NCT03474965

Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients

A Phase 2,Multicenter,Open-Label Study to Assess Appropriate Dosing and to Evaluate Safety of Crizanlizumab,With or Without Hydroxyurea/Hydroxycarbamide,in Sequential,Descending Age Groups of Pediatric Sickle Cell Disease Patients With Vaso-Occlusive Crisis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 117 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 2 Years – 17 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to confirm and to establish appropriate dosing and to evaluate the safety in pediatric participants ages 2 to \<18 years with a history of Vaso-Occlusive Crisis (VOC) with or without Hydroxyurea/Hydroxycarbamide (HU/HC), receiving crizanlizumab for 2 years. The efficacy and safety of crizanlizumab was previously demonstrated in adults with sickle cell disease. The approach was to extrapolate from the pharmacokinetics (PK)/pharmacodynamics (PD) already established in the adult population. The study was designed as a Phase II, multicenter, open-label study.

Detailed description

This was an open-label, single-arm study of crizanlizumab in sickle-cell disease (SCD) pediatric participants. This study consisted of 2 parts, Part A and Part B. In Part A, the dose for 3 age groups (see groups below), was first confirmed on the basis of single and multiple dose (steady state) PK data and key safety data from an initial subgroup of participants. In Part B, safety and efficacy were collected from additional participants from 6 to \<18 years (Groups 1 and 2, only). At least 100 participants were planned to be enrolled in the trial in total, split in 3 age groups: * Group 1 (age 12 to \<18 years): at least 26 participants (≥8 in Part A and ≥18 in Part B), * Group 2 (age 6 to \<12 years): at least 26 participants (≥8 in Part A and ≥18 in Part B), * Group 3 (age 2 to \<6 years): at least 8 participants (≥8 Part A). Crizanlizumab was administered every 4 weeks with a loading dose 2 weeks after the first dosing (i.e., by i.v. infusion) on Week 1 Day 1, Week 3 Day 1, and then day 1 of every fourth week) for up to 2 years. The initial dose of crizanlizumab was 5 mg/kg dose for Group 1 and Group 2 Part A. It was later adjusted to 8.5 mg/kg for Group 2 and 3 based on final dose confirmation from emerging PK data analysis and safety considerations determined in Part A of the study.

Conditions

• Sickle Cell Disease (SCD)

Interventions

Type	Name	Description
DRUG	Crizanlizumab	Crizanlizumab (SEG101) is a concentrate for solution for infusion, i.v. use. Supplied in single use 10 mL vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab.

Timeline

• Start date: 2018-10-01
• Primary completion: 2024-11-06
• Completion: 2024-11-06
• First posted: 2018-03-23
• Last updated: 2025-10-16
• Results posted: 2025-07-20

Locations

35 sites across 14 countries: United States, Belgium, Brazil, Canada, Colombia, France, Germany, India, Italy, Lebanon, Oman, Spain, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study