Ravulizumab for Lupus Nephritis and IgA Nephropathy
(SANCTUARY Trial)
Recruiting in Palo Alto (17 mi)
+128 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Alexion Pharmaceuticals
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This trial is testing the safety and effectiveness of a drug called ravulizumab, given through a vein, in patients with specific kidney diseases. The drug aims to reduce kidney damage by blocking part of the immune system.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop your current medications. However, if you are in the IgAN cohort, you must have been on a stable dose of renin-angiotensin system inhibitors for at least 3 months. Also, you cannot have taken prednisone over 20 mg per day for more than 14 days or any other immunosuppressants within 6 months.
What data supports the idea that Ravulizumab for Lupus Nephritis and IgA Nephropathy is an effective treatment?
The available research does not provide specific data on Ravulizumab for Lupus Nephritis and IgA Nephropathy. Instead, it focuses on another drug, Belimumab, which has shown some effectiveness in treating Lupus Nephritis. Belimumab was found to reduce the risk of kidney-related events and improve kidney function in some patients. However, there is no direct comparison or data available for Ravulizumab in the provided information.12345
What safety data exists for Ravulizumab in treating Lupus Nephritis and IgA Nephropathy?
The provided research does not contain specific safety data for Ravulizumab (also known as Ultomiris, ravulizumab-cwvz, ALXN1210) in the treatment of Lupus Nephritis and IgA Nephropathy. The studies mentioned focus on other treatments such as Belimumab, Tacrolimus, and Rituximab for Lupus Nephritis. Further research or clinical trial data specific to Ravulizumab would be needed to answer this question.12678
Is the drug Ravulizumab a promising treatment for Lupus Nephritis and IgA Nephropathy?
Eligibility Criteria
This trial is for people with severe kidney inflammation due to Lupus Nephritis (LN) or IgA Nephropathy (IgAN). Participants must have protein in their urine and be vaccinated against certain infections. Those with LN need active disease treatment, while those with IgAN should be on stable blood pressure medication. People can't join if they have very low kidney function, used complement inhibitors before, have other major kidney diseases, uncontrolled high blood pressure, or recent heavy use of steroids/immunosuppressants.Inclusion Criteria
I have been diagnosed with primary IgA nephropathy.
I have been vaccinated against meningitis.
I am vaccinated for Hib and pneumonia as required.
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Exclusion Criteria
I have been diagnosed with a quickly worsening kidney condition.
I do not have significant kidney disease other than lupus nephritis or IgA nephropathy.
My kidney function is low, with an eGFR under 30.
See 4 more
Treatment Details
Interventions
- Background Therapy (Other)
- Ravulizumab (Monoclonal Antibodies)
Trial OverviewThe study tests Ravulizumab's safety and effectiveness compared to a placebo in patients with LN or IgAN. All participants will continue their usual treatments too. Ravulizumab is given through an IV infusion to see if it can help by blocking part of the immune system that damages the kidneys.
Participant Groups
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Ravulizumab: LN CohortExperimental Treatment2 Interventions
Eligible participants will receive ravulizumab IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care.
Group II: Ravulizumab: IgAN CohortExperimental Treatment2 Interventions
Eligible participants will receive ravulizumab IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care.
Group III: Placebo: LN CohortPlacebo Group2 Interventions
Eligible participants will receive placebo IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care.
Group IV: Placebo: IgAN CohortPlacebo Group3 Interventions
Eligible participants will receive placebo IV infusion in combination with background therapy during the Initial Evaluation Period (26 weeks) and will switch to ravulizumab for the Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care.
Ravulizumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Ultomiris for:
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Atypical hemolytic uremic syndrome (aHUS)
🇪🇺 Approved in European Union as Ultomiris for:
- Paroxysmal nocturnal haemoglobinuria (PNH)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteLos Angeles, CA
Research SiteMilwaukee, WI
Research SiteQuebec, Canada
Research SitePlantation, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Alexion PharmaceuticalsLead Sponsor
AlexionLead Sponsor
Alexion Pharmaceuticals, Inc.Lead Sponsor
References
Effect of Belimumab on Preventing de novo Renal Lupus Flares. [2023]Label="Introduction" NlmCategory="UNASSIGNED">Belimumab was recently approved for treating lupus nephritis (LN), yet de novo LN cases during belimumab treatment given for nonrenal causes have been reported. Identification of reliable signals of impending flare is imperative.
Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial. [2023]Data on belimumab efficacy in patients with lupus nephritis (LN) according to diagnosis duration or induction therapy are limited. Post hoc analyses of the phase 3, randomized, double-blind BLISS-LN study (GSK BEL114054; NCT01639339) were performed to assess belimumab efficacy on kidney-related outcomes in newly diagnosed and relapsed LN subgroups and according to the use of glucocorticoid (GC) pulses at induction.
A secondary analysis of the Belimumab International Study in Lupus Nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis. [2022]We performed a post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). Add-on belimumab was found to be most effective in improving the primary efficacy kidney response and complete kidney response in patients with proliferative lupus nephritis and a baseline urine protein/creatinine ratio under 3 g/g. However, there was no observed improvement in the kidney response with belimumab treatment in patients with lupus nephritis and sub-epithelial deposits or with a baseline protein/creatinine ratio of 3 g/g or more. Belimumab significantly reduced the risk of kidney-related events or death and lupus nephritis flare in the overall population. Belimumab reduced the risk of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) versus standard treatment alone and attenuated the annual rate of eGFR decline in patients who remained on-study. Thus, our data suggest that the addition of belimumab to standard therapy could attenuate the risk of lupus nephritis flare and eGFR decline in a broad spectrum of patients with lupus nephritis.
Response to belimumab among patients with refractory lupus nephritis: a real-world observational retrospective multicenter study. [2023]Belimumab is a biological agent approved for the treatment of active lupus nephritis (LN), but its efficacy on refractory lupus nephritis (LN) is unknown. This study aims to evaluate the efficacy and safety of belimumab in Chinese patients with refractory LN.
Effect of belimumab treatment on renal outcomes: results from the phase 3 belimumab clinical trials in patients with SLE. [2016]A pooled post-hoc analysis of the phase 3, randomized, placebo-controlled BLISS trials (1684 patients with active systemic lupus erythematosus (SLE)) was performed to evaluate the effect of belimumab on renal parameters in patients with renal involvement at baseline, and to explore whether belimumab offered additional renal benefit to patients receiving mycophenolate mofetil at baseline. In addition to belimumab or placebo, all patients received standard SLE therapy. Patients with severe active lupus nephritis were excluded from the trials. Over 52 weeks, rates of renal flare, renal remission, renal organ disease improvement (assessed by Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group), proteinuria reduction, grade 3/4 proteinuria, and serologic activity favored belimumab, although the between-group differences in most renal outcomes were not significant. Among the 267 patients with renal involvement at baseline, those receiving mycophenolate mofetil or with serologic activity at baseline had greater renal organ disease improvement with belimumab than with placebo. Limitations of this analysis included the small patient numbers and the post-hoc nature of this pooled analysis. The results suggest that belimumab may offer renal benefit in patients with SLE. Further study is warranted in patients with severe active lupus nephritis.
Long-term Safety and Effectiveness of Tacrolimus in Patients With Lupus Nephritis: 5-year Interim Postmarketing Surveillance Study in Japan (TRUST). [2021]To assess the long-term safety and effectiveness of tacrolimus for treating lupus nephritis (LN) in the real-world clinical setting.
Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis. [2022]To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN).
Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort. [2022]Belimumab was recently approved for treatment of lupus glomerulonephritis (LN).
Coexistence of atypical hemolytic uremic syndrome and crescentic IgA nephropathy treated with eculizumab: a case report. [2020]Rapid progression to end-stage renal disease has been reported in a minority of patients with immunoglobulin A (IgA) nephropathy. In particular, crescentic IgA nephropathy has a poor prognosis in patients with a higher initial serum creatinine level. The complement system plays an important role in the pathogenesis of crescentic IgA nephropathy. Atypical hemolytic uremic syndrome (aHUS), which is characterized by thrombotic microangiopathy, is distinct from Shigatoxin-induced HUS and thrombotic thrombocytopenic purpura. aHUS is associated with dysregulation of the alternative complement system. Eculizumab, an anti-C5 antibody, is effective in limiting complement activation in patients with paroxysmal nocturnal hemoglobinuria, aHUS, or refractory IgA nephropathy in some case reports. We herein report the case of a 42-year-old man with acute kidney injury (AKI) clinically and histologically diagnosed with the coexistence of aHUS and crescentic IgA nephropathy. The patient was treated with steroids, plasmapheresis, and hemodialysis; however, eculizumab treatment was initiated on hospital day 21 due to resistance to and dependence on the conventional aggressive therapy. Clinical remission of aHUS was achieved on day 70, but the renal function failed to recover from dialysis dependence. To the best of our knowledge, this is the first report showing the clinical course of a refractory patient with the coexistence of aHUS and crescentic IgA nephropathy treated with eculizumab. This case highlights the clinical importance of early diagnosis and appropriate initiation of eculizumab for the treatment of this type of AKI.
Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum? [2022]IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement.
Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases. [2018]Rituximab is a monoclonal antibody to the CD20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin's B-cell lymphoma in 1997. In the last 15years, it has emerged as a potent immunosuppressant for many immune-mediated diseases, beginning initially with rheumatoid arthritis, and now extending into several other fields, including clinical nephrology. Based on recent large clinical trials, it is FDA-approved for the treatment of ANCA-associated vasculitis and continues to be studied in off-label usage for many glomerular diseases, including membranous nephropathy, lupus nephritis, and mixed cryoglobulinemia. It has been used as a treatment in nephrotic syndrome in children and adults, including both minimal change disease and focal segmental glomerulosclerosis. Given its efficacy, tolerability and safety profile in comparison to more conventional treatment regimens, RTX is rapidly emerging as a critical treatment modality in glomerular disease.
Efficacy and safety of an anti-CD20 monoclonal antibody, rituximab, for lupus nephritis: A meta-analysis. [2022]The efficacy and safety of rituximab (RTX) for lupus nephritis are still a controversial issue.