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

Sponsor

Alexion (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05876351

Collaborator

AstraZeneca (Industry)

Enrollment

Locations

Arm

31.2

Anticipated Duration (Months)

1.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atypical Hemolytic Uremic	Drug: Eculizumab	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

open-label studyopen-label study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 24, 2023

Anticipated Primary Completion Date :

Mar 31, 2026

Anticipated Study Completion Date :

Mar 31, 2026

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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
Pharmacokinetics (PK): Serum Eculizumab Concentration [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 [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 [Baseline through Week 26]
To characterize the immunogenicity of eculizumab in participants with aHUS
Time to Complete TMA Response [Baseline through Week 26]
To characterize the immunogenicity of eculizumab in participants with aHUS
Number of Participants Requiring Dialysis [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 [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 [Baseline through Week 26]
To evaluate the efficacy of eculizumab
Number of participants Increase in hemoglobin of ≥ 20 g/L [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 [baseline through week 26]
To characterize the safety profile of eculizumab by additional safety measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Beijing	China	100034
2	Research Site	Beijing	China	100045
3	Research Site	Changsha	China	410007
4	Research Site	Chengdu	China	610041
5	Research Site	Guangzhou	China	510062
6	Research Site	Nanchang	China	330006
7	Research Site	Nanjing	China	210002
8	Research Site	Qingdao	China	110016
9	Research Site	Shenzhen	China	518036
10	Research Site	Suzhou	China	215002
11	Research Site	Taiyuan	China	030012
12	Research Site	Wuhan	China	430030
13	Research Site	Yantai	China	264000
14	Research Site	Zhengzhou	China	450018
15	Research Site	Zhengzhou	China	450052