Clinical trial NCT03406507: A Study of Ravulizumab (ALXN1210) in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria
Official title: A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: Ravulizumab
ALXN1210
Ultomiris
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-01-23
Enrollment: 13
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) Of Ravulizumab
timeFrame: Week 1 (Day 1), Week 2 (Day 15), Week 10 (Day 71), and Week 18 (Day 127)
measure: Trough Serum Concentration (Ctrough) Of Ravulizumab
timeFrame: Week 2 (Day 15), Week 10 (Day 71), Week 18 (Day 127), Week 26 (Day 183)
measure: Mean Accumulation Ratio For Cmax Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose
timeFrame: Week 18
measure: Mean Accumulation Ratio For Ctrough Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose
timeFrame: Week 18
measure: Change In Free Complement Component C5 (C5) Concentrations Over Time
timeFrame: Baseline, Weeks 2, 10, 18, and 26 (end of infusion)
measure: Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time
timeFrame: Baseline, Weeks 2, 10, 18, and 26
Secondary outcomes:
measure: Percentage Change From Baseline At Week 26 In Lactate Dehydrogenase (LDH) Levels
timeFrame: Baseline, Week 26
measure: Percentage Of Participants Who Achieved Transfusion Avoidance (TA)
timeFrame: Week 26
measure: Change In Quality Of Life (QoL) From Baseline To Week 26
timeFrame: Baseline, Week 26
measure: Percentage Of Participants With Stabilized Hemoglobin At Week 26
timeFrame: Week 26
measure: Percentage Change In Free Hemoglobin From Baseline To Week 26
timeFrame: Baseline, Week 26
measure: Percentage Of Participants With Breakthrough Hemolysis (BTH) At Week 26
timeFrame: Week 26
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Clinical Trial Site
state: Georgia
city: Milwaukee
country: United States
facility: Clinical Trial Site
state: Wisconsin
city: Paris
country: France
facility: Clinical Trial Site
city: Utrecht
country: Netherlands
facility: Clinical Trial Site
city: Oslo
country: Norway
facility: Clinical Trial Site
city: Moscow
country: Russian Federation
facility: Clinical Trial Site
city: Saint Petersburg
country: Russian Federation
facility: Clinical Trial Site
city: Leeds
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
References:
citation: 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.