Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-naïve Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
2 other identifiers
interventional
58
13 countries
36
Brief Summary
The purpose of the study is to assess the safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement inhibitor.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jan 2017
Longer than P75 for phase_3
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 25, 2016
CompletedFirst Posted
Study publicly available on registry
October 31, 2016
CompletedStudy Start
First participant enrolled
January 11, 2017
CompletedResults Posted
Study results publicly available
February 10, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 24, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 24, 2023
CompletedFebruary 20, 2024
January 1, 2024
6 years
October 25, 2016
December 11, 2019
January 24, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage Of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
Complete TMA response during the 26-week Initial Evaluation Period is a composite outcome measure that required normalization of hematological parameters (platelet count and lactate dehydrogenase \[LDH\]) and improvement in kidney function (≥25% reduction in serum creatinine from baseline); for participants on dialysis, baseline was established at least 6 days after the end of dialysis. Participants had to meet these criteria for 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. To be considered a responder during the 26-week Initial Evaluation Period, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment. Formal statistical comparison analyses were not planned for this study. The percentage was based on the responders among treated participants. The 95% confidence interval (CI) was based on the asymptotic Gaussian approximation method with a continuity correction.
Week 26
Secondary Outcomes (11)
Time To Complete TMA Response
Baseline through Week 114
Participants Who Do Not Require Dialysis at Weeks 26 and 52
Week 26 and Week 52
Proportion Of Participants With Complete TMA Response At Week 52
Week 52
Change From Baseline In Estimated Glomerular Filtration Rate (eGFR) At Weeks 26 and 52
Baseline, Week 26 and Week 52
Participants With Change From Baseline In CKD Stage At Weeks 26 and 52
Baseline, Week 26, and Week 52
- +6 more secondary outcomes
Study Arms (1)
Ravulizumab
EXPERIMENTALParticipants were administered weight-based doses of ravulizumab every 8 weeks for 26 weeks in the Initial Evaluation Period. After the Initial Evaluation Period, participants could enter an Extension Period and receive ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.
Interventions
Single loading dose on Day 1, followed by regular maintenance dosing beginning on Day 15, based on weight: ≥ 40 to \< 60 kilograms (kg), 2400 milligrams (mg) loading, then 3000 mg every 8 weeks; ≥ 60 to \< 100 kg, 2700 mg loading, then 3300 mg every 8 weeks; ≥ 100 kg, 3000 mg loading, then 3600 mg every 8 weeks.
Eligibility Criteria
You may qualify if:
- Male or female ≥ 12 years of age and weighing ≥ 40 kg at the time of consent.
- Evidence of thrombotic microangiopathy, including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
- Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study drug. Participants who received a meningococcal vaccine less than 2 weeks before initiating ravulizumab treatment must have received treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Participants who had not been vaccinated prior to initiating ravulizumab treatment should have received prophylactic antibiotics prior to and for at least 2 weeks after meningococcal vaccination. Participants \< 18 years of age must have been vaccinated against haemophilus influenzae type b and streptococcus pneumoniae according to national and local vaccination schedule guidelines.
- Female participants of childbearing potential and male participants with female partners of childbearing potential had to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
You may not qualify if:
- A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency (activity \< 5%).
- Shiga toxin-related hemolytic uremic syndrome.
- Positive direct Coombs test.
- Pregnancy or breastfeeding.
- Identified drug exposure-related hemolytic uremic syndrome (HUS).
- Bone marrow transplant/hematopoietic stem cell transplant within last 6 months prior to start of Screening.
- HUS related to known genetic defects of cobalamin C metabolism.
- Systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome.
- Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (37)
Clinical Trial Site
Fort Wayne, Indiana, 46804, United States
Clinical Trial Site
Fort Wayne, Indiana, 46845, United States
Clinical Trial Site
Durham, North Carolina, 27705, United States
Clinical Trial Site
Winston-Salem, North Carolina, 27103, United States
Clinical Trial Site
Columbus, Ohio, 43210, United States
Clinical Trial Site
Clayton, Australia
Clinical Trial Site
Geelong, Australia
Clinical Trial Site
Parkville, Australia
Clinical Trial Site
Vienna, Austria
Clinical Trial Site
Brussels, Belgium
Clinical Trial Site
London, Canada
Clinical Trial Site
Bordeaux, France
Clinical Trial Site
Clermont-Ferrand, France
Clinical Trial Site
Lille, France
Clinical Trial Site
Montpellier, France
Clinical Trial Site
Nice, France
Clinical Trial Site
Paris, France
Clinical Trial Site
Aachen, Germany
Clinical Trial Site
Essen, Germany
Clinical Trial Site
Hanover, Germany
Clinical Trial Site
München, Germany
Clinical Trial Site
Tübingen, Germany
Clinical Trial Site
Bologna, Italy
Clinical Trial Site
Florence, Italy
Clinical Trial Site
Saitama, Japan
Clinical Trial Site
Tokyo, Japan
Clinical Trial Site
Moscow, Russia
Clinical Trial Site
Saint Petersburg, Russia
Clinical Trial Site
Gyeonggi-do, South Korea
Clinical Trial Site
Seoul, South Korea
Clinical Trial Site
Barcelona, Spain
Clinical Trial Site
Madrid, Spain
Clinical Trial Site
Valencia, Spain
Clinical Trial Site
Taichung, Taiwan
Clinical Trial Site
Taipei, Taiwan
Clinical Trial Site
Cardiff, United Kingdom
Clinical Trial Site
London, United Kingdom
Related Publications (5)
Barbour T, Scully M, Ariceta G, Cataland S, Garlo K, Heyne N, Luque Y, Menne J, Miyakawa Y, Yoon SS, Kavanagh D; 311 Study Group Members. Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults. Kidney Int Rep. 2021 Mar 24;6(6):1603-1613. doi: 10.1016/j.ekir.2021.03.884. eCollection 2021 Jun.
PMID: 34169200RESULTMatsumoto M, Shimono A, Yokosawa J, Hirose K, Wang E, Maruyama S. Correlation between a 2-week change in platelet count and clinical outcomes after the initiation of ravulizumab treatment in adult patients with atypical hemolytic uremic syndrome: post-hoc analysis of the phase III trial. Thromb J. 2024 Oct 28;22(1):93. doi: 10.1186/s12959-024-00652-1.
PMID: 39468592DERIVEDCammett TJ, Garlo K, Millman EE, Rice K, Toste CM, Faas SJ. Exploratory Prognostic Biomarkers of Complement-Mediated Thrombotic Microangiopathy (CM-TMA) in Adults with Atypical Hemolytic Uremic Syndrome (aHUS): Analysis of a Phase III Study of Ravulizumab. Mol Diagn Ther. 2023 Jan;27(1):61-74. doi: 10.1007/s40291-022-00620-3. Epub 2022 Nov 4.
PMID: 36329366DERIVEDPugh D, O'Sullivan ED, Duthie FA, Masson P, Kavanagh D. Interventions for atypical haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Mar 23;3(3):CD012862. doi: 10.1002/14651858.CD012862.pub2.
PMID: 33783815DERIVEDGackler A, Schonermarck U, Dobronravov V, La Manna G, Denker A, Liu P, Vinogradova M, Yoon SS, Praga M. Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis. BMC Nephrol. 2021 Jan 6;22(1):5. doi: 10.1186/s12882-020-02190-0.
PMID: 33407224DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Alexion Pharmaceuticals Inc.
- Organization
- Alexion Pharmaceuticals Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 25, 2016
First Posted
October 31, 2016
Study Start
January 11, 2017
Primary Completion
January 24, 2023
Study Completion
January 24, 2023
Last Updated
February 20, 2024
Results First Posted
February 10, 2020
Record last verified: 2024-01