Phase 3
Completed N=34
Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical Hemolytic Uremic Syndrome (aHUS)
Source: ClinicalTrials.gov NCT03131219 ↗
Enrolled (actual)
34
Serious AEs
50.0%
Results posted
Sep 2020
Primary outcomePrimary: Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 — 77.8; 94.4; 88.9; 83.3 percentage of participants
◆ Published Evidence
Highly cited
219citations · ~37 / year
The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment.
Summary
The purpose of the study is to assess the efficacy of ravulizumab to control disease activity in children and adolescents with aHUS who have not previously used a complement inhibitor (complement inhibitor treatment-naïve), as well as in complement inhibitor-experienced (eculizumab-experienced) adolescent participants.
Linked Publications (4)
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The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment.
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The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab.
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Interventions for atypical haemolytic uraemic syndrome.
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Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 |
77.8; 94.4; 88.9; 83.3 | — |
| SECONDARY Time To Complete TMA Response In Complement Inhibitor Treatment-naïve Participants |
30.0 | — |
| SECONDARY Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52 |
0.882; 0.882; 1.000; 1.000 | — |
| SECONDARY Participants Who Do Not Require Dialysis at Weeks 26 and 52 |
5; 0; 6; 0 | — |
| SECONDARY Change From Baseline In eGFR At Weeks 26 and 52 |
22.0; 99.75; 80.0; -2.00; 94.0; -3.00 | — |
| SECONDARY Participants With Change From Baseline In CKD Stage At Weeks 26 and 52 |
15; 0; 0; 3; 2; 7 | — |
| SECONDARY Change From Baseline In Platelet Count At Weeks 26 and 52 |
51.25; 281.75; 247.00; -2.25; 213.00; -34.75 | — |
| SECONDARY Change From Baseline In LDH At Weeks 26 and 52 |
1963.00; 206.50; -1851.50; -8.50; -1825.50; -17.50 | — |
| SECONDARY Change From Baseline In Hemoglobin At Weeks 26 and 52 |
74.25; 132.00; 46.50; -3.50; 51.50; 5.50 | — |
| SECONDARY Percentage Of Complement Inhibitor Treatment-naïve Participants With An Increase From Baseline In Hemoglobin ≥20 g/L Through Week 26 and Week 52 |
100; 94.1 | — |
| SECONDARY Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire (Participants ≥5 Years Of Age) At Weeks 26 and 52 |
35.00; 50.00; 10.00; 0.00; 9.00; -1.00 | — |
Eligibility Criteria
Inclusion Criteria
Complement Inhibitor Treatment Naïve:
- Participants from birth up to <18 years of age and weighing ≥5 kilograms (kg) at the time of consent.
- Participants had not been previously treated with complement inhibitors.
- Evidence of thrombotic microangiopathy (TMA), including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
- Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
- Female participants of childbearing potential and male participants with female partners of childbearing potential must have used highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
Eculizumab Experienced:
- Participants between 12 and <18 years of age (non-Japanese sites) or <18 years of age (Japanese sites) who had been treated with eculizumab according to the labelled dosing recommendation for aHUS for at least 90 days prior to screening.
- Participants with documented diagnosis of aHUS.
- Participants with clinical evidence of response to eculizumab indicated by stable TMA parameters at screening.
- Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
- Females of childbearing potential and male participants with female partners of childbearing potential must have used highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
Exclusion Criteria
- Known familial or acquired ADAMTS13 ("a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13") deficiency (activity <5%).
- Known Shiga toxin-related hemolytic uremic syndrome.
- Positive direct Coombs test.
- Females who planned to become pregnant during the study or were currently pregnancy or breastfeeding.
- Identified drug exposure-related hemolytic uremic syndrome.
- Bone marrow transplant/hematopoietic stem cell transplant within the last 6 months prior to the start of screening.
- Hemolytic uremic syndrome related to known genetic defects of cobalamin C metabolism.
- Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome.
- Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease.
- For eculizumab-experienced participants, prior use of complement inhibitors other than eculizumab.
- For eculizumab-experienced participants, any known abnormal TMA parameters within 90 days prior to screening.
Data sourced from ClinicalTrials.gov (NCT03131219) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.