Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)

Alexion Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Atypical Hemolytic Uremic Syndrome (aHUS)

Treatments: Biological: Ravulizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03131219

2016-002499-29 (EudraCT Number)

ALXN1210-aHUS-312

Details and patient eligibility

About

The purpose of the study is to assess the efficacy of ravulizumab to control disease activity in children and adolescents with aHUS who have not previously used a complement inhibitor (complement inhibitor treatment-naïve), as well as in complement inhibitor-experienced (eculizumab-experienced) adolescent participants.

Enrollment: 34 patients

Sex: All

Ages: Under 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Complement Inhibitor Treatment Naïve:

1. Participants from birth up to <18 years of age and weighing ≥5 kilograms (kg) at the time of consent.
2. Participants had not been previously treated with complement inhibitors.
3. Evidence of thrombotic microangiopathy (TMA), including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
4. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
5. Female participants of childbearing potential and male participants with female partners of childbearing potential must have used highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

Eculizumab Experienced:

1. Participants between 12 and <18 years of age (non-Japanese sites) or <18 years of age (Japanese sites) who had been treated with eculizumab according to the labelled dosing recommendation for aHUS for at least 90 days prior to screening.
2. Participants with documented diagnosis of aHUS.
3. Participants 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 type b.
5. Females of childbearing potential and male participants with female partners of childbearing potential must have used highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

Exclusion criteria

1. Known familial or acquired ADAMTS13 ("a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13") deficiency (activity <5%).
2. Known Shiga toxin-related hemolytic uremic syndrome.
3. Positive direct Coombs test.
4. Females who planned to become pregnant during the study or were currently pregnancy or breastfeeding.
5. Identified drug exposure-related hemolytic uremic syndrome.
6. Bone marrow transplant/hematopoietic stem cell transplant within the last 6 months prior to the start of screening.
7. Hemolytic uremic syndrome related to known genetic defects of cobalamin C metabolism.
8. Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome.
9. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease.
10. For eculizumab-experienced participants, prior use of complement inhibitors other than eculizumab.
11. For eculizumab-experienced participants, any known abnormal TMA parameters within 90 days prior to screening.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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34 participants in 1 patient group

Ravulizumab

Experimental group

Description:

Participants were administered weight-based doses of ravulizumab every 8 weeks thereafter for participants weighing ≥ 20 kg, or once every 4 weeks for participant weighing \< 20 kg, for a total of 26 weeks of study treatment in the initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participant continued their weight-based maintenance dose until the product was registered or approved (in accordance with country specific regulation) or for up to 4.5 years, whichever occurred first.

Treatment:

Biological: Ravulizumab