Henoch-schonlein Purpura Nephritis, IgAN, IgA Vasculitis, IgAVN, Immunoglobulin A Nephropathy, Immunoglobulin A Vasculitis Associated Nephritis
Conditions
Keywords
ravulizumab, IgAN, IgAVN, pediatric, proteinuria, glomerulonephropathy, Immunoglobulin A Nephropathy, Immunoglobulin A Vasculitis Associated Nephritis
Brief summary
The primary objectives of this study are to characterize ravulizumab pharmacokinetics (PK) and pharmacodynamics (PD), and to evaluate safety and efficacy following ravulizumab IV dosing in pediatric participants with IgAN or IgAVN.
Interventions
DRUGRavulizumab
Participants will receive Ravulizumab via intravenous (IV) infusion.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
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 RAASI (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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline in Proteinuria Based on Urine Protein to Creatinine Ratio (UPCR) at Week 34 | Baseline, Week 34 |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Ravulizumab | Baseline up to Week 34 |
| Trough Serum Concentration (Ctrough) of Ravulizumab | Baseline up to Week 34 |
| Change From Baseline in Serum Free Complement Component 5 (C5) Concentration | Baseline up to Week 34 |
| Change from Baseline in proteinuria based on Urine Protein to Creatinine Ratio (UPCR) at Week 10 | Baseline, Week 10 |
| Change from Baseline in Albuminuria based on Urine Albumin to Creatinine Ratio (UACR) at Week 34 | Baseline, Week 34 |
| Number of Participants with Partial Remission | Week 34 |
| Annualized Total Estimated Glomerular Filtraion Rate (eGFR) over 106 weeks | Baseline up to Week 106 |
| Change from Baseline in eGFR | Baseline, Weeks 50 and 106 |
| Number of Participants with UPCR <0.5 gram of protein per gram of creatinine | Week 34 |
| Number of Participants With Treatment Emergent Adverse Events, Treatment Emergent Serious Adverse Events and Adverse Events of Special Interest | Baseline up to Week 106 |
| Number of Participants with Antidrug Antibodies to Ravulizumab and Neutralizing Antibodies | Baseline up to Week 106 |
Countries
China, Italy, Japan, South Korea, Spain, Taiwan, United States
Contacts
CONTACTAlexion Pharmaceuticals, Inc. (Sponsor)
Outcome results
None listed