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

Overview

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.

Full Title of Study: “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”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: March 31, 2026

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.

Interventions

• Drug: Eculizumab
  • 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.

Arms, Groups and Cohorts

• Experimental: Eculizumab
  • Participants will receive Eculizumab in a single dose vial.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Alexion
• Collaborator
  • AstraZeneca
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Contact(s)
  • AstraZeneca Clinical Study Information Center, 1-877-240-9479, information.center@astrazeneca.com