Clinical trial NCT02949128: Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
Official title: Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-naïve Adult and Adolescent Patients 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: 2016-10-31
Enrollment: 58
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 safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement inhibitor.


Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 12 years of age and weighing ≥ 40 kg at the time of consent.
2. Evidence of thrombotic microangiopathy, 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, or at the time of, initiating study drug. Participants who received a meningococcal vaccine less than 2 weeks before initiating ravulizumab treatment must have received treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Participants who had not been vaccinated prior to initiating ravulizumab treatment should have received prophylactic antibiotics prior to and for at least 2 weeks after meningococcal vaccination. Participants \< 18 years of age must have been vaccinated against haemophilus influenzae type b and streptococcus pneumoniae according to national and local vaccination schedule guidelines.
4. Female participants of childbearing potential and male participants with female partners of childbearing potential had to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

Exclusion Criteria:

1. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency (activity \< 5%).
2. Shiga toxin-related hemolytic uremic syndrome.
3. Positive direct Coombs test.
4. Pregnancy or breastfeeding.
5. Identified drug exposure-related hemolytic uremic syndrome (HUS).
6. Bone marrow transplant/hematopoietic stem cell transplant within last 6 months prior to start of Screening.
7. HUS related to known genetic defects of cobalamin C metabolism.
8. 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).

Primary outcomes:
measure: Percentage Of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Time To Complete TMA Response
timeFrame: Baseline through Week 114
measure: Participants Who Do Not Require Dialysis at Weeks 26 and 52
timeFrame: Week 26 and Week 52
measure: Proportion Of Participants With Complete TMA Response At Week 52
timeFrame: Week 52
measure: Change From Baseline In Estimated Glomerular Filtration Rate (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 EuroQol 5-Dimension 3-Level (EQ-5D-3L) At Weeks 26 and 52
timeFrame: Baseline, Week 26 and 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 At Weeks 26 and 52
timeFrame: Baseline, Week 26 and Week 52
Other outcomes:
Locations:
city: Fort Wayne
country: United States
facility: Clinical Trial Site
state: Indiana
city: Fort Wayne
country: United States
facility: Clinical Trial Site
state: Indiana
city: Durham
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Columbus
country: United States
facility: Clinical Trial Site
state: Ohio
city: Clayton
country: Australia
facility: Clinical Trial Site
city: Geelong
country: Australia
facility: Clinical Trial Site
city: Parkville
country: Australia
facility: Clinical Trial Site
city: Vienna
country: Austria
facility: Clinical Trial Site
city: Brussels
country: Belgium
facility: Clinical Trial Site
city: London
country: Canada
facility: Clinical Trial Site
city: Bordeaux
country: France
facility: Clinical Trial Site
city: Clermont-Ferrand
country: France
facility: Clinical Trial Site
city: Lille
country: France
facility: Clinical Trial Site
city: Montpellier
country: France
facility: Clinical Trial Site
city: Nice
country: France
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Aachen
country: Germany
facility: Clinical Trial Site
city: Essen
country: Germany
facility: Clinical Trial Site
city: Hanover
country: Germany
facility: Clinical Trial Site
city: Muenchen
country: Germany
facility: Clinical Trial Site
city: Tuebingen
country: Germany
facility: Clinical Trial Site
city: Bologna
country: Italy
facility: Clinical Trial Site
city: Firenze
country: Italy
facility: Clinical Trial Site
city: Saitama
country: Japan
facility: Clinical Trial Site
city: Tokyo
country: Japan
facility: Clinical Trial Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Moscow
country: Russian Federation
facility: Clinical Trial Site
city: Saint Petersburg
country: Russian Federation
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Valencia
country: Spain
facility: Clinical Trial Site
city: Taichung
country: Taiwan
facility: Clinical Trial Site
city: Taipei City
country: Taiwan
facility: Clinical Trial Site
city: Taipei
country: Taiwan
facility: Clinical Trial Site
city: Cardiff
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
References:
citation: Barbour T, Scully M, Ariceta G, Cataland S, Garlo K, Heyne N, Luque Y, Menne J, Miyakawa Y, Yoon SS, Kavanagh D; 311 Study Group Members. Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults. Kidney Int Rep. 2021 Mar 24;6(6):1603-1613. doi: 10.1016/j.ekir.2021.03.884. eCollection 2021 Jun.
citation: Cammett TJ, Garlo K, Millman EE, Rice K, Toste CM, Faas SJ. Exploratory Prognostic Biomarkers of Complement-Mediated Thrombotic Microangiopathy (CM-TMA) in Adults with Atypical Hemolytic Uremic Syndrome (aHUS): Analysis of a Phase III Study of Ravulizumab. Mol Diagn Ther. 2023 Jan;27(1):61-74. doi: 10.1007/s40291-022-00620-3. Epub 2022 Nov 4.
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: Gackler A, Schonermarck U, Dobronravov V, La Manna G, Denker A, Liu P, Vinogradova M, Yoon SS, Praga M. Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis. BMC Nephrol. 2021 Jan 6;22(1):5. doi: 10.1186/s12882-020-02190-0.