Loading clinical trials...

Eculizumab to Cemdisiran Switch in aHUS | Clinical Trials | Clareo Health

WITHDRAWNPHASE2

Eculizumab to Cemdisiran Switch in aHUS

A Phase II, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Cemdisiran (ALN-CC5) Following Withdrawal of Chronic Eculizumab Therapy in Patients With Atypical HUS at High Risk of Recurrence

NCT03999840•Mario Negri Institute for Pharmacological Research

View on ClinicalTrials.gov

Summary

Atypical Hemolytic Uremic Syndrome (aHUS) is a rare, lifethreatening, chronic disease of complement-mediated thrombotic microangiopathy (TMA) characterized by acute onset of renal impairment, thrombocytopenia, and microangiopathic hemolytic anemia. The estimated incidence of aHUS is approximately 0.5 per million per year. aHUS affects both adults and children, but is observed primarily in children and young adults. Atypical HUS commonly develops due to dysregulation of the alternative complement pathway and can be sporadic (80%) or familial(20%). The clinical course of aHUS is often unpredictable and can be dependent upon the specific genetic abnormality present within the complement system, if any, and/or triggering events associated with complement activation or inflammation, including autoimmune disease, transplant, pregnancy, infection, metabolic conditions, and drug use. In patients with dysregulated complement activity, such as those with complement mutations commonly observed in aHUS, the kidney vasculature is often the site of thrombosis stemming from endothelial injury. Cemdisiran has been designed to reduce the level of C5 mRNA in the liver, thereby reducing levels of circulating C5 protein, inhibiting terminal complement pathway activity, and preventing formation and deposition of the MAC (C5-b9) on endothelial cells in the kidney. As a result, complement-mediated endothelial cell damage in patients with aHUS and subsequent progression to End Stage Renal Disease (ESRD) may be reduced.

Eligibility

Age

12 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. 12 years and older at the time of consent;
•2. Written informed consent (of parents or the guardian in case of underage participants) to enter the study;
•3. Consent to stop eculizumab therapy during the whole study period and to resume eculizumab therapy in case of disease recurrence
•4. \>40 kg body weight;
•5. On stable disease status with eculizumab continuous therapy for aHUS for ≥ 12 consecutive months (stability assessed on the basis of hematological/biochemical parameters by the Investigator)
•6. Hematological remission at screening and inclusion;
•7. Estimated GFR (by the simplified MDRD equation) \> 30/ml/min 1.73 m2;
•8. Known high risk of aHUS recurrence due to at least one of the following criteria;
•1. History of aHUS recurrence after interruption of eculizumab therapy;
•2. Plasma dependent and/or recurrent disease before the introduction of eculizumab therapy;
+3 more criteria

Exclusion Criteria

•1. Solid organ or bone marrow/stem cell transplantation;
•2. Alanine transaminase (ALT) \>3×ULN, INR \>2 (or \>3.5 if on anticoagulants), or total bilirubin \>3×ULN (unless bilirubin elevation is due to Gilbert's syndrome);
•3. Clinical or biochemical evidence of active thrombotic; microangiopathy or flare of aHUS at the time of enrolment
•4. Evidence of Shigatoxin associated HUS;
•5. Patients who required intensified eculizumab therapy because of uncontrolled disease (these patients could be at very high risk of relapse after the shift, even in the cemdisiran treatment arm and their inclusion could be unsafe);
•6. Patients who did not relapse despite prolonged (\>3 months) interruption of eculizumab therapy (these would probably be low risk patients that are expected to be event-free throughout the whole study period independent of treatment allocation and could have a dilution effect for event analyses);
•7. Patients with a confirmed diagnosis of sepsis, defined as positive blood cultures within 7 days of the screening visit and not treated with antibiotics to which the organism is sensitive;
•8. Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease;
•9. Evidence of human immunodeficiency virus (HIV) (positive serology for HIV antibody \[HIV Ab\]), hepatitis B infection (positive hepatitis B surface antigen \[HbsAg\]), or hepatitis C infection (positive anti-HCV antibody \[HCV Ab\]) at Screening or historically
•10. Unresolved meningococcal disease;
+14 more criteria

Locations (1)

Centro di Ricerche Cliniche per le Malattie Rare " Aldo e Cele Daccò"

Ranica, BG, Italy

Key Dates

Start Date

January 1, 2021

Primary Completion Date

January 1, 2024

Completion Date

March 1, 2024

Last Updated

March 10, 2021

Conditions

Atypical Hemolytic Uremic Syndrome

Interventions

cemdisiran

DRUG

Placebos

DRUG

Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy

NCT05805202

Atypical Hemolytic Uremic Syndrome

View study

RECRUITING

National Registry of Rare Kidney Diseases

NCT06065852

Adenine Phosphoribosyltransferase DeficiencyAH Amyloidosis+82 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 10, 2021Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Eculizumab to Cemdisiran Switch in aHUS

Inclusion Criteria

Exclusion Criteria

Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy

National Registry of Rare Kidney Diseases

Study of NM8074 in Patients with AHUS with Evidence of Ongoing Thrombotic Microangiopathy

Eculizumab Use in the Postpartum Period for the Treatment of Pregnancy Associated aHUS: A Case Series

Complement Inhibition in aHUS Dialysis Patients

The Safety and Efficacy of Eculizumab in Japanese Patients With Atypical Hemolytic Uremic Syndrome (aHUS)