Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger

September 16, 2024 updated by: Alexion Pharmaceuticals, Inc.

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants Who Have Thrombotic Microangiopathy Associated With a Trigger

This study will investigate the efficacy and safety of ravulizumab compared to placebo in adult participants with thrombotic microangiopathy (TMA) associated with a trigger. Participants will be randomized to receive either ravulizumab plus best supportive care or placebo plus best supportive care. The treatment period is 26 weeks followed by a 26-week off-treatment follow-up period.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Belgium, Belgium, 1200
        • Research Site
      • Brussels, Belgium, 1070
        • Research Site
      • Edegem, Belgium, 2650
        • Research Site
      • Leuven, Belgium, 3000
        • Research Site
      • Liege, Belgium, 4000
        • Research Site
  • Brazil
      • Belo Horizonte, Brazil, 30150-221
        • Research Site
      • Botucatu, Brazil, 18618-687
        • Research Site
      • Campinas, Brazil, 13083-894
        • Research Site
      • Fortaleza, Brazil, 60430-375
        • Research Site
      • Porto Alegre, Brazil, 90110-270
        • Research Site
      • Ribeirão Preto, Brazil, 14051-040
        • Research Site
      • Salvador, Brazil, 41253-190
        • Research Site
      • Sao Paulo, Brazil, 05403-000
        • Research Site
      • São Paulo, Brazil, 04036-002
        • Research Site
  • Canada
      • Quebec, Canada, G1R 3S1
        • Research Site
    • Ontario
      • Kingston, Ontario, Canada, K7L 3N6
        • Research Site
      • Toronto, Ontario, Canada, M5B 1W8
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H2X 3E4
        • Research Site
  • France
      • Bordeaux, France, 33076
        • Research Site
      • Chambéry Cedex, France, 73011
        • Research Site
      • Lille, France, 59037
        • Research Site
      • Montpellier, France
        • Research Site
      • PARIS Cedex 12, France, 75571
        • Research Site
      • Paris, France, 75020
        • Research Site
      • Tours Cedex 09, France, 37044
        • Research Site
  • Germany
      • Essen, Germany, 45147
        • Research Site
      • Hannover, Germany, 30625
        • Research Site
  • Italy
      • Bergamo, Italy, 24127
        • Research Site
      • Roma, Italy, 00168
        • Research Site
  • Japan
      • Bunkyo-ku, Japan, 113-8431
        • Research Site
      • Iruma-Gun, Japan, 350-0495
        • Research Site
      • Mitaka-shi, Japan, 181-8611
        • Research Site
      • Miyazaki-shi, Japan, 889-1692
        • Research Site
      • Nagoya, Japan, 466-8650
        • Research Site
      • Nagoya-shi, Japan, 466-8560
        • Research Site
      • Osaka, Japan, 565-0871
        • Research Site
      • Sapporo-shi, Japan, 060-8648
        • Research Site
      • Sendai-shi, Japan, 980-8574
        • Research Site
      • Shinjuku-ku, Japan, 162-8666
        • Research Site
  • Korea, Republic of
      • Daegu, Korea, Republic of, 42415
        • Research Site
      • Gwangju, Korea, Republic of, 61469
        • Research Site
      • Seoul, Korea, Republic of, 03080
        • Research Site
      • Seoul, Korea, Republic of, 02841
        • Research Site
      • Seoul, Korea, Republic of, 04401
        • Research Site
      • Seoul, Korea, Republic of, 6591
        • Research Site
      • Seoul, Korea, Republic of, 06973
        • Research Site
      • Seoul, Korea, Republic of, 134-727
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands, 1100 DD
        • Research Site
      • Groningen, Netherlands, 9713 GZ
        • Research Site
      • Maastricht, Netherlands, 6229 HX
        • Research Site
      • Nijmegen, Netherlands, 6500 HB
        • Research Site
  • Spain
      • Barcelona, Spain, 08036
        • Research Site
      • Granada, Spain, 18014
        • Research Site
      • Las Palmas de Gran Canaria, Spain, 35016
        • Research Site
      • Madrid, Spain, 28040
        • Research Site
  • Taiwan
      • Kaohsiung, Taiwan, 81362
        • Research Site
      • Kaohsiung City, Taiwan, 833401
        • Research Site
      • New Taipei, Taiwan, 23561
        • Research Site
      • Taichung, Taiwan, 40705
        • Research Site
      • Taichung, Taiwan, 40447
        • Research Site
      • Taipei, Taiwan, 11217
        • Research Site
  • United Kingdom
      • Bristol, United Kingdom, BS10 5NB
        • Research Site
      • Carshalton, United Kingdom, SM5 1AA
        • Research Site
      • Exeter, United Kingdom, EX2 5DW
        • Research Site
      • Leicester, United Kingdom, LE3 9QP
        • Research Site
      • Liverpool, United Kingdom, L7 8XP
        • Research Site
      • London, United Kingdom, SE5 9RS
        • Research Site
      • London, United Kingdom, SE1 9RT
        • Research Site
      • London, United Kingdom, NW3 2QG
        • Research Site
      • London, United Kingdom, SW17 0QT
        • Research Site
      • London, United Kingdom, NW1 2BH
        • Research Site
      • Manchester, United Kingdom, M13 9WL
        • Research Site
      • Newcastle-upon-Tyne, United Kingdom, NE1 4LP
        • Research Site
      • Nottingham, United Kingdom, NG5 1PB
        • Research Site
      • Oxford, United Kingdom, OX3 9DU
        • Research Site
      • Salford, United Kingdom, M6 8HD
        • Research Site
      • Stevenage, United Kingdom, SG1 4AB
        • Research Site
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Research Site
    • California
      • Orange, California, United States, 92868
        • Research Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Research Site
    • Florida
      • Gainesville, Florida, United States, 32610
        • Research Site
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Research Site
      • Louisville, Kentucky, United States, 40202
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Research Site
      • Boston, Massachusetts, United States, 02115
        • Research Site
      • Boston, Massachusetts, United States, 02118
        • Research Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Research Site
    • New York
      • New York, New York, United States, 10032
        • Research Site
      • Valhalla, New York, United States, 10595
        • Research Site
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • Research Site
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Research Site
      • Cleveland, Ohio, United States, 44106
        • Research Site
      • Columbus, Ohio, United States, 43203
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Research Site
      • Pittsburgh, Pennsylvania, United States, 15212
        • Research Site
    • Utah
      • Salt Lake City, Utah, United States, 84115
        • Research Site
    • West Virginia
      • Morgantown, West Virginia, United States, 26505
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 18 years of age or older
  2. Body weight ≥ 30 kilograms
  3. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab
  4. TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)
  5. Vaccinated against meningococcal infection (Neisseria meningitidis), within 3 years prior to, or at the time of, randomization. Participants who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive appropriate prophylactic antibiotics for at least 2 weeks after the vaccination. If participant cannot receive the meningococcal vaccine, then participant must be willing to receive antibiotic prophylaxis coverage against N. meningitidis during the entire Treatment Period and for 8 months following the final dose of study drug. Additional vaccination (Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae) may be considered based on individual patient condition.

Exclusion Criteria:

  1. Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)
  2. Postpartum aHUS
  3. Known chronic kidney disease
  4. TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening
  5. Primary and secondary glomerular diseases other than lupus
  6. Diagnosis of primary antiphospholipid antibody syndrome
  7. Shiga toxin-producing Escherichia coli infections including but not limited to Shiga toxin-related hemolytic uremic syndrome
  8. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity < 5%)
  9. Positive direct Coombs test which in the judgement of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA
  10. Clinical diagnosis of disseminated intravascular coagulation (DIC) in the judgement of the Investigator
  11. Presence of sepsis requiring vasopressors within 7 days prior to or during Screening
  12. Presence of monoclonal gammopathy including but not limited to multiple myeloma
  13. Known bone marrow insufficiency or failure evidenced by cytopenias
  14. Unresolved N. meningitidis infection
  15. History of malignancy within 5 years of Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence
  16. Use of any complement inhibitors within the past 3 years
  17. Respiratory failure requiring mechanical ventilation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Other: Placebo
Matching placebo
Other: Best Supportive Care
Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).
Experimental: Ravulizumab
Biological: Ravulizumab
Body weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.
Other Names:
  • Ultomiris
  • ALXN1210
Other: Best Supportive Care
Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
Time Frame: Week 26
TMA response required the following: 1) Normalization of platelet count without transfusion support during the prior 7 days. 2) Normalization of LDH. 3) Improvement in glomerular filtration rate (eGFR) of >= 30% compared to baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, and any measurement in between.
Week 26

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Complete TMA Response
Time Frame: Baseline through Week 26
The Kaplan-Meier estimate of time to event of complete TMA response is reported. TMA response required the following: 1) Normalization of platelet count without transfusion support during the prior 7 days. 2) Normalization of LDH. 3) Improvement in eGFR of >= 30% compared to baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, and any measurement in between. Participants who did not have a response were censored at the date of last visit or study discontinuation at the time when the analysis was performed.
Baseline through Week 26
Number of Participants With Hematologic Response at Week 26
Time Frame: Week 26
Hematologic response required the following: (1) Normalization of platelet count without transfusion support during the prior 7 days, and (2) normalization of LDH.
Week 26
Number of Participants With Renal Response at Week 26
Time Frame: Week 26
Renal response is improvement in eGFR of >= 30% compared to baseline. If a participant is on dialysis ≤5 days prior to the date of eGFR assessment, the eGFR will be set to 10 milliliter/minute/1.73 meter square (mL/min/1.73 m^2) for that assessment. If a participant is on dialysis during the entire 26 week randomized Treatment Period, or through early discontinuation of study drug, then the change in eGFR was not calculated.
Week 26
Number of Participants On Dialysis at Week 26
Time Frame: Week 26
Week 26
Change From Baseline in eGFR at Week 26
Time Frame: Baseline, Week 26
If a participant is on dialysis during the entire 26 week randomized Treatment Period, or through early discontinuation of study drug, then the change in eGFR was not calculated.
Baseline, Week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alexion Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 29, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 22, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 22, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 28, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 8, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 1, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ALXN1210-TMA-315
  • 2020-005328-13 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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