ALXN1210 IN CHILDREN AND ADOLESCENTS WITH aHUS.
Research type
Research Study
Full title
A PHASE 3, OPEN-LABEL, MULTICENTER STUDY OF ALXN1210 IN CHILDREN AND ADOLESCENTS WITH ATYPICAL HEMOLYTIC-UREMIC SYNDROME (aHUS)
IRAS ID
224376
Contact name
Sally Ann Johnson
Contact email
Sponsor organisation
Alexion Pharmaceuticals Inc
Eudract number
2016-002499-29
Clinicaltrials.gov Identifier
128367, IND number
Duration of Study in the UK
3 years, 6 months, 1 days
Research summary
Research Summary- The purpose of this study is to determine the ability of a new drug, ALXN1210, to treat the disease atypical Hemolytic Uremic Syndrome (aHUS) in children and adolescents. aHUS is a rare, life-threatening, genetic disease that can damage vital organs such as the kidneys, heart and brain. A drug similar to ALXN1210, called eculizumab (brand name Soliris), is currently the standard of care for aHUS patients.
ALXN1210 is being developed for the treatment of disorders involving the complement system, a branch of the body’s immune system that fights against infection. In aHUS, the complement system is not controlled properly and this can result in damage to the blood vessels, known as thrombotic microangiopathy (TMA). In TMA, platelets (which are required for normal blood clotting) become overactive and form clots in blood vessels throughout the body. These clots can block blood flow, create inflammation, and travel to other organs, causing further damage.
ALXN1210 is classified as an immunosuppressant drug as it works by suppressing the activity of a specific portion of the complement system. aHUS is an example of a complement disease that could be eventually treated with ALXN1210. Patients with aHUS who have not had any previous treatment with a complement inhibitor are eligible.
The dose of ALXN1210 received by patients will be based on body weight. ALXN1210 will be administered intravenously into a vein and blood samples will be collected throughout the study for various analyses.
There are 3 periods in this study: Screening (up to 7 days), a 26-week Initial Evaluation Period and an Extension Period (up to 2 years). The duration of participation in the study is estimated to be approximately 2 and a half years. It is expected that approximately 60 centres will be opened around the world in order to enrol between 16 and 24 participants.
Summary of results- The analysis of final data for the 24 patients enrolled in Cohort 1 demonstrated that ravulizumab provided immediate, complete, and sustained inhibition of terminal complement in this complement inhibitor treatment naïve pediatric Atypical Hemolytic Uremic Syndrome (aHUS) population.
Complete mediated thrombotic microangiopathy (TMA) Response was achieved in 90.0% of patients, with consistent results observed for individual response components as well as other secondary efficacy endpoints of chronic kidney disease (CKD) stage and dialysis requirement.
After the Initial Evaluation Period, patients continued to benefit from ravulizumab treatment during the Extension Period and through the remainder of the study. Improvements in all hematologic TMA parameters (platelets, lactate dehydrogenase, and hemoglobin) during the Initial Evaluation Period were maintained with extended ravulizumab treatment.
Decreased disease burden was also evident based on the reduced need for dialysis, as no patients were reported to re-initiate dialysis after starting treatment with ravulizumab, and improved quality of life (QoL) scores.
Data for the 10 patients enrolled in Cohort 2 show that switching patients from eculizumab to ravulizumab results in complete and sustained inhibition of terminal complement. The efficacy results demonstrate maintenance of TMA parameters and kidney function as well as additional benefits in QoL. Following body weight-based dosing with ravulizumab, immediate and complete terminal complement inhibition was achieved and sustained throughout the treatment period for complement inhibitor naïve and eculizumab experienced pediatric patients. No treatment emergent immunogenicity responses were observed in either complement inhibitor naïve or eculizumab experienced pediatric patients. Ravulizumab was well tolerated in both complement inhibitor treatment naïve pediatric patients and eculizumab experienced pediatric patients, with no unexpected safety concerns. The data in this final analysis support the favorable benefit/risk profile of ravulizumab and its use for the treatment of pediatric patients with aHUS regardless of experience with prior complement inhibitor treatment.REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
17/EM/0122
Date of REC Opinion
18 May 2017
REC opinion
Further Information Favourable Opinion