Atypical Hemolytic Uremic Syndrome
Conditions
Keywords
RNAi therapeutic, Atypical Hemolytic Uremic Syndrome, Hemolysis, Thrombocytopenia, Renal insufficiency, Thrombotic Microangiopathy, aHUS, TMA
Brief summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of Cemdisiran in patients with aHUS.
Interventions
DRUGCemdisiran
Subcutaneous (sc) injection of Cemdisiran
Sponsors
Alnylam Pharmaceuticals
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
1. Willing to provide written informed consent and to comply with the study requirements 2. Age 18 years or older 3. Clinical diagnosis of primary aHUS 4. Clinical thrombotic microangiopathy (TMA) activity 5. Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception 6. Previously vaccinated with meningococcal group ACWY conjugate vaccine and meningococcal group B vaccine or willingness to receive these vaccinations 7. ADAMTS13 \>10% or other proven aHUS-associated mutation
Exclusion criteria
1. Clinically significant abnormal laboratory results 2. Positive Shiga toxin producing Escherichia coli test at Screening 3. Suspected secondary aHUS, in the opinion of the Investigator (unless there is a documented aHUS-associated genetic mutation) 4. Positive direct Coombs test 5. Patients who have received hemodialysis for \>3 months 6. Bone marrow transplant recipients 7. Organ transplant recipients, except for kidney transplant recipients with primary aHUS (confirmed by known genetic mutation and kidney biopsy) 8. Known history or evidence of systemic lupus erythematosus or antiphospholipid antibody syndrome 9. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc 10. Malignancy (except for non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years 11. Patients with a poor prognosis that is expected to limit their life expectancy to less than 3 months, in the opinion of the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The effect of Cemdisiran on platelet count | Week 32 |
Secondary
| Measure | Time frame |
|---|---|
| The effect of Cemdisiran on hematological response as measured by lactate dehydrogenase (LDH) | after 32 weeks of treatment |
| The effect of Cemdisiran on hematological response as measured by rescue plasma therapy | after 32 weeks of treatment |
| The effect of Cemdisiran on LDH response as measured by LDH | after 32 weeks of treatment |
| The effect of Cemdisiran on LDH response as measured by rescue plasma therapy | after 32 weeks of treatment |
| The effect of Cemdisiran on complete Thrombotic microangiopathy (TMA) response as measured by platelet count | after 32 weeks of treatment |
| The effect of Cemdisiran on hematological response as measured by platelet count | after 32 weeks of treatment |
| The effect of Cemdisiran on complete Thrombotic microangiopathy (TMA) response as measured by serum creatinine levels | after 32 weeks of treatment |
| The effect of Cemdisiran on complete Thrombotic microangiopathy (TMA) response as measured by rescue plasma therapy | after 32 weeks of treatment |
| The effect of Cemdisiran on serum creatinine levels | up to 84 weeks |
| The effect of Cemdisiran on estimated glomerular filtration rate (eGFR) | up to 84 weeks |
| The effect of Cemdisiran on adverse events (AEs) | up to 108 weeks |
| The effect of Cemdisiran on complete Thrombotic microangiopathy (TMA) response as measured by LDH | after 32 weeks of treatment |
Countries
Bosnia and Herzegovina, Canada, Estonia, Georgia, Latvia, Lithuania, Moldova, North Macedonia, Serbia, Sweden
Outcome results
None listed