Study of ALXN1210 in Children and Adolescents with Atypical Hemolytic Uremic Syndrome (aHUS)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 31

Inclusion Criteria

Cohort 1 inclusion criteria:
1. Patients from birth up to < 18 years of age and weighing = 5 kg at the time of consent.
2. Evidence of thrombotic microangiopathy (TMA), including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
3. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae
4. Female patients of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ALXN1210

Cohort 2 inclusion criteria:
1. Patients between 12 and <18 years of age who have been treated with eculizumab for aHUS for at least 90 days prior to Screening
2. Patients with a documented diagnosis of aHUS
3. Patients with clinical evidence of response to eculizumab indicated by stable TMA parameters at Screening
4. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and
Haemophilus influenzae
5. Female patients of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ALXN1210
Are the trial subjects under 18? yes
Number of subjects for this age range: 23
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. ADAMTS13 deficiency (Activity < 5%)
2. Shiga toxin-related hemolytic uremic syndrome (STEC-HUS)
3. Positive direct Coombs test
4. Females who plan to become pregnant during the study or are currently pregnant or breastfeeding
5. Identified drug exposure-related hemolytic uremic syndrome (HUS)
6. Bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT) within last 6 months prior to start of Screening
7. HUS related known genetic defects of cobalamin C metabolism
8. Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome
9. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for ESKD)
10. For Cohort 2 patients, prior use of complement inhibitors other than eculizumab.
11. For Cohort 2 patients, any known abnormal TMA parameters within 90 days prior to Screening

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy of ALXN1210 in complement inhibitor treatment naïve pediatric patients (ie, Cohort 1).;Secondary Objective: To assess in both complement inhibitor naïve pediatric patients (ie, Cohort 1) and complement inhibitor experienced adolescent (i.e. Cohort 2):<br>- Safety and tolerability of ALXN1210<br>- Additional efficacy measures;Primary end point(s): Complete TMA Response (only for Cohort 1);Timepoint(s) of evaluation of this end point: Week 26

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Dialysis requirement status<br>- Time to Complete TMA Response (only for Cohort 1)<br>- Complete TMA Response status over time (only for Cohort 1)<br>- Observed value and change from baseline in estimated glomerular filtration rate (eGFR) <br>- Change from baseline in chronic kidney disease (CKD) stage<br>- Change from baseline in hematologic parameters (platelets, LDH, hemoglobin)<br>- Increase in hemoglobin of = 20 g/L from baseline<br>- Change from baseline in quality of life as measured by Pediatric FACIT Fatigue questionnaire (patients = 5 years of age) <br>-TMA parameters in patients who discontinue treatment in the Extension Period, but remain in the study;Timepoint(s) of evaluation of this end point: Week 26