This study compares the pharmacokinetics (PK) of ravulizumab subcutaneous (SC) administered via an on-body delivery system (OBDS) to ravulizumab intravenous (IV) in patients with paroxysmal nocturnal hemoglobinuria (PNH) currently treated With Eculizumab

• Register: EUCTR
• Last refreshed on: 9 October 2023
• Main ID: EUCTR2017-002370-39-SE
• Date of registration: 30/11/2018
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, Inc.
• Public title: This study compares the pharmacokinetics (PK) of ravulizumab subcutaneous (SC) administered via an on-body delivery system (OBDS) to ravulizumab intravenous (IV) in patients with paroxysmal nocturnal hemoglobinuria (PNH) currently treated With Eculizumab
• Scientific title: A Phase 3, Randomized, Parallel-Group, Multicenter, Open-Label, Pharmacokinetic, Noninferiority Study of Ravulizumab Administered Subcutaneously Versus Intravenously in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With Eculizumab
• Date of first enrolment: 27/03/2019
• Target sample size: 105
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002370-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Patients in the ravulizumab IV group will switch to 490 mg of ravulizumab SC in the extension period If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Ravulizumab iv Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Czechia, Finland, France, Germany, Italy, Korea, Republic of, Netherlands, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

Key inclusion & exclusion criteria

Inclusion criteria:
Age
1. Patients must be at least 18 years of age at the time of signing the informed consent.

Patient and Disease Characteristics
2. Treated with eculizumab according to the labeled dosing recommendation for PNH (900 mg every 14 days ± 2 days) for at least 3 months prior to study entry with no missed doses within 2 months prior to study entry and no more than 2 doses outside of the visit window.
3. Lactate dehydrogenase levels = 1.5 × ULN (upper limit of normal), according to central laboratory, at Screening. Sample must be obtained within 24 hours of or immediately prior to a scheduled eculizumab dose administration (ie, at trough eculizumab level).
4. Documented diagnosis of PNH confirmed by high-sensitivity flow cytometry evaluation (Borowitz, Craig et al. 2010).
5. Vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug to reduce the risk of meningococcal infection (N meningitidis).


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Medical Conditions
1. More than 1 LDH value > 2 × ULN within the 3 months prior to study entry.
2. Major adverse vascular event (MAVE) in the 6 months prior to study entry.
3. Platelet count < 30,000/mm3 (30 × 109/L) at Screening.
4. Absolute neutrophil count < 500/µL (0.5 × 109/L) at Screening.
5. History of bone marrow transplantation.
6. History of N meningitidis infection.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Paroxysmal Nocturnal Hemoglobinuria
MedDRA version: 21.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: Ravulizumab
Product Code: ALXN1210
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Ravulizumab
CAS Number: 1803171-55-2
Current Sponsor code: ALXN1210
Other descriptive name: Ravulizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-

Product Name: Ravulizumab
Product Code: ALXN1210
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ravulizumab
CAS Number: 1803171-55-2
Current Sponsor code: ALXN1210
Other descriptive name: Ravulizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 71

Main Objective: To evaluate PK noninferiority of ravulizumab SC
versus ravulizumab IV in adult patients with PNH

Primary end point(s): Day 71 serum ravulizumab Ctrough

Secondary Objective: - To characterize PK of ravulizumab SC
- To characterize PD of ravulizumab SC
- To characterize immunogenicity of ravulizumab SC
- To evaluate HRQoL and treatment satisfaction on ravulizumab SC
- To evaluate safety of ravulizumab SC and ravulizumab OBDS
- To evaluate efficacy of ravulizumab SC
- To assess performance of ravulizumab OBDS

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: throughout the study

Secondary end point(s): PK Endpoint
- Ctrough over time

PD Endpoint
- Free serum C5 concentrations over time

Immunogenicity Endpoint
- Incidence of treatment-emergent ADAs over time

HRQoL and Treatment Satisfaction Endpoints
- Change in FACIT-Fatigue Scale, Version 4, from Baseline to Day 183
- Change in EORTC QLQ-C30 Version 3.0, from Baseline to Day 183
- Reported treatment administration satisfaction as measured by the TASQ score at Baseline and Day 183
- Reported patient preference as measured by the PPQ-SC score at Days 1093

Safety Endpoints
- Change in physical examinations, vital signs, electrocardiograms, laboratory assessments over time
- Incidence of adverse events and serious adverse events
- Incidence of adverse device effects and serious adverse device effects

Efficacy Endpoints
- Change over time in LDH
- Incidence of breakthrough hemolysis
- Achievement of transfusion avoidance
- Achievement of stabilized hemoglobin
- Change in clinical manifestations of PNH over time
- Change in reticulocyte count over time
- Change in eGFR over time
- Change in PNH RBC clone size over time

Performance Endpoint
- Reported outcome of attempted full dose administration (including device failure/malfunction)

Secondary ID(s)

128367

2017-002370-39-DE

ALXN1210-PNH-303

Source(s) of Monetary Support

Alexion Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 27/03/2019
Contact:

Results

• Results available: Yes
• Date Posted: 25/08/2022
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-002370-39/results