Clinical trial NCT03303313: A Study of an Investigational Drug, Cemdisiran (ALN-CC5), in Patients With Atypical Hemolytic Uremic Syndrome
Official title: A Phase 2, Open Label, Multicenter Study of ALN-CC5 Administered Subcutaneously in Adult Patients With Atypical Hemolytic Uremic Syndrome
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Atypical Hemolytic Uremic Syndrome
Keywords: RNAi therapeutic
Atypical Hemolytic Uremic Syndrome
Hemolysis
Thrombocytopenia
Renal insufficiency
Thrombotic Microangiopathy
aHUS
TMA
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-10-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: The effect of Cemdisiran on platelet count
timeFrame: Week 32
Secondary outcomes:
measure: The effect of Cemdisiran on hematological response as measured by platelet count
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on hematological response as measured by lactate dehydrogenase (LDH)
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on hematological response as measured by rescue plasma therapy
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on LDH response as measured by LDH
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on LDH response as measured by rescue plasma therapy
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on complete Thrombotic microangiopathy (TMA) response as measured by platelet count
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on complete Thrombotic microangiopathy (TMA) response as measured by LDH
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on complete Thrombotic microangiopathy (TMA) response as measured by serum creatinine levels
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on complete Thrombotic microangiopathy (TMA) response as measured by rescue plasma therapy
timeFrame: after 32 weeks of treatment
measure: The effect of Cemdisiran on serum creatinine levels
timeFrame: up to 84 weeks
measure: The effect of Cemdisiran on estimated glomerular filtration rate (eGFR)
timeFrame: up to 84 weeks
measure: The effect of Cemdisiran on adverse events (AEs)
timeFrame: up to 108 weeks
Other outcomes:
Locations:
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Trial Site
city: Calgary
country: Canada
facility: Clinical Trial Site
city: Tallinn
country: Estonia
facility: Clinical Trial Site
city: Tartu
country: Estonia
facility: Clinical Trial Site
city: Tbilisi
country: Georgia
facility: Clinical Trial Site
city: Riga
country: Latvia
facility: Clinical Trial Site
city: Kaunas
country: Lithuania
facility: Clinical Trial Site
city: Vilnius
country: Lithuania
facility: Clinical Trial Site
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Clinical Trial Site
city: Chisinau
country: Moldova, Republic of
facility: Clinical Trial Site
city: Belgrade
country: Serbia
facility: Clinical Trial Site
city: Örebro
country: Sweden
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Nader Najafian, MD
role: STUDY_DIRECTOR
References: