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

NCT ID: NCT03406507

Last Updated: 2023-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-22
• Study Completion Date: 2022-08-25

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).

Detailed Description

The study consists of a 4-week Screening Period, a 26-week Primary Evaluation Period, and an Extension Period of up to 4 years (with the exception of any country-specific mandates), whichever occurs first.

Efficacy and safety data are reported for the 26-week Primary Evaluation Period only. Analyses were conducted separately for complement inhibitor treatment-naïve participants and eculizumab-experienced participants.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ravulizumab

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

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: BIOLOGICAL

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

Interventions

Ravulizumab

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

Intervention Type: BIOLOGICAL

Other Intervention Names

ALXN1210; Ultomiris

Eligibility Criteria

Inclusion Criteria

1. Participants from birth up to <18 years of age and weighing ≥ 5 kilograms at the time of consent.

2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry.

3. 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.

4. 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.

5. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae.

6. 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.

Exclusion Criteria

1. History of bone marrow transplantation.

2. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.

3. 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).

4. Females who are pregnant or breastfeeding or who have a positive pregnancy test at screening or Day 1.

5. 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.

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Trial Site

Atlanta, Georgia, United States

Clinical Trial Site

Milwaukee, Wisconsin, United States

Clinical Trial Site

Paris, , France

Clinical Trial Site

Utrecht, , Netherlands

Clinical Trial Site

Oslo, , Norway

Clinical Trial Site

Moscow, , Russia

Clinical Trial Site

Saint Petersburg, , Russia

Clinical Trial Site

Leeds, , United Kingdom

Clinical Trial Site

London, , United Kingdom

Countries

United States; France; Netherlands; Norway; Russia; United Kingdom

References

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.

Reference Type: 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.

Reference Type: DERIVED

PMID: 38551806 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-002820-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALXN1210-PNH-304

Identifier Type: -

Identifier Source: org_study_id