Phase 3
N=34
Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical Hemolytic Uremic Syndrome (aHUS)
Bottom Line
View on ClinicalTrials.gov: NCT03131219 ↗Enrolled (actual)
34
Serious AEs
50.0%
Results posted
Sep 2020
Primary outcome: 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 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Ravulizumab (Biological)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Primary completion
- Dec 2022
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 | — |
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.
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). 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.