Ravulizumab for Kidney Disease
(ICAN Trial)
Recruiting in Palo Alto (17 mi)
+259 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Alexion Pharmaceuticals, Inc.
Must be taking: RASI, SGLT2I
Must not be taking: Immunosuppressives
Disqualifiers: Rapid glomerulonephritis, Secondary IgAN, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The primary objective of this study to evaluate efficacy of ravulizumab compared with placebo on proteinuria reduction and change in eGFR in adult participants with IgAN who are at risk of disease progression.
Do I need to stop my current medications to join the trial?
The trial requires that you stay on a stable dose of certain medications like RASI (ACEI and/or ARB), SGLT2I, DEARA, MRA, or ERA for at least 3 months before and throughout the trial. If you're on these medications, you won't need to stop them.
How is the drug Ravulizumab unique for treating kidney disease?
Ravulizumab is unique because it is a long-acting drug that inhibits complement protein C5, allowing for less frequent dosing (once every 4-8 weeks) compared to similar treatments like eculizumab, which requires dosing every 2-3 weeks. This extended dosing schedule can make treatment more convenient for patients.
12345Eligibility Criteria
This trial is for adults with IgA Nephropathy, a kidney disease causing protein in urine and kidney function decline. Participants should be at risk of their condition getting worse.Inclusion Criteria
My kidney function is low and I've had a kidney biopsy in the last 6 months.
UPCR ≥ 0.75 g/g or UP ≥1 g/day from the mean of two 24-hour urine collections during Screening
Documentation of IgAN diagnosis established on kidney biopsy obtained any time prior to or during the Screening Period
+4 more
Exclusion Criteria
I haven't taken immunosuppressive drugs for IgAN in the last 6 months.
My kidney function has rapidly declined by half or more in the last 3 months.
I have had a kidney transplant or will have one soon.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
3 months
Treatment
Participants receive a weight-based IV infusion of either ravulizumab or placebo every 8 weeks
106 weeks
Visits every 8 weeks for infusion
Interim Analysis
Interim analysis conducted to evaluate change in proteinuria and eGFR
34 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Open-label extension
Participants have the option to enter an Open-label Ravulizumab Access Period
Participant Groups
The study tests if Ravulizumab can better reduce proteinuria (protein in urine) and slow down the loss of kidney function compared to a placebo in patients with IgAN.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Ravulizumab IV q8wExperimental Treatment1 Intervention
Participants will receive a weight-based loading dose on Day 1 followed by weight-based maintenance dosing initiated on Day 15, and then administered every 8 weeks (q8w).
Group II: Placebo IV q8wPlacebo Group1 Intervention
Participants will receive a weight-based loading dose on Day 1 followed by weight-based maintenance dosing initiated on Day 15, and then administered q8w.
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 SiteArlington, TX
Research SiteWinnipeg, Canada
Research SiteLoma Linda, CA
Research SiteTorrance, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Alexion Pharmaceuticals, Inc.Lead Sponsor
References
Ravulizumab: First Global Approval. [2020]Ravulizumab (ravulizumab-cwvz; ULTOMIRIS™), a humanized monoclonal antibody, is a complement C5 inhibitor developed by Alexion Pharmaceuticals for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS). Like the first-generation C5 inhibitor, eculizumab, ravulizumab binds specifically and with high affinity to the complement protein C5, thereby preventing formation of the terminal complement complex C5b-9, which mediates cell lysis. In December 2018, intravenous ravulizumab received its first global approval in the USA for the treatment of adults with PNH, and is under regulatory review in the European Union and Japan in this indication. Phase 3 development of intravenous ravulizumab for the treatment of aHUS is underway worldwide. The use of ravulizumab in myasthenia gravis and IgA nephropathy is also being evaluated in the USA in early-phase and preclinical studies, respectively. Clinical development of a subcutaneous formulation for PNH and aHUS is also underway. Ravulizumab has been developed using Xencor's antibody half-life prolongation technology (Xtend™), which utilises antibody Fc variants to prolong half-life. Alexion is also evaluating the coadministration of subcutaneous ravulizumab with Halozyme's ENHANZE® drug-delivery technology (rHuPH20), which may have the potential to further extend the dosing interval. This article summarizes the milestones in the development of ravulizumab leading to this first approval for PNH.
Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults. [2022]Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic kidney disease. Results from the prospective clinical trial of ravulizumab (NCT02949128) reveal rapid resolution of TMA in patients with aHUS, with sustained efficacy and safety in a 26-week initial evaluation period.
Ravulizumab: Characterization and quantitation of a new C5 inhibitor using isotype specific affinity purification and high-resolution mass spectrometry. [2022]Ravulizumab (RAVUL) is a new complement inhibitor, with a difference of 4 amino acids in the heavy chain from a predecessor compound, eculizumab (ECUL).
Evaluation of Eculizumab Use in Renal Transplant Recipients. [2023]Introduction: Eculizumab is a monoclonal antibody that binds to complement protein C5, inhibiting complement-mediated thrombotic microangiopathy. It is approved for several indications including atypical hemolytic uremic syndrome. Additionally, eculizumab is used off-label for antibody-mediated rejection and C3 glomerulopathy in renal transplant recipients. Due to limited data available, the purpose of this study was to describe the use of eculizumab treatment in renal transplant recipients. Design: This retrospective single-center study evaluated the safety and efficacy of eculizumab for on- and off-label indications in renal transplant recipients. Adult renal transplant recipients receiving at least 1 dose of eculizumab posttransplant between October 2018 and September 2021 were included. The primary outcome evaluated was graft failure in patients treated with eculizumab. Results: Forty-seven patients were included in analysis. The median age at eculizumab initiation was 51 years [IQR 38-60], with 55% being female. Indications for eculizumab included atypical hemolytic uremic syndrome/thrombotic microangiopathy (63.8%), antibody-mediated rejection (27.7%), C3 glomerulopathy (4.3%), and other (4.3%). Graft failure occurred in 10 patients (21.3%) with a median of 2.4 weeks [IQR 0.5-23.3] from transplant to graft failure. At last follow-up (median 56.1 weeks), 44 (93.6%) patients were alive. After eculizumab initiation, renal function improved at 1 week, 1 month, and last follow-up. Conclusion: Eculizumab treatment demonstrated a benefit on graft and patient survival compared to reported incidence in thrombotic microangiopathy and antibody-mediated rejection. Due to the small sample size and retrospective design, further research is warranted to confirm these results.
Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome. [2022]Ravulizumab (Ultomiris®), a humanized monoclonal antibody that inhibits complement protein C5, is indicated for the treatment of atypical haemolytic uraemic syndrome (aHUS) in several countries, including the USA and those of the EU. Ravulizumab has been re-engineered from eculizumab to extend its terminal elimination half-life, resulting in a more convenient maintenance dosage regimen of once every 4-8 weeks compared with once every 2-3 weeks for eculizumab. In single-arm phase 3 trials, ravulizumab resolved thrombotic microangiopathy in 54% and 78% of treatment-naïve adult and paediatric patients with aHUS, respectively, within 26 weeks. Ravulizumab was also effective in patients with postpartum aHUS and paediatric patients who responded to eculizumab and later switched to ravulizumab. Ravulizumab was generally well tolerated, with no unexpected safety events. The most common treatment-related adverse events with ravulizumab in treatment-naïve patients include headache, diarrhoea and vomiting. With its convenient once every 4-8 weeks maintenance regimen, ravulizumab is an important treatment option for aHUS in adult and paediatric patients.