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)

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. To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of ravulizumab in pediatric patients (N≈18) with IgAN (cohort 1, n = 12) or IgAVN (cohort 2, n ≈ 6).

CT.gov Identifier

NCT07024563

EudraCT Identifier

N/A

CTIS:

2024-520167-13-00

Collaborator

N/A

Study Contact Information

+44 20 3749 5000

Recruiting

Study Details

Diseases

IgA nephropathy

Study Drug

Ravulizumab (iv)

Genes

N/A

Study Dates

Jun 2025 - Jul 2028

Sex

Female & Male

Age

2 - 18 Years

Inclusion and Exclusion 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 ≥ 0.5 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 vaccineParticipant 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 PeriodEstimated GFR ≥ 30 mL/min/1.73 m2 during ScreeningMeningococcal infection vaccineHaemophilus influenzae type b and Streptococcus pneumoniae vaccineParticipants 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
1. Participant must be >= 2 to < 18 years of age inclusive, at the time of signing the informed consent or assent.
2. UPCR>=1 g/g from the mean of 3 FMVs collected within 1 week during the Screening Period (should be collected at home).
3. eGFR>=30 mL/min/1.73 m2 during Screening as calculated by the CKiD U25 equation (cystatin C) (Pierce, 2021).
4. Adherence to and compliance with stable (weight-adjusted per PI's discretion) and maximum allowed or tolerated RASI (ACEI and/or ARB) dose for >= 3 months prior to Screening with no planned change in dose (weight-adjusted per PI's discretion) during Screening through Week 106. Participants with intolerance to RASI medications may be included.
5. 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.

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 * 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 ≤ 6 months prior to Screening
1. Diagnosis of rapidly progressive glomerulonephritis as measured by eGFR loss >= 50% over a period of 3 months and/or have > 50% crescents on the kidney biopsy prior to Screening.
2. Secondary forms of IgAN not in the context of primary IgAN or IgAV (eg, due to systemic lupus erythematosus, cirrhosis, or celiac disease).
3. Concomitant clinically significant renal disease other than IgAN or IgAVN.
4. Clinical remission of IgAN/IgAVN or clinically significant improvement in proteinuria within the last 6 months.
5. Uncontrolled diabetes mellitus with HbA1c > 8.5%.
6. History of kidney transplant or planned kidney transplant during the Primary Evaluation Period.
7. History of other solid organ (heart, lung, small bowel, pancreas, or liver) or bone marrow transplant; or planned transplant during the Primary Evaluation Period or Extension Period, except for corneal transplant.
8. Splenectomy or functional asplenia.
9. Participants with nephrotic syndrome receiving albumin infusions or with acute kidney injury requiring dialysis within the last 6 months prior to Screening.
10. Systemic BP criteria. If < 13 years of age: Systemic BP >= 95th percentile + 12 mm Hg for sex and height or >= 140/90 mm Hg, whichever is lower. If >= 13 years of age: Systemic BP >= 140/90 mm Hg.
11. Hemolytic uremic syndrome diagnosed any time prior to Screening.
12. Planned urological surgery expected to influence kidney function within the study time frame.
13. Congenital immunodeficiency.
14. History of unexplained, recurrent infection.
15. Known medical or psychological condition(s), including substance abuse, or risk factor that, in the opinion of the Investigator, might interfere with the participant's full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study.
16. History of or unresolved N meningitidis infection.
17. Known history of HIV, active hepatitis B infection, or active hepatitis C infection.
18. Active systemic bacterial, viral, or fungal infection within 14 days prior to enrollment.
19. Drug or alcohol abuse or dependence within 1 year prior to Screening that interferes with ability to participate in the clinical study.
20. History of malignancy within 5 years of Screening, except for nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
21. Hypersensitivity to any ingredient contained in the study intervention, including murine proteins.
22. Received biologics for the treatment of IgAN or IgAVN within 6 months prior to Screening.
23. Traditional Chinese medicines and Chinese proprietary medicines with systemic immunosuppressive properties including but not limited to Tripterygium wilfordii or Tripterygium wilfordii-containing medicines for the treatment of IgAN or IgAVN within 6 months prior to Screening.
24. Received a complement inhibitor >= 30 days or 5 half-lives, whichever is longer, prior to Screening.

Protocol Summary

To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of ravulizumab in pediatric patients (N≈18) with IgAN (cohort 1, n = 12) or IgAVN (cohort 2, n ≈ 6).

Study Locations

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