A Study of an Investigational Drug, Cemdisiran (ALN-CC5), in Patients With Atypical Hemolytic Uremic Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of Cemdisiran in patients with aHUS.

Official Title
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A Phase 2, Open Label, Multicenter Study of ALN-CC5 Administered Subcutaneously in Adult Patients With Atypical Hemolytic Uremic Syndrome

Conditions
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Atypical Hemolytic Uremic Syndrome

Intervention / Treatment
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* Drug: Cemdisiran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to provide written informed consent and to comply with the study requirements Age 18 years or older Clinical diagnosis of primary aHUS Clinical thrombotic microangiopathy (TMA) activity 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 Previously vaccinated with meningococcal group ACWY conjugate vaccine and meningococcal group B vaccine or willingness to receive these vaccinations ADAMTS13 >10% or other proven aHUS-associated mutation Exclusion Criteria: Clinically significant abnormal laboratory results Positive Shiga toxin producing Escherichia coli test at Screening Suspected secondary aHUS, in the opinion of the Investigator (unless there is a documented aHUS-associated genetic mutation) Positive direct Coombs test Patients who have received hemodialysis for >3 months Bone marrow transplant recipients Organ transplant recipients, except for kidney transplant recipients with primary aHUS (confirmed by known genetic mutation and kidney biopsy) Known history or evidence of systemic lupus erythematosus or antiphospholipid antibody syndrome History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc 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 Patients with a poor prognosis that is expected to limit their life expectancy to less than 3 months, in the opinion of the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cemdisiran<br> | Drug: Cemdisiran<br>* Subcutaneous (sc) injection of Cemdisiran<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of Cemdisiran on platelet count |  | Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of Cemdisiran on hematological response as measured by platelet count |  | after 32 weeks of treatment | 
| 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 complete Thrombotic microangiopathy (TMA) response as measured by LDH |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemolysis, aHUS, RNAi therapeutic, Atypical Hemolytic Uremic Syndrome, Thrombocytopenia, Renal insufficiency, Thrombotic Microangiopathy, TMA