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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Atypical Hemolytic Uremic
• Intervention / Treatment: Drug: Eculizumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• China
  • Beijing, China, 100034
    • Recruiting
    • Research Site
  • Beijing, China, 100045
    • Recruiting
    • Research Site
  • Changsha, China, 410007
    • Recruiting
    • Research Site
  • Chengdu, China, 610041
    • Recruiting
    • Research Site
  • Guangzhou, China, 510062
    • Not yet recruiting
    • Research Site
  • Nanchang, China, 330006
    • Recruiting
    • Research Site
  • Nanjing, China, 210002
    • Recruiting
    • Research Site
  • Qingdao, China, 110016
    • Recruiting
    • Research Site
  • Shenzhen, China, 518036
    • Not yet recruiting
    • Research Site
  • Suzhou, China, 215002
    • Recruiting
    • Research Site
  • Taiyuan, China, 030012
    • Recruiting
    • Research Site
  • Wuhan, China, 430030
    • Recruiting
    • Research Site
  • Yantai, China, 264000
    • Not yet recruiting
    • Research Site
  • Zhengzhou, China, 450052
    • Recruiting
    • Research Site
  • Zhengzhou, China, 450018
    • Recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eculizumab; Participants will receive Eculizumab in a single dose vial.	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2023
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: aHUS; atypical hemolytic uremic
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Hematologic Diseases; Anemia; Thrombocytopenia; Blood Platelet Disorders; Anemia, Hemolytic; Thrombotic Microangiopathies; Uremia; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemolysis; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: D7413C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No