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: 30 April 2019
• Main ID: EUCTR2017-002370-39-FR
• Date of registration: 20/11/2018
• 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: 28/12/2018
• Target sample size: 105
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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, 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 6 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 6 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: 20.1 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: Fc- and CDR-modified humanised monoclonal antibody against C5
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: Fc- and CDR-modified humanised monoclonal antibody against C5
Current Sponsor code: ALXN1210
Other descriptive name: Ravulizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

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

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

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

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

HRQoL and Treatment Satisfaction Endpoints

Safety Endpoints

Efficacy Endpoints

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:
Contact: