Ravulizumab for children with IgA nephropathy or IgA vasculitis nephritis

A Phase 3, Open-Label, Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Ravulizumab in Pediatric Participants (2 to < 18 Years of Age) With Primary Immunoglobulin A Nephropathy (IgAN)

This trial will test whether intravenous ravulizumab is safe and changes disease markers in children aged 2 to under 18 with biopsy‑proven IgA nephropathy or IgA vasculitis nephritis.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 2 Years to 18 Years
• Sex: All
• Sponsor: Alexion Pharmaceuticals, Inc. (Industry-sponsored)
• Drugs / interventions: ravulizumab
• Locations: 14 sites (Palo Alto, California and 13 other locations)
• Trial ID: NCT07024563 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional study gives intravenous ravulizumab to pediatric participants to characterize pharmacokinetics and pharmacodynamics and to monitor safety and signs of efficacy. Eligible children have biopsy‑proven primary IgA nephropathy or IgA vasculitis nephritis, proteinuria (UPCR ≥ 1.0 g/g), and estimated GFR ≥ 30 mL/min/1.73 m2 and must be on stable RAAS blockade. Dosing and follow‑up include repeated clinic visits and laboratory assessments over an extended period (protocol references include stability requirements through Week 34 and Week 106). Vaccination against meningococcus, Haemophilus influenzae type b, and Streptococcus pneumoniae is required prior to dosing and participants must be able to attend one of the participating study sites.

Who should consider this trial

Good fit: Children aged 2 to <18 years with biopsy‑proven primary IgA nephropathy or IgA vasculitis nephritis within the prior 3 years, UPCR ≥ 1.0 g/g, eGFR ≥ 30 mL/min/1.73 m2, on a stable maximum tolerated RAAS inhibitor dose, and up to date on required vaccinations are ideal candidates.

Not a fit: Patients with rapidly progressive glomerulonephritis, eGFR < 30 mL/min/1.73 m2, low proteinuria below the entry threshold, secondary causes of IgA disease, or who cannot receive required vaccinations are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, ravulizumab could offer a new treatment option that reduces proteinuria and slows kidney injury in children with IgA nephropathy or IgA vasculitis nephritis.

How similar studies have performed: Complement C5 inhibition (the mechanism of ravulizumab) is an established therapy for other rare diseases but remains an experimental and relatively novel approach in IgA nephropathy, with limited or mixed early clinical data to date.

Eligibility criteria

Inclusion Criteria:

* Participant must be 2 to \< 18 years of age at the time of signing the informed consent or assent.
* Stable and maximum allowed or tolerated RASI (ACEI and/or ARB) dose for ≥ 3 months prior to Screening with no planned change during Screening through Week 106.
* UPCR ≥ 1.0 g/g from the mean of 3 first morning voids (FMV) collected within 1 week during the Screening Period
* Estimated GFR ≥ 30 mL/min/1.73 m2 during Screening
* Meningococcal infection vaccine
* Haemophilus influenzae type b and Streptococcus pneumoniae vaccine
* Participants who are receiving SGLT2i, DEARA (eg, sparsentan), MRA, ERA, or GLP-1 agonists must be on a stable and maximum allowed or tolerated dose for ≥ 3 months prior to Screening with no planned change in dose through Week 34.
* Established diagnosis of primary IgAN diagnosis based on kidney biopsy within 3 years prior to Screening or during the Screening Period

Exclusion Criteria:

* Diagnosis of rapidly progressive glomerulonephritis
* Secondary forms of IgAN not in the context of primary IgAN or IgAV
* Concomitant clinically significant renal disease other than IgAN or IgAVN
* Clinical remission of IgAN/IgAVN or clinically significant improvement in proteinuria within the last 6 months.
* Uncontrolled diabetes mellitus with HbA1c \> 8.5%
* History of kidney transplant or planned kidney transplant during the Primary Evaluation Period.
* History of other solid organ (heart, lung, small bowel, pancreas, or liver) or bone marrow transplant
* Splenectomy or functional asplenia
* Participants with nephrotic syndrome receiving albumin infusions or with acute kidney injury requiring dialysis within the last 6 months prior to Screening.
* Hemolytic uremic syndrome diagnosed any time prior to Screening.
* Planned urological surgery expected to influence kidney function within the study time frame.
* Congenital immunodeficiency
* Active systemic bacterial, viral, or fungal infection within 14 days prior to enrollment
* Received biologics for the treatment of IgAN or IgAVN within≤ 6 months prior to Screening

Where this trial is running

Palo Alto, California and 13 other locations

• Research Site — Palo Alto, California, United States (Not_yet_recruiting)
• Research Site — Aurora, Colorado, United States (Recruiting)
• Research Site — Beijing, China (Recruiting)
• Research Site — Shanghai, China (Recruiting)
• Research Site — Genova, Italy (Recruiting)
• Research Site — Roma, Italy (Recruiting)
• Research Site — Torino, Italy (Recruiting)
• Research Site — Wakayama, Japan (Recruiting)
• Research Site — Seoul, South Korea (Recruiting)
• Research Site — Barcelona, Spain (Recruiting)
• Research Site — Barcelona, Spain (Recruiting)
• Research Site — Seville, Spain (Recruiting)
• Research Site — Taipei, Taiwan (Recruiting)
• Research Site — Taoyuan, Taiwan (Recruiting)

Study contacts

• Study coordinator: Alexion Pharmaceuticals, Inc. (Sponsor)

Conditions IgAN; IgAVN; Immunoglobulin A Nephropathy; Immunoglobulin A Vasculitis Associated Nephritis; Henoch-schonlein Purpura Nephritis; IgA Vasculitis; ravulizumab; pediatric