramento, California, United States
University of California San Diego
🇺🇸San Diego, California, United States
Kaiser Permanente
🇺🇸San Diego, California, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
University Of Miami
🇺🇸Miami, Florida, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Fides Clinical Research
🇺🇸Atlanta, Georgia, United States
Parris and Associates Rheumatology
🇺🇸Lawrenceville, Georgia, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
UMC New Orleans
🇺🇸New Orleans, Louisiana, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Univ of Nevada School of Med
🇺🇸Las Vegas, Nevada, United States
Sahni Rheumatology and Therapy
🇺🇸West Long Branch, New Jersey, United States
VA NM Healthcare System
🇺🇸Albuquerque, New Mexico, United States
James J Peters VA Medical Center
🇺🇸Bronx, New York, United States
NY Nephrology
🇺🇸Clifton Park, New York, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Northwell Health
🇺🇸New York, New York, United States
Circuit Clinical
🇺🇸Orchard Park, New York, United States
Brookview Hills Research Assoc
🇺🇸Winston-Salem, North Carolina, United States
University Of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Univ of Pennsylvania Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Liberty Research Center
🇺🇸Dallas, Texas, United States
Univof Texas Southwestern Med Cntr
🇺🇸Dallas, Texas, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Uni of Texas Health Science Center
🇺🇸San Antonio, Texas, United States
Baylor Scott and White Research
🇺🇸Temple, Texas, United States
Northern Assoc of Northern VA
🇺🇸Fairfax, Virginia, United States
Uni Wisconsin School Med Pub Health
🇺🇸Madison, Wisconsin, United States
Novartis Investigative Site
🇻🇳Ho Chi Minh, Vietnam