E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atypical Hemolytic Uremic Syndrome (aHUS) |
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E.1.1.1 | Medical condition in easily understood language |
Atypical Hemolytic Uremic Syndrome (aHUS) |
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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 |
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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 |
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E.2.2 | Secondary objectives of the trial |
Safety and tolerability of ALXN1210
Additional efficacy measures |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female ≥ 12 years of age and weighing ≥ 40 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 kidney injury.
3. Documented meningococcal vaccination not more than 3 years prior to dosing, under 18 also requiring 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 |
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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. Pregnancy 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 to vitamin B12 deficiency
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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Dialysis requirement status
- Time to Complete TMA Response
- Complete TMA Response status over time
- 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 ≥ 20g/L from baseline
- Change from baseline in quality of life, as measured by the EQ-5D-3L (all patients)
- Change from baseline in quality of life, as measured by the FACIT Fatigue Version 4 questionnaire (patients ≥ 18 years of age)
- Change from baseline in quality of life, as measured by the Pediatric FACIT Fatigue questionnaire (patients 12 to < 18 years of age)
-TMA parameters in patients who discontinue treatment but remain in the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
France |
Japan |
Korea, Republic of |
Spain |
United Kingdom |
United States |
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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
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |