Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients

Atypical Hemolytic Uremic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03518203
• Other study ID #: 2018-7119C
• Status: Completed
• Phase: Phase 2
• Start date: August 3, 2018
• Est. completion date: June 1, 2022

Study information

• Verified date: August 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 1, 2022
• Est. primary completion date: April 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Atypical Hemolytic Uremic Syndrome
• Azotemia
• Hemolysis
• Hemolytic-Uremic Syndrome
• Multiple Organ Dysfunction Syndrome
• Multiple Organ Failure
• Syndrome
• Thrombotic Microangiopathies
• Vascular Diseases

Intervention

Drug:
• Eculizumab
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.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital Los Angeles (CHLA)	Los Angeles	California
United States	Children's Hospital of Philadelphia (CHOP)	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	Survival at 6 months after the date of TMA diagnosis	6 months
Secondary	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.	6 months
Secondary	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.	1 year
Secondary	Non-relapse Mortality	Non-relapse mortality descriptively compared with historical controls at 1 year	1 year