E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atypical Hemolytic Uremic Syndrome (aHUS) |
|
E.1.1.1 | Medical condition in easily understood language |
Atypical Hemolytic Uremic Syndrome (aHUS) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019515 |
E.1.2 | Term | Hemolytic uremic syndrome |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy of ALXN1210 in complement inhibitor treatment naïve pediatric patients (ie, Cohort 1). |
|
E.2.2 | Secondary objectives of the trial |
To assess in both complement inhibitor naïve pediatric patients (ie, Cohort 1) and complement inhibitor experienced adolescent (i.e. Cohort 2):
- The safety and tolerability of ALXN1210
- Additional efficacy measures |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Complete TMA Response (only for Cohort 1) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Dialysis requirement status
- Time to Complete TMA Response (only for Cohort 1)
- Complete TMA Response status over time (only for Cohort 1)
- Observed value and change from baseline in estimated glomerular filtration rate (eGFR)
- Change from baseline in chronic kidney disease (CKD) stage
- Change from baseline in hematologic parameters (platelets, LDH, hemoglobin)
- Increase in hemoglobin of ≥ 20 g/L from baseline
- Change from baseline in quality of life as measured by Pediatric FACIT Fatigue questionnaire (patients ≥ 5 years of age)
-TMA parameters in patients who discontinue treatment in the Extension Period, but remain in the study |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Canada |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Russian Federation |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LVLS or follow-up (whether on site or via phone call) in the extension period, whichever is later. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |