Ravulizumab for Kidney Disease

(ICAN Trial)

Recruiting at 284 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion Pharmaceuticals, Inc.

Must be taking: RASI, SGLT2I

Must not be taking: Immunosuppressives

Disqualifiers: Rapid glomerulonephritis, Secondary IgAN, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 106 weeks

510 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a drug called ravulizumab for individuals with IgA nephropathy (IgAN), a kidney disease that can lead to kidney failure. Researchers aim to determine if this treatment can reduce protein in the urine and improve kidney function compared to a placebo. Participants will receive either ravulizumab or a placebo through an IV every eight weeks. The trial seeks individuals diagnosed with IgAN through a kidney biopsy who have maintained a certain level of kidney function and consistent medication for at least three months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that ravulizumab is likely to be safe for humans?

Studies have shown that ravulizumab is generally safe for adults. Research indicates that it is well-tolerated over long periods. For example, patients who took ravulizumab every 8 weeks for several years mostly experienced mild to moderate side effects. The most common side effects included headaches and upper respiratory infections, affecting more than 10% of patients. These findings come from studies on conditions like atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH), which are similar to the current trial for kidney disease. Notably, the FDA has approved ravulizumab for other conditions, indicating it has met certain safety standards. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney disease?

Ravulizumab is unique because it offers a novel approach to treating kidney disease by targeting the complement system, specifically inhibiting the C5 protein. This is different from most current treatments, which often focus on managing symptoms rather than addressing underlying immune processes. Additionally, Ravulizumab is administered intravenously every 8 weeks, providing a more convenient dosing schedule compared to some treatments that require more frequent administration. Researchers are excited about Ravulizumab because it has the potential to improve patient outcomes by directly intervening in the disease process with less frequent treatments.

What evidence suggests that ravulizumab might be an effective treatment for kidney disease?

Research has shown that ravulizumab, which participants in this trial may receive, may help treat IgA nephropathy (IgAN), a kidney disease. In studies, patients taking ravulizumab experienced a noticeable decrease in protein in their urine, indicating reduced kidney damage. Additionally, there was a trend toward stabilizing eGFR, a measure of kidney function, suggesting that ravulizumab could slow the disease's progression. Long-term use has proven to be well tolerated, with continued improvements in kidney function. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ravulizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Ravulizumab IV q8w Experimental Treatment 1 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 q8w Placebo Group 1 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)

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Published Research Related to This Trial

Ravulizumab (RAVUL) was successfully characterized and differentiated from its predecessor, eculizumab (ECUL), using time-of-flight mass spectrometry (TOF-MS), confirming their molecular weight differences.

A validated lab-developed test (LDT) for RAVUL was implemented, allowing for quantitative therapeutic monitoring with a measuring range of 5 to 600 mcg/mL and high accuracy, although it cannot distinguish between RAVUL and ECUL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: Characterization and quantitation of a new C5 inhibitor using isotype specific affinity purification and high-resolution mass spectrometry. Ladwig, PM., Willrich, MAV.[2022]

In a study of 47 renal transplant recipients treated with eculizumab, the treatment showed a positive impact on graft survival and patient survival, with 93.6% of patients alive at the last follow-up after a median of 56.1 weeks.

Eculizumab led to improvements in renal function at multiple time points post-treatment, suggesting its efficacy in managing complications like atypical hemolytic uremic syndrome and antibody-mediated rejection, although further research is needed due to the small sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Eculizumab Use in Renal Transplant Recipients. Norville, K., Stephen, J., Mead-Harvey, C., et al.[2023]

Ravulizumab is a monoclonal antibody that inhibits complement C5, effectively preventing cell lysis in conditions like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), and received its first approval in the USA in December 2018 for treating adults with PNH.

The drug has been developed using technology to extend its half-life, allowing for less frequent dosing, and is currently being evaluated for additional uses in myasthenia gravis and IgA nephropathy, as well as a subcutaneous formulation for easier administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: First Global Approval. McKeage, K.[2020]

Ravulizumab has shown long-term efficacy in treating atypical hemolytic uremic syndrome (aHUS), with a median follow-up of 76.7 weeks revealing sustained improvements in thrombotic microangiopathy (TMA) and kidney function in 58 patients.

The treatment demonstrated an acceptable safety profile, with most adverse events occurring early in the treatment and no cases of meningococcal infection or death during the follow-up period, indicating it is a safe option for long-term management of aHUS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults. Barbour, T., Scully, M., Ariceta, G., et al.[2022]

Ravulizumab is an effective treatment for atypical hemolytic uremic syndrome (aHUS), resolving thrombotic microangiopathy in 54% of adult and 78% of pediatric treatment-naïve patients within 26 weeks, making it a promising option for both groups.

With a maintenance dosage of once every 4-8 weeks, ravulizumab offers a more convenient treatment schedule compared to its predecessor eculizumab, which requires dosing every 2-3 weeks, while maintaining a good safety profile with common side effects like headache and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome. Syed, YY.[2022]

Citations

1. ultomirishcp.com ultomirishcp.com/pnh/efficacy-and-safety/adult-data

PNH | Adult data - ULTOMIRIS® (ravulizumab-cwvz) In patients receiving ULTOMIRIS, LDH levels rapidly fell below 1.5 x ULN by Week 2, normalized by Week 4, and were maintained below 1.5 x ULN through 5.6 years.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40448185/

A phase 3 study of ravulizumab to protect patients with ... This is a phase 3, randomized, double-blind, placebo-controlled, global study assessing the efficacy and safety of a single preoperative dose of ravulizumab.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8207473/

Long-Term Efficacy and Safety of the ... This analysis of longer-term treatment with ravulizumab reveals that administration every 8 weeks is well tolerated and provides clinical improvement in kidney ...

4. ultomiris.com ultomiris.com/ahus/ultomiris-results/efficacy-in-adults-and-children

Efficacy in Adults and Children Kidney function improvement is possible ... Most people taking ULTOMIRIS saw their kidney function improve in 6 months or less and continue to maintain those ...

5. journals.lww.com journals.lww.com/jasn/fulltext/2025/04000/efficacy_and_safety_of_ravulizumab_in_iga.12.aspx

Efficacy and Safety of Ravulizumab in IgA Nephropathy An early, sustained, and clinically meaningful reduction in proteinuria and trend toward stabilization of eGFR were observed with ravulizumab versus placebo.

6. ultomirishcp.com ultomirishcp.com/ahus/considering-ultomiris/adult-efficacy-and-safety

Atypical-HUS | Adult data - ULTOMIRIS® (ravulizumab-cwvz) Changes in CKD stage. ULTOMIRIS offers 8 weeks of sustained C5 inhibition and an opportunity to discontinue dialysis in adult patients1. Patients with chronic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12125780/

A phase 3 study of ravulizumab to protect patients with chronic ... This is a phase 3, randomized, double-blind, placebo-controlled, global study assessing the efficacy and safety of a single preoperative dose of ravulizumab.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02949128

NCT02949128 | Study of ALXN1210 in Complement ... The purpose of the study is to assess the safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had ...