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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prospective, Single-Arm, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Complement Inhibitor Treatment-Naïve Pediatric and Adult Participants With Atypical Hemolytic Uremic Syndrome (aHUS) in China

Conditions
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Atypical Hemolytic Uremic

Intervention / Treatment
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* Drug: Eculizumab


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

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eculizumab<br>Participants will receive Eculizumab in a single dose vial. | Drug: Eculizumab<br>* Weight-based doses of Eculizumab will be administered intravenously as an induction dose followed by maintenance dose at Day 8, 15, or 29 depending on weight; then every 2 or 3 weeks, depending upon weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Considered as Complete Thrombotic Microangiopathy (TMA) Responders | To assess the efficacy of eculizumab in the treatment of participants with aHUS | Baseline through Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | To characterize the safety and tolerability of eculizumab in participants with aHUS | Baseline through Week 26 | 
| Pharmacokinetics (PK): Serum Eculizumab Concentration | To characterize the pharmacokinetics of eculizumab in participants with aHUS | Baseline through Week 26 (predose and postdose) | 
| Change From Baseline in Serum Free and Total Complement 5 (C5) Concentration at Week 26 | To characterize the pharmacodynamics of eculizumab in participants with aHUS | Baseline through Week 26 (predose and postdose) | 
| Number of Participants With Positive Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) to Eculizumab | To characterize the immunogenicity of eculizumab in participants with aHUS | Baseline through Week 26 | 
| Time to Complete TMA Response | To characterize the immunogenicity of eculizumab in participants with aHUS | Baseline through Week 26 | 
| Number of Participants Requiring Dialysis | To evaluate the efficacy of eculizumab | Baseline through Week 26 | 
| Number of Participants Classified as Improved, Stable (No Change), or Worsened Per Chronic Kidney Disease (CKD) Stage Classification | To evaluate the efficacy of eculizumab | Baseline through Week 26 | 
| Number of participants observed value and change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at visits | To evaluate the efficacy of eculizumab | Baseline through Week 26 | 
| Number of participants Increase in hemoglobin of ≥ 20 g/L | To evaluate the efficacy of eculizumab | baseline through Week 26 | 
| Number of participants Changes from baseline in vital signs and laboratory parameters at scheduled visits | To characterize the safety profile of eculizumab by additional safety measures | baseline through week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atypical hemolytic uremic, aHUS