aHUS, Atypical Hemolytic Uremic Syndrome
Conditions
Keywords
aHUS, atypical hemolytic uremic syndrome, ravulizumab
Brief summary
The primary objective of this study is to assess the platelet count response to ravulizumab in participants clinically diagnosed as atypical hemolytic uremic syndrome (aHUS).
Interventions
DRUGRavulizumab
Participants will receive ravulizumab via IV infusion.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body weight ≥20 kilograms (kg) * Participants clinically diagnosed as aHUS who have any of diseases/conditions listed below (including participants in whom Thrombotic microangiopathy (TMA) has not been improved even after treatment for the pathogenesis of diagnosed secondary TMA and therefore, diagnosis of aHUS was made). * Infection (except for pneumococcal infection and Siga toxin-producing Escherichia coli infection) * During pregnancy or postpartum * Post-renal transplantation * Hypertensive crisis/malignant hypertension * Systemic lupus erythematosus and related diseases (e.g. dermatomyositis, mixed connective tissue disease, etc.) * Participants with the following three signs: * Thrombocytopenia: Platelet count \<150,000/microliter (μL) * Microangiopathic haemolytic anaemia: Hb \< 10 grams per deciliter (g/dL) (\*) * Acute kidney injury: one of the following is fulfilled; 1. ΔsCr ≥ 0.3 milligrams per deciliter (mg/dL) (within 48 hours), 2. 1.5-fold increase from baseline sCr (within 7 days), 3. urinary output ≤ 0.5 mL/kg/hour for ≥ 6 hours. * No prior treatment with complement inhibitors. * The investigator plans to provide the participant with 26-week treatment with ravulizumab in accordance with the treatment policy in clinical practice. * Ravulizumab treatment is planned to be initiated within 14 days after onset of the latest TMA episode. * Participants consenting to meningococcal vaccine administration and appropriate antibiotic prophylaxis (if required).
Exclusion criteria
* Participants with TTP, STEC-HUS, secondary TMA that is obviously unrelated to complement abnormality. * Participants with TMA caused by malignant tumors, abnormal Cobalamin C metabolism, Streptococcus pneumoniae, drugs, autoimmune diseases other than systemic lupus erythematosus and related diseases (e.g. scleroderma etc.), or hematopoietic stem cell transplantation * Participants with pathological complement gene variants (CFH, CFI , CD46 (MCP), C3, CFB, THBD, DGKE) associated with the development of aHUS at enrolment * Participants with positive anti-factor H antibodies * More than 14 day from onset of TMA to the planned start of ravulizumab treatment * Chronic kidney disease or irreversible renal impairment that requires chronic dialysis * Presence of unresolved meningococcal disease * Judgement by the investigator that the participant is not eligible for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Showing Improvement in Platelet Count During the 26-week Ravulizumab Treatment | Baseline up to Week 26 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants Showing Improvement in Renal Function During the 26-week Ravulizumab Treatment | Baseline up to Week 26 |
| Percentage of Participants Showing Improvement in Platelet Count | Day 4 and on Weeks 1, 2, 10, 18, and 26 |
| Percentage of Participants Showing Improvement in Renal Function | Day 4 and on Weeks 1, 2, 10, 18, and 26 |
| Percentage of Participants Showing Improvement in Complete Thrombotic Microangiopathy (TMA) Response or Partial TMA Response | Day 4 and on Weeks 1, 2, 10, 18, and 26 |
| Percentage of Participants who are on Dialysis on Day 1 and are Able to Withdraw From Dialysis by Week 26 | Baseline (Day 1) up to Week 26 |
| Change from Baseline in Platelet Count | Baseline (Day 1), Week 26 |
| Change From Baseline in Hemoglobin | Baseline (Day 1), Week 26 |
| Change From Baseline in Lactate Dehydrogenase | Baseline (Day 1), Week 26 |
| Change From Baseline in Estimated Glomerular Filtration Rate | Baseline (Day 1), Week 26 |
Countries
Japan
Contacts
CONTACTAlexion Pharmaceuticals, Inc. (Sponsor)
Outcome results
None listed