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Eculizumab in Pediatric and Adult Participants With Atypical Hemolytic Uremic Syndrome (aHUS) in China

Phase 3
Active, not recruiting
Conditions
Atypical Hemolytic Uremic
Interventions
Registration Number
NCT05876351
Lead Sponsor
Alexion Pharmaceuticals, Inc.
Brief Summary

This is a Phase 3b, open-label, single-arm, multicenter study to evaluate the efficacy and safety of eculizumab in participants with atypical hemolytic uremic syndrome (aHUS) in China

Detailed Description

This is a Phase 3b, open-label, single-arm, multicenter study to evaluate the efficacy and safety of eculizumab in participants with aHUS in China. The study will be conducted in participants of any age who weigh ≥ 5 kg and who previously have not been treated with complement inhibitors. The study consists of an up to 7-day Screening Period and a 26-week Treatment Period. An 8-week Safety Follow-up Phone Call will be required only for participants who discontinue eculizumab treatment during the study or for participants who will not receive continued access to eculizumab after completing study treatment. Approximately 25 eligible participants in China will be enrolled.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
25
Inclusion Criteria
  1. Any age weighing ≥ 5 kg
  2. Complement treatment naïve with evidence of TMA.
  3. History of aHUS prior to kidney transplant,or persistent evidence of TMA at least 4 days after modifying the immunosuppressive regimen.
  4. Among participants with onset of TMA postpartum, persistent evidence of TMA for > 3 days after the day of childbirth
  5. All participants must be vaccinated against N meningitidis if not already vaccinated within the time period of active coverage specified by the vaccine manufacturer.
  6. Participants < 18 years of age must have been vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae according to local vaccination schedule guidelines.
  7. In participants receiving treatment with medications known to cause TMA, persistent evidence of TMA at least 4 days after modifying the excluded medication
Exclusion Criteria
  1. Known familial or acquired ADAMTS13deficiency (activity < 5%).
  2. ST-HUS as demonstrated by local guidelines.
  3. Positive direct Coombs test which is indicative of a clinically significant immune-mediated hemolysis not due to aHUS.
  4. HIV infection, and /or unresolved meningococcal disease
  5. Ongoing sepsis, and / or presence or suspicion of active and untreated systemic infection
  6. Organ transplantation history, and/or Bone marrow transplant/hematopoietic stem cell transplant within 6 months prior to the start of Screening.
  7. Among participants with a kidney transplant, acute kidney dysfunction within 4 weeks of transplant consistent with the diagnosis of acute antibody-mediated rejection.
  8. Among participants without a kidney transplant, history of kidney disease other than aHUS
  9. Identified drug exposure-related HUS, and / or HUS related to vitamin B12 deficiency and / or known genetic defects of cobalamin C metabolism.
  10. History of malignancy within 5 years of Screening.
  11. Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome.
  12. Chronic dialysis.
  13. Prior use of complement inhibitors.
  14. Use of tranexamic acid within 7 days prior to the start of Screening.
  15. Other immunosuppressive therapies.
  16. Receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks prior to the start of Screening.
  17. Received vasopressors or inotropes within 7 days prior to Screening.
  18. Previously or currently treated with a complement inhibitor.
  19. Has participated in another interventional treatment study or used any experimental therapy.
  20. Hypersensitivity to any excipient in eculizumab.
  21. Pregnant or breastfeeding.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
EculizumabEculizumabParticipants will receive Eculizumab in a single dose vial.
Primary Outcome Measures
NameTimeMethod
Number of Participants Considered as Complete Thrombotic Microangiopathy (TMA) RespondersBaseline through Week 26

To assess the efficacy of eculizumab in the treatment of participants with aHUS

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)Baseline through Week 26

To characterize the safety and tolerability of eculizumab in participants with aHUS

Change From Baseline in Serum Free and Total Complement 5 (C5) Concentration at Week 26Baseline through Week 26 (predose and postdose)

To characterize the pharmacodynamics of eculizumab in participants with aHUS

Number of Participants With Positive Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) to EculizumabBaseline through Week 26

To characterize the immunogenicity of eculizumab in participants with aHUS

Time to Complete TMA ResponseBaseline through Week 26

To characterize the immunogenicity of eculizumab in participants with aHUS

Number of Participants Requiring DialysisBaseline through Week 26

To evaluate the efficacy of eculizumab

Number of participants observed value and change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at visitsBaseline through Week 26

To evaluate the efficacy of eculizumab

Number of participants Increase in hemoglobin of ≥ 20 g/Lbaseline through Week 26

To evaluate the efficacy of eculizumab

Pharmacokinetics (PK): Serum Eculizumab ConcentrationBaseline through Week 26 (predose and postdose)

To characterize the pharmacokinetics of eculizumab in participants with aHUS

Number of Participants Classified as Improved, Stable (No Change), or Worsened Per Chronic Kidney Disease (CKD) Stage ClassificationBaseline through Week 26

To evaluate the efficacy of eculizumab

Number of participants Changes from baseline in vital signs and laboratory parameters at scheduled visitsbaseline through week 26

To characterize the safety profile of eculizumab by additional safety measures

Trial Locations

Locations (1)

Research Site

🇨🇳

Wuhan, China

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