Ravulizumab for Kidney Disease

(ICAN Trial)

Recruiting at 235 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

Trial Summary

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. ^{1 2 3 4 5}

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.

Eligibility 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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 (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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ravulizumab: First Global Approval. [2020]

2. United States 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. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Eculizumab Use in Renal Transplant Recipients. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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