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

• Register: ClinicalTrials.gov
• Last refreshed on: 25 March 2024
• Main ID: NCT03131219
• Date of registration: 24/04/2017
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, Inc.
• Public title: Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
• Scientific title: A Phase 3, Open-Label, Multicenter Study of ALXN1210 in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
• Date of first enrolment: August 31, 2017
• Target sample size: 34
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03131219
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Belgium, Germany, Italy, Japan, Korea, Republic of, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

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.



Age minimum: N/A
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Atypical Hemolytic Uremic Syndrome (aHUS)

Intervention(s)

Biological: Ravulizumab

Primary Outcome(s)

Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 [Time Frame: Week 26]

Secondary Outcome(s)

Time To Complete TMA Response In Complement Inhibitor Treatment-naïve Participants [Time Frame: Baseline through at least Week 52 and up to Week 111]

Participants With Change From Baseline In CKD Stage At Weeks 26 and 52 [Time Frame: Baseline, Week 26, and Week 52]

Change From Baseline In Platelet Count At Weeks 26 and 52 [Time Frame: Baseline, Week 26 and Week 52]

Change From Baseline In eGFR At Weeks 26 and 52 [Time Frame: Baseline, Week 26 and Week 52]

Change From Baseline In LDH At Weeks 26 and 52 [Time Frame: Baseline, Week 26 and Week 52]

Participants Who Do Not Require Dialysis at Weeks 26 and 52 [Time Frame: Week 26 and Week 52]

Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52 [Time Frame: Week 52]

Change From Baseline In Hemoglobin At Weeks 26 and 52 [Time Frame: Baseline, Week 26 and Week 52]

Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire (Participants =5 Years Of Age) At Weeks 26 and 52 [Time Frame: Baseline, Week 26 and Week 52]

Percentage Of Complement Inhibitor Treatment-naïve Participants With An Increase From Baseline In Hemoglobin =20 g/L Through Week 26 and Week 52 [Time Frame: Baseline through Week 26 and through Week 52]

Secondary ID(s)

ALXN1210-aHUS-312

2016-002499-29

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/09/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03131219