Clinical trial NCT03131219: Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
Official title: A Phase 3, Open-Label, Multicenter Study of ALXN1210 in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atypical Hemolytic Uremic Syndrome (aHUS)
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-04-27
Enrollment: 34
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Time To Complete TMA Response In Complement Inhibitor Treatment-naïve Participants
timeFrame: Baseline through at least Week 52 and up to Week 111
measure: Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52
timeFrame: Week 52
measure: Participants Who Do Not Require Dialysis at Weeks 26 and 52
timeFrame: Week 26 and Week 52
measure: Change From Baseline In eGFR At Weeks 26 and 52
timeFrame: Baseline, Week 26 and Week 52
measure: Participants With Change From Baseline In CKD Stage At Weeks 26 and 52
timeFrame: Baseline, Week 26, and Week 52
measure: Change From Baseline In Platelet Count At Weeks 26 and 52
timeFrame: Baseline, Week 26 and Week 52
measure: Change From Baseline In LDH At Weeks 26 and 52
timeFrame: Baseline, Week 26 and Week 52
measure: Change From Baseline In Hemoglobin At Weeks 26 and 52
timeFrame: Baseline, Week 26 and Week 52
measure: Percentage Of Complement Inhibitor Treatment-naïve Participants With An Increase From Baseline In Hemoglobin ≥20 g/L Through Week 26 and Week 52
timeFrame: Baseline through Week 26 and through Week 52
measure: 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
timeFrame: Baseline, Week 26 and Week 52
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Brussels
country: Belgium
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Jeju-do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Yangsan-si
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Esplugues de Llobregat
country: Spain
facility: Research Site
city: La Coruna
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: Rondeau E, Scully M, Ariceta G, Barbour T, Cataland S, Heyne N, Miyakawa Y, Ortiz S, Swenson E, Vallee M, Yoon SS, Kavanagh D, Haller H; 311 Study Group. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naive to complement inhibitor treatment. Kidney Int. 2020 Jun;97(6):1287-1296. doi: 10.1016/j.kint.2020.01.035. Epub 2020 Mar 6.
citation: Pugh D, O'Sullivan ED, Duthie FA, Masson P, Kavanagh D. Interventions for atypical haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Mar 23;3(3):CD012862. doi: 10.1002/14651858.CD012862.pub2.
citation: Tanaka K, Adams B, Aris AM, Fujita N, Ogawa M, Ortiz S, Vallee M, Greenbaum LA. The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. Pediatr Nephrol. 2021 Apr;36(4):889-898. doi: 10.1007/s00467-020-04774-2. Epub 2020 Oct 13.