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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

17 Jun 2025 → ongoing

Decision date (initial)

2025-06-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic

To assess the efficacy of ravulizumab IV in pediatric participants

Secondary objectives 1

1. To characterize the PK and PD of treatment with ravulizumab IV in pediatric participants to support the extrapolation of efficacy from the adult population

Conditions and MedDRA coding

Immunoglobulin A Nephropathy

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001943-PIP07-24

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Participant must be ≥ 2 to < 18 years of age inclusive, at the time of signing the informed consent or assent.
2. The Investigator, or a person designated by the Investigator, will obtain written informed consent from each study participant’s legal guardian and the participant’s assent, when applicable, before any study-specific activity is performed. All legal guardians should be fully informed, and participants should be informed to the fullest extent possible, about the study in language and terms they are able to understand.
3. Legal guardian or primary caregiver must be able to accurately maintain the child’s take-home record, including items of general health.
4. Established diagnosis of primary IgAN diagnosis based on kidney biopsy with ≤ 50% interstitial fibrosis and tubular atrophy, and ≤ 50% glomerular sclerosis obtained within 3 years prior to Screening or during the Screening Period.
5. Established diagnosis of IgAVN based on kidney biopsy with ≤ 50% interstitial fibrosis and tubular atrophy, and ≤ 50% glomerular sclerosis obtained within 3 years prior to Screening or during the Screening Period.
6. If receiving immunosuppressive medications (eg, corticosteroid, cyclophosphamide, CNIs, mizoribine, or MMF) for the treatment of the renal manifestations of IgAVN, the medication must be stable for ≥ 1 month prior to Screening.
7. UPCR ≥ 1 g/g from the mean of 3 FMVs collected within 1 week during the Screening Period (should be collected at home).
8. eGFR ≥ 30 mL/min/1.73 m2 during Screening as calculated by the CKiD U25 (Cystatin C) equation (Pierce, 2021).
9. 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.
10. 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.
11. Body weight ≥ 10 kg at Screening.
12. Contraceptive and barrier use as well as pregnancy testing as appropriate for the age and sexual activity of pediatric participants and/or as required by local regulations as outlined in the protocol.
13. To reduce the risk of meningococcal infection (N meningitidis), all participants must be vaccinated against meningococcal infection from serogroups A, C, W135, and Y (and serogroup B, where available eg, United States, Europe, etc) within 3 years and at least 2 weeks prior to the first dose of study intervention. If vaccination occurs < 2 weeks from the first dose of study intervention, the participant will receive prophylactic antibiotics for at least 2 weeks after initial vaccination. Vaccinations must follow national/local guidelines.
14. Must have received vaccination against Haemophilus influenzae type b and Streptococcus pneumoniae unless previously vaccinated according to current national and local vaccination guidelines.
15. Male or female (according to their reproductive organs and functions assigned by chromosomal complement) (FDA, 2020) assigned at birth, inclusive of all gender identities.

Exclusion criteria 31

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. Drug or alcohol abuse or dependence within 1 year prior to Screening that interferes with ability to participate in the clinical study.
3. Secondary forms of IgAN not in the context of primary IgAN or IgAV (eg, due to systemic lupus erythematosus, cirrhosis, or celiac disease).
4. Concomitant clinically significant renal disease other than IgAN or IgAVN.
5. Clinical remission of IgAN/IgAVN or clinically significant improvement in proteinuria within the last 6 months.
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. 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.
12. Hemolytic uremic syndrome diagnosed any time prior to Screening.
13. Hypersensitivity to any ingredient contained in the study intervention, including murine proteins.
14. Received biologics for the treatment of IgAN or IgAVN within ≤ 6 months prior to Screening.
15. 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.
16. Received a complement inhibitor ≤ 30 days or 5 half-lives, whichever is longer, prior to Screening.
17. Current enrollment or past participation in any other clinical study in which an investigational intervention (eg, drug, vaccine, invasive device) was administered within 5 half-lives (if known) days before signing of consent in this clinical study.
18. Pregnant, breastfeeding, or intending to conceive during the study and within 8 months after the last dose of the study intervention.
19. Inability to travel to the clinic for specified visits during the study or fulfill the logistical requirements of study intervention administration.
20. Participant, parent, or legal guardian is involved in the planning and/or conduct of the study (applies to both Sponsor personnel and/or site personnel).
21. Received systemic immunosuppression (eg, corticosteroid, cyclophosphamide, CNIs, mizoribine, or MMF),) within 3 months prior to Screening or budesonide within 6 months prior to Screening for the treatment of IgAN.
22. Received systemic immunosuppression within 3 months prior to Screening for extrarenal manifestations of IgAV.
23. Planned urological surgery expected to influence kidney function within the study time frame.
24. History of severe IgAV symptoms (eg, including but not limited to orchitis, cerebral vasculitis, pulmonary hemorrhage, gastrointestinal bleeding) within 1 year before Screening.
25. Congenital immunodeficiency.
26. History of unexplained, recurrent infection.
27. 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.
28. History of or unresolved N meningitidis infection.
29. Known history of HIV, active hepatitis B infection, or active hepatitis C infection.
30. Active systemic bacterial, viral, or fungal infection within 14 days prior to enrollment.
31. Uncontrolled diabetes mellitus with HbA1c > 8.5%.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline in proteinuria based on UPCR at Week 34.

Secondary endpoints 4

1. 1. PK/PD parameters (at trough and peak) will be evaluated at Baseline and at different timepoints through Week 34 as follows: • PK: Cmax and Ctrough (measured at end of dosing interval) • PD: change in serum free C5 concentrations over time • Change from Baseline in proteinuria based on UPCR at Week 10
2. Incidence of TEAEs, TESAEs, and AESIs over time.
3. Change from Baseline in vital signs, and laboratory assessments.
4. ADA incidence, ADA response categories, and titer, as well as NAb incidence for the duration of the study.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications