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

NCT03131219 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ALXN1210-aHUS-3122016-002499-29
• Study Type: interventional
• Target: 34
• Locations: 7 countries
• Sites: 18

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.

Conditions

Atypical Hemolytic Uremic Syndrome (aHUS)

Outcome Measures

Primary Outcomes (1)

• Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26

  Complete TMA response during the 26-week Initial Evaluation Period is a composite outcome measure that required normalization of hematological parameters (platelet count and lactate dehydrogenase \[LDH\]) and improvement in kidney function (≥25% reduction in serum creatinine from baseline); for participants on dialysis, baseline was established at least 6 days after the end of dialysis. Participants had to meet these criteria for 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. To be considered a responder during the 26-week Initial Evaluation Period, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment. Formal statistical comparison analyses were not planned for this study. Percentage based on the responders among treated participants. Confidence interval (CI) based on exact confidence limits using the Clopper Pearson method.

  Week 26

Secondary Outcomes (10)

• Time To Complete TMA Response In Complement Inhibitor Treatment-naïve Participants

  Baseline through at least Week 52 and up to Week 111

• Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52

  Week 52

• Participants Who Do Not Require Dialysis at Weeks 26 and 52

  Week 26 and Week 52

• Change From Baseline In eGFR At Weeks 26 and 52

  Baseline, Week 26 and Week 52

• Participants With Change From Baseline In CKD Stage At Weeks 26 and 52

  Baseline, Week 26, and Week 52

Study Arms (1)

Ravulizumab

EXPERIMENTAL

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.

Biological: Ravulizumab

Interventions

Ravulizumab BIOLOGICAL

Participant received weight-based dosages for 26 weeks during the Initial Evaluation Period. Participants received a loading dose on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter for participants weighing ≥ 20 kg, or once every 4 weeks for participant weighing \< 20 kg.

Also known as: ALXN1210, Ultomiris

Ravulizumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Complement Inhibitor Treatment Naïve:
• Participants from birth up to \<18 years of age and weighing ≥5 kilograms (kg) at the time of consent.
• Participants had not been previously treated with complement inhibitors.
• Evidence of thrombotic microangiopathy (TMA), including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
• Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
• 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:
• 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.
• Participants with documented diagnosis of aHUS.
• Participants with clinical evidence of response to eculizumab indicated by stable TMA parameters at screening.
• Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (18)

Research Site

Hollywood, Florida, 33021, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

Omaha, Nebraska, 68198, United States

Location

Research Site

Hackensack, New Jersey, 07601, United States

Location

Research Site

Charlotte, North Carolina, 28203, United States

Location

Research Site

Brussels, 1020, Belgium

Location

Research Site

Heidelberg, 69120, Germany

Location

Research Site

Milan, 20122, Italy

Location

Research Site

Jeju-do, 63241, South Korea

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Yangsan, 50612, South Korea

Location

Research Site

A Coruña, 15006, Spain

Location

Research Site

Barcelona, 8035, Spain

Location

Research Site

Esplugues de Llobregat, 8950, Spain

Location

Research Site

Valencia, 46026, Spain

Location

Research Site

Glasgow, G3 8SJ, United Kingdom

Location

Research Site

London, WC1N 3JH, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 32299680 RESULT

• Dixon BP, Kavanagh D, Aris ADM, Adams B, Kang HG, Wang E, Garlo K, Ogawa M, Amancha P, Chakravarty S, Heyne N, Kim SH, Cataland S, Yoon SS, Miyakawa Y, Luque Y, Muff-Luett M, Tanaka K, Greenbaum LA. Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials. Kidney Med. 2024 Jun 14;6(8):100855. doi: 10.1016/j.xkme.2024.100855. eCollection 2024 Aug.

  PMID: 39105067 DERIVED

• 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.

  PMID: 33783815 DERIVED

• 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.

  PMID: 33048203 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome

Interventions

ravulizumab

Condition Hierarchy (Ancestors)

Hemolytic-Uremic Syndrome; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2017
• First Posted: April 27, 2017
• Study Start: August 31, 2017
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: March 15, 2024
• Results First Posted: September 16, 2020

Record last verified: 2024-03

Locations

KR (3); IT (1); DE (1); ES (4); GB (2); BE (1); US (6)