Clinical trial NCT05876351: Eculizumab in Pediatric and Adult Participants With Atypical Hemolytic Uremic Syndrome (aHUS) in China
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atypical Hemolytic Uremic
Keywords: atypical hemolytic uremic
aHUS
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2023-05-25
Enrollment: 25
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open-label study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Considered as Complete Thrombotic Microangiopathy (TMA) Responders
timeFrame: Baseline through Week 26
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline through Week 26
measure: Pharmacokinetics (PK): Serum Eculizumab Concentration
timeFrame: Baseline through Week 26 (predose and postdose)
measure: Change From Baseline in Serum Free and Total Complement 5 (C5) Concentration at Week 26
timeFrame: Baseline through Week 26 (predose and postdose)
measure: Number of Participants With Positive Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) to Eculizumab
timeFrame: Baseline through Week 26
measure: Time to Complete TMA Response
timeFrame: Baseline through Week 26
measure: Number of Participants Requiring Dialysis
timeFrame: Baseline through Week 26
measure: Number of Participants Classified as Improved, Stable (No Change), or Worsened Per Chronic Kidney Disease (CKD) Stage Classification
timeFrame: Baseline through Week 26
measure: Number of participants observed value and change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at visits
timeFrame: Baseline through Week 26
measure: Number of participants Increase in hemoglobin of ≥ 20 g/L
timeFrame: baseline through Week 26
measure: Number of participants Changes from baseline in vital signs and laboratory parameters at scheduled visits
timeFrame: baseline through week 26
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
Study officials:
References: