Thrombotic MicroangiopathiesPhase 2NCT03518203
Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
A Phase 2 study testing Eculizumab in people with Thrombotic Microangiopathies and Atypical Hemolytic Uremic Syndrome, run by Children's Hospital Medical Center, Cincinnati at 3 sites in United States.
Trial summary
Hematopoietic stem cell transplantation (HCT)-associated thrombotic microangiopathy (TMA) is an understudied complication of HCT that significantly affects transplant related morbidity and mortality. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome, Multiple Organ Dysfunction Syndrome
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 3 sitesUnited States
- Study dates
- 3 Aug 2018to 1 Jun 2022
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients of any age undergoing allogeneic or autologous HCT
- Histologic TMA diagnosis OR clinical TMA diagnosis and presenting with high risk disease features including elevated plasma sC5b-9 above laboratory normal value (≥244ng/ml) and proteinuria measured as ≥30mg/dL of protein on random urinalysis x2 or protein/creatinine ratio ≥1mg/mg or patient receiving renal replacement therapy.
- Minimum weight of ≥ 5kg.
Who cannot join
- Known hypersensitivity to any constituent of the study medication.
- Subjects with unresolved serious Neisseria meningitides infection or progressive severe infection.
- Patients with diagnosis of TTP as defined by ADAMST13 activity test <10%.
- Patients previously treated with eculizumab or other complement blocker for TMA within the 60 days prior to first dose of study treatment.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Hospital Los Angeles (CHLA)
Los Angeles, California, 90027
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
About this study
Official title: Early Intervention With Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome (TMA/aHUS)-Associated Multiple Organ Dysfunction Syndrome (MODS) in Hematopoietic Stem Cell Transplant (HCT) Recipients
Hematopoietic stem cell transplantation (HCT)-associated thrombotic microangiopathy (TMA) is an understudied complication of HCT that significantly affects transplant related morbidity and mortality. The investigators hypothesize that early intervention with complement blocker eculizumab will double survival in HCT recipients with high risk TMA, as compared to historical untreated controls. An optimal eculizumab dosing schedule can be determined for this population through eculizumab pharmacokinetic/pharmacodynamic (PK/PD) testing.
Read the detailed description
This clinical trial is a prospective single arm multi-institution study in children and young adults undergoing allogeneic or autologous hematopoietic stem cell transplantation who will receive early therapy with eculizumab to prevent TMA-associated MODS after transplantation. The purpose of this research study is to examine efficacy of complement blocker eculizumab in HCT recipients with high risk TMA and to determine optimal eculizumab dosing regimen for HCT recipients with TMA using PK/PD studies. All patients will receive therapy based on their weight for 24 weeks. Survival will be assessed at 6 months from TMA diagnosis.
- Conditions
- Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome, Multiple Organ Dysfunction Syndrome
- Being tested
- Eculizumab
- Keywords
- Hematopoietic Stem Cell Transplant
- Medical subject headings
- Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome, Multiple Organ Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Also called Soliris
Eculizumab will be administered as intravenous infusion (IV) over 60 minutes. The dosage form will be 300 mg single-use vials each containing 30 mL of 10 mg/mL sterile, preservative-free solution.
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | All patients will receive eculizumab based on their weight for 24 weeks. Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Survival at 6 months after the date of TMA diagnosis
Measured: 6 months
Secondary outcomes (3)
Number of Participants With Organ Dysfunction
Number of participants with organ dysfunction at 6 months after TMA diagnosis. Organ dysfunction definitions are listed in the protocol Appendix II that is uploaded to ClinicalTrials.gov site.
Measured: 6 months
Number of Participants With Organ Dysfunction
Number of participants with organ dysfunction at 1 year after TMA diagnosis. Organ dysfunction definitions are listed in the protocol Appendix II that is uploaded to ClinicalTrials.gov site.
Measured: 1 year
Non-relapse Mortality
Non-relapse mortality descriptively compared with historical controls at 1 year
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2018
- Study start3 Aug 2018
- Primary completion4 Apr 2022
- Study completion1 Jun 2022
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 MicroangiopathiesStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sonata Jodele, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03518203
- Sponsor's protocol ID
- 2018-7119C
- Status last verified
- Aug 2023
- First submitted
- 5 Mar 2018
- Last updated
- 21 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Jodele S, Dandoy CE, Aguayo-Hiraldo P, Lane A, Teusink-Cross A, Sabulski A, Mizuno K, Laskin BL, Freedman J, Davies SM. A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation-associated TMA. Blood. 2024 Mar 21;143(12):1112-1123. doi: 10.1182/blood.2023022526.
PubMed 37946262
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Intervention With Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome (TMA/aHUS)-Associated Multiple Organ Dysfunction Syndrome (MODS) in Hematopoietic Stem Cell Transplant (HCT) Recipients
- ClinicalTrials.gov ID
- NCT03518203
- Acronym / sponsor ID
- 2018-7119C
- Conditions
- Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome, Multiple Organ Dysfunction Syndrome
- Keywords
- Hematopoietic Stem Cell Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 3 Aug 2018 (actual)
- Primary completion
- 4 Apr 2022 (actual)
- Study completion
- 1 Jun 2022 (actual)
- First posted
- 8 May 2018 (actual)
- Results
- Posted 21 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hematopoietic stem cell transplantation (HCT)-associated thrombotic microangiopathy (TMA) is an understudied complication of HCT that significantly affects transplant related morbidity and mortality. The investigators hypothesize that early intervention with complement blocker eculizumab will double survival in HCT recipients with high risk TMA, as compared to historical untreated controls. An optimal eculizumab dosing schedule can be determined for this population through eculizumab pharmacokinetic/pharmacodynamic (PK/PD) testing.
Detailed description
This clinical trial is a prospective single arm multi-institution study in children and young adults undergoing allogeneic or autologous hematopoietic stem cell transplantation who will receive early therapy with eculizumab to prevent TMA-associated MODS after transplantation. The purpose of this research study is to examine efficacy of complement blocker eculizumab in HCT recipients with high risk TMA and to determine optimal eculizumab dosing regimen for HCT recipients with TMA using PK/PD studies. All patients will receive therapy based on their weight for 24 weeks. Survival will be assessed at 6 months from TMA diagnosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: EculizumabAll patients will receive eculizumab based on their weight for 24 weeks. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients of any age undergoing allogeneic or autologous HCT
- Histologic TMA diagnosis OR clinical TMA diagnosis and presenting with high risk disease features including elevated plasma sC5b-9 above laboratory normal value (≥244ng/ml) and proteinuria measured as ≥30mg/dL of protein on random urinalysis x2 or protein/creatinine ratio ≥1mg/mg or patient receiving renal replacement therapy.
- Minimum weight of ≥ 5kg.
Key exclusion criteria (4 listed)
- Known hypersensitivity to any constituent of the study medication.
- Subjects with unresolved serious Neisseria meningitides infection or progressive severe infection.
- Patients with diagnosis of TTP as defined by ADAMST13 activity test <10%.
- Patients previously treated with eculizumab or other complement blocker for TMA within the 60 days prior to first dose of study treatment.
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 |
|---|---|---|
| EculizumabAlso: SolirisEculizumab will be administered as intravenous infusion (IV) over 60 minutes. The dosage form will be 300 mg single-use vials each containing 30 mL of 10 mg/mL sterile, preservative-free solution. | Drug | Eculizumab |
Primary outcome
Survival
Time frame: 6 months
Survival at 6 months after the date of TMA diagnosis
3 secondary outcomes
Number of Participants With Organ Dysfunction
Time frame: 6 months
Number of Participants With Organ Dysfunction
Time frame: 1 year
Non-relapse Mortality
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37946262Jodele S, Dandoy CE, Aguayo-Hiraldo P, Lane A, Teusink-Cross A, Sabulski A, Mizuno K, Laskin BL, Freedman J, Davies SM. A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation-associated TMA. Blood. 2024 Mar 21;143(12):1112-1123. doi: 10.1182/blood.2023022526.
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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.
Sonata Jodele, MD principal investigator
Children's Hospital Medical Center, Cincinnati
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eculizumab in people with Thrombotic Microangiopathies and Atypical Hemolytic Uremic Syndrome, run by Children's Hospital Medical Center, Cincinnati at 3 sites in United States.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 21 Sep 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?
Survival (time frame: 6 months). 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 NCT03518203, 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 21 Sep 2023; AzTrials last refreshed its copy on 8 Nov 2026.