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

A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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).

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.

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.