Thrombotic MicroangiopathyPhase 3NCT04743804
Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger
A Phase 3 study testing Ravulizumab in people with Thrombotic Microangiopathy, run by Alexion Pharmaceuticals, Inc. at 97 sites in 13 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thrombotic Microangiopathy
- What is being tested?
- Ravulizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 97 sitesin 13 countries
- Study dates
- 29 Jun 2021to 22 Dec 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older
- Body weight ≥ 30 kilograms
- 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
- TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)
- 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.
Who cannot join
- Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)
- Postpartum aHUS
- Known chronic kidney disease
- TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening
- Primary and secondary glomerular diseases other than lupus
- Diagnosis of primary antiphospholipid antibody syndrome
Show all 17Show fewer
- Shiga toxin-producing Escherichia coli infections including but not limited to Shiga toxin-related hemolytic uremic syndrome
- Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity < 5%)
- Positive direct Coombs test which in the judgement of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA
- Clinical diagnosis of disseminated intravascular coagulation (DIC) in the judgement of the Investigator
- Presence of sepsis requiring vasopressors within 7 days prior to or during Screening
- Presence of monoclonal gammopathy including but not limited to multiple myeloma
- Known bone marrow insufficiency or failure evidenced by cytopenias
- Unresolved N. meningitidis infection
- 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
- Use of any complement inhibitors within the past 3 years
- Respiratory failure requiring mechanical ventilation
Trial locations and contacts
97 sites in 13 countries.
97 sites in 13 countries
United States20 sites
Research Site
Boston, Massachusetts, 02111
Research Site
Boston, Massachusetts, 02115
Research Site
Boston, Massachusetts, 02118
Research Site
Cleveland, Ohio, 44106
Research Site
Cleveland, Ohio, 44195
Research Site
Columbus, Ohio, 43203
Research Site
Gainesville, Florida, 32610
Research Site
Lexington, Kentucky, 40536
Research Site
Louisville, Kentucky, 40202
Research Site
Morgantown, West Virginia, 26505
Research Site
New York, New York, 10032
Research Site
Orange, California, 92868
Research Site
Philadelphia, Pennsylvania, 19107
Research Site
Pittsburgh, Pennsylvania, 15212
Research Site
Rochester, Minnesota, 55905
Research Site
Salt Lake City, Utah, 84115
Research Site
Tucson, Arizona, 85724
Research Site
Valhalla, New York, 10595
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Winston-Salem, North Carolina, 27103
United Kingdom16 sites
Research Site
Bristol, BS10 5NB
Research Site
Carshalton, SM5 1AA
Research Site
Exeter, EX2 5DW
Research Site
Leicester, LE3 9QP
Research Site
Liverpool, L7 8XP
Research Site
London, NW1 2BH
Research Site
London, NW3 2QG
Research Site
London, SE1 9RT
Research Site
London, SE5 9RS
Research Site
London, SW17 0QT
Research Site
Manchester, M13 9WL
Research Site
Newcastle upon Tyne, NE1 4LP
Research Site
Nottingham, NG5 1PB
Research Site
Oxford, OX3 9DU
Research Site
Salford, M6 8HD
Research Site
Stevenage, SG1 4AB
Japan10 sites
Research Site
Bunkyō City, 113-8431
Research Site
Iruma-Gun, 350-0495
Research Site
Mitaka-shi, 181-8611
Research Site
Miyazaki, 889-1692
Research Site
Nagoya, 466-8560
Research Site
Nagoya, 466-8650
Research Site
Osaka, 565-0871
Research Site
Sapporo, 060-8648
Research Site
Sendai, 980-8574
Research Site
Shinjuku-ku, 162-8666
Brazil9 sites
Research Site
Belo Horizonte, 30150-221
Research Site
Botucatu, 18618-687
Research Site
Campinas, 13083-894
Research Site
Fortaleza, 60430-375
Research Site
Porto Alegre, 90110-270
Research Site
Ribeirão Preto, 14051-040
Research Site
Salvador, 41253-190
Research Site
São Paulo, 04036-002
Research Site
São Paulo, 05403-000
South Korea8 sites
Research Site
Daegu, 42415
Research Site
Gwangju, 61469
Research Site
Seoul, 02841
Research Site
Seoul, 03080
Research Site
Seoul, 04401
Research Site
Seoul, 06973
Research Site
Seoul, 134-727
Research Site
Seoul, 6591
France7 sites
Research Site
Bordeaux, 33076
Research Site
Chambéry, 73011
Research Site
Lille, 59037
Research Site
Montpellier
Research Site
Paris, 75020
Research Site
Paris, 75571
Research Site
Tours, 37044
Taiwan6 sites
Research Site
Kaohsiung City, 81362
Research Site
Kaohsiung City, 833401
Research Site
New Taipei City, 23561
Research Site
Taichung, 40447
Research Site
Taichung, 40705
Research Site
Taipei, 11217
Belgium5 sites
Research Site
Belgium, 1200
Research Site
Brussels, 1070
Research Site
Edegem, 2650
Research Site
Leuven, 3000
Research Site
Liège, 4000
Canada4 sites
Research Site
Kingston, Ontario, K7L 3N6
Research Site
Montreal, Quebec, H2X 3E4
Research Site
Québec, Quebec, G1R 3S1
Research Site
Toronto, Ontario, M5B 1W8
Netherlands4 sites
Research Site
Amsterdam, 1100 DD
Research Site
Groningen, 9713 GZ
Research Site
Maastricht, 6229 HX
Research Site
Nijmegen, 6500 HB
Spain4 sites
Research Site
Barcelona, 08036
Research Site
Granada, 18014
Research Site
Las Palmas de Gran Canaria, 35016
Research Site
Madrid, 28040
About this study
Official title: 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.
- Conditions
- Thrombotic Microangiopathy
- Being tested
- Ravulizumab, Placebo, Best Supportive Care
- Keywords
- Complement, Trigger, Secondary thrombotic microangiopathy, Acute kidney injury
- Medical subject headings
- Thrombotic Microangiopathies, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RavulizumabBiological
Also called Ultomiris, ALXN1210
Body weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.
PlaceboOther
Matching placebo
Best Supportive CareOther
Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).
| Study group | Role | What they receive |
|---|---|---|
| Ravulizumab | Experimental | Not described Receives: Biological: Ravulizumab; Other: Best Supportive Care |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo; Other: Best Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at 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.
Measured: Week 26
Secondary outcomes (5)
Time to Complete TMA Response
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.
Measured: Baseline through Week 26
Number of Participants With Hematologic Response at 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.
Measured: Week 26
Number of Participants With Renal Response at 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.
Measured: Week 26
Number of Participants On Dialysis at Week 26
Measured: Week 26
Change From Baseline in eGFR at 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.
Measured: Baseline, Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2021
- Study start29 Jun 2021
- Primary completion22 Dec 2022
- Study completion22 Dec 2022
Why it stopped: Recruitment Challenges
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thrombotic MicroangiopathyStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04743804
- Sponsor's protocol ID
- ALXN1210-TMA-315
- Other IDs
- 2020-005328-13
- Status last verified
- Aug 2024
- First submitted
- 28 Jan 2021
- Last updated
- 1 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Werion A, Storms P, Zizi Y, Beguin C, Bernards J, Cambier JF, Dahan K, Dierickx D, Godefroid N, Hilbert P, Lambert C, Levtchenko E, Meyskens T, Poire X, van den Heuvel L, Claes KJ, Morelle J; UCLouvain TMA/HUS Network and KU Leuven TMA/HUS Network. Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies. Clin J Am Soc Nephrol. 2023 Jul 1;18(7):881-891. doi: 10.2215/CJN.0000000000000182. Epub 2023 Apr 21.
PubMed 37094330
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04743804
- Acronym / sponsor ID
- ALXN1210-TMA-315
- Conditions
- Thrombotic Microangiopathy
- Keywords
- Complement, Trigger, Secondary thrombotic microangiopathy, Acute kidney injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment Challenges
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Jun 2021 (actual)
- Primary completion
- 22 Dec 2022 (actual)
- Study completion
- 22 Dec 2022 (actual)
- First posted
- 8 Feb 2021 (actual)
- Results
- Posted 12 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ravulizumab | Experimental | Biological: Ravulizumab, Other: Best Supportive Care |
| Placebo | Placebo comparator | Other: Placebo, Other: Best Supportive Care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18 years of age or older
- Body weight ≥ 30 kilograms
- 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
- TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)
- 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.
Key exclusion criteria (17 listed)
- Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)
- Postpartum aHUS
- Known chronic kidney disease
- TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening
- Primary and secondary glomerular diseases other than lupus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RavulizumabAlso: Ultomiris, ALXN1210Body weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks. | Biological | Ravulizumab |
| PlaceboMatching placebo | Other | Placebo |
| Best Supportive CareParticipants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol). | Other | Placebo, Ravulizumab |
Primary outcome
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.
5 secondary outcomes
Time to Complete TMA Response
Time frame: Baseline through Week 26
Number of Participants With Hematologic Response at Week 26
Time frame: Week 26
Number of Participants With Renal Response at Week 26
Time frame: Week 26
Number of Participants On Dialysis at Week 26
Time frame: Week 26
Change From Baseline in eGFR at Week 26
Time frame: Baseline, Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37094330Werion A, Storms P, Zizi Y, Beguin C, Bernards J, Cambier JF, Dahan K, Dierickx D, Godefroid N, Hilbert P, Lambert C, Levtchenko E, Meyskens T, Poire X, van den Heuvel L, Claes KJ, Morelle J; UCLouvain TMA/HUS Network and KU Leuven TMA/HUS Network. Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies. Clin J Am Soc Nephrol. 2023 Jul 1;18(7):881-891. doi: 10.2215/CJN.0000000000000182. Epub 2023 Apr 21.
- Individual participant dataSharing planned: No
Related trials for Thrombotic Microangiopathy
Not yet recruitingPhase 1/2
TGD001 Treatment in Thrombotic Microangiopathies
Thrombotic Microangiopathies, ITP Immune-Mediated Thrombocytopenia
Recruiting
Safety and Efficacy of Iptacopan in Patients With High-Risk Transplantation-Associated Thrombotic Microangiopathy
Thrombotic Microangiopathy, Hematopoietic Stem Cell Transplantation (HSCT)
RecruitingPhase 2
Safety and Efficacy of Eculizumab in High-risk TA-TMA
Transplant-Associated Thrombotic Microangiopathy (TA-TMA)
Not yet recruiting
The Role of interferOn and Complement in SecondAry thRombotic micrioangiOpathy
Thrombotic Microangiopathies
RecruitingObservational study
TRANSPIRE: Lung Injury in a Longitudinal Cohort of Pediatric HSCT Patients
Hematopoietic Stem Cell Transplant (HSCT), Diffuse Alveolar Hemorrhage
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
97 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ravulizumab in people with Thrombotic Microangiopathy, run by Alexion Pharmaceuticals, Inc. at 97 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 97 sites in United States, United Kingdom, Japan, Brazil, South Korea and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 (time frame: Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04743804, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024; AzTrials last refreshed its copy on 26 Oct 2026.