A Study of Ravulizumab (ALXN1210) in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria

NCT03406507 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ALXN1210-PNH-3042017-002820-26
• Study Type: interventional
• Target: 13
• Locations: 6 countries
• Sites: 9

Brief Summary

The purpose of this study was to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ravulizumab in pediatric participants with paroxysmal nocturnal hemoglobinuria (PNH).

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

Ravulizumab; ALXN1210; Ultomiris; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Serum Concentration (Cmax) Of Ravulizumab

  Blood samples for determination of ravulizumab Cmax were collected before and after administration of study drug at designated time points. Results are reported in micrograms/milliliter (μg/mL).

  Week 1 (Day 1), Week 2 (Day 15), Week 10 (Day 71), and Week 18 (Day 127)

• Trough Serum Concentration (Ctrough) Of Ravulizumab

  Blood samples for determination of ravulizumab Ctrough were collected before and after administration of study drug at designated time points. Trough serum concentration was measured at end of dosing interval at steady state. Results are reported in μg/mL.

  Week 2 (Day 15), Week 10 (Day 71), Week 18 (Day 127), Week 26 (Day 183)

• Mean Accumulation Ratio For Cmax Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose

  Blood samples for determination of ravulizumab accumulation ratio for Cmax were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Cmax from the last maintenance dose (Week 18) divided by Cmax from the first maintenance dose (Week 2).

  Week 18

• Mean Accumulation Ratio For Ctrough Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose

  Blood samples for determination of ravulizumab accumulation ratio for Ctrough were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Ctrough from the last maintenance dose (Week 18) divided by Ctrough from the first maintenance dose (Week 2).

  Week 18

• Change In Free Complement Component C5 (C5) Concentrations Over Time

  Blood samples for determination of free C5 were collected before and after administration of study drug at designated time points.

  Baseline, Weeks 2, 10, 18, and 26 (end of infusion)

• Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time

  Blood samples for determination of cRBC hemolytic activity were collected before and after administration of study drug at designated time points.

  Baseline, Weeks 2, 10, 18, and 26

Secondary Outcomes (6)

• Percentage Change From Baseline At Week 26 In Lactate Dehydrogenase (LDH) Levels

  Baseline, Week 26

• Percentage Of Participants Who Achieved Transfusion Avoidance (TA)

  Week 26

• Change In Quality Of Life (QoL) From Baseline To Week 26

  Baseline, Week 26

• Percentage Of Participants With Stabilized Hemoglobin At Week 26

  Week 26

• Percentage Change In Free Hemoglobin From Baseline To Week 26

  Baseline, Week 26

Study Arms (1)

Ravulizumab

EXPERIMENTAL

Complement inhibitor treatment-naïve and eculizumab-experienced participants received ravulizumab.

Biological: Ravulizumab

Interventions

Ravulizumab BIOLOGICAL

Single intravenous (IV) loading dose on Day 1, followed by regular IV maintenance dosing beginning on Day 15, based on weight.

Also known as: ALXN1210, Ultomiris

Ravulizumab

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants from birth up to \<18 years of age and weighing ≥ 5 kilograms at the time of consent.
• PNH diagnosis confirmed by documented high-sensitivity flow cytometry.
• Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia, history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cell transfusion due to PNH.
• Lactate dehydrogenase (LDH) level ≥ 1.5 × upper limit of normal (ULN) for participants not being treated with eculizumab at screening and LDH level ≤ 1.5 × ULN for participants taking eculizumab.
• Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae.
• Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

You may not qualify if:

• History of bone marrow transplantation.
• History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.
• Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).
• Females who are pregnant or breastfeeding or who have a positive pregnancy test at screening or Day 1.
• Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (9)

Clinical Trial Site

Atlanta, Georgia, 30329, United States

Location

Clinical Trial Site

Milwaukee, Wisconsin, 53226, United States

Location

Clinical Trial Site

Paris, France

Location

Clinical Trial Site

Utrecht, Netherlands

Location

Clinical Trial Site

Oslo, Norway

Location

Clinical Trial Site

Moscow, Russia

Location

Clinical Trial Site

Saint Petersburg, Russia

Location

Clinical Trial Site

Leeds, United Kingdom

Location

Clinical Trial Site

London, United Kingdom

Location

Related Publications (2)

• Kulagin A, Chonat S, Maschan A, Bartels M, Buechner J, Punzalan R, Richards M, Ogawa M, Hicks E, Yu J, Baruchel A, Kulasekararaj AG. Pharmacokinetics, pharmacodynamics, efficacy, and safety of ravulizumab in children and adolescents with paroxysmal nocturnal hemoglobinuria: interim analysis of a phase 3, open-label study. Presented at the European Hematology Association 2021 Virtual Congress, June 9-17, 2021.

  RESULT

• Chonat S, Kulagin A, Maschan A, Bartels M, Buechner J, Punzalan R, Richards M, Ogawa M, Hicks E, Yu J, Baruchel A, Kulasekararaj AG. Pharmacokinetics, pharmacodynamics, efficacy, and safety of ravulizumab in pediatric paroxysmal nocturnal hemoglobinuria. Blood Adv. 2024 Jun 11;8(11):2813-2824. doi: 10.1182/bloodadvances.2023012267.

  PMID: 38551806 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

ravulizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

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

clinicaltrials@alexion.com

1.855.752.2356

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 23, 2018
• Study Start: February 22, 2018
• Primary Completion: March 25, 2020
• Study Completion: August 25, 2022
• Last Updated: March 27, 2023
• Results First Posted: May 9, 2022

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

GB (2); RU (2); FR (1); NO (1); NL (1); US (2)