Paroxysmal nocturnal hemoglobinuria (PNH) that is treated with either eculizumab or ravulizumab as per local label MedDRA version: 21.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857
Conditions
Interventions
Trade Name: Soliris 300
Product Name: ECULIZUMAB
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ECULIZUMAB
CAS Number: 219685-50-4
Concentration unit: mg/ml milligram(
Sponsors
Roche Farma S. A. U. que realiza el ensayo en España y que actua como representante F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 12 years - Willingness and ability to comply with all the study visits and procedures - Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry evaluation of RBCs with granulocyte or monocyte clone size of = 10%, within 6 months prior to study enrollment - Documented treatment with eculizumab or ravulizumab with dose and frequency according to local label for PNH * Patients treated with eculizumab must have received a stable eculizumab dose for at least 4 months prior to study enrollment - LDH level = 2 × upper limit of normal (ULN) at screening - Vaccination against Neisseria meningitidis 200 cells/µL and they meet all other criteria - Adequate hepatic and renal function, at screening Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 134 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: - Major adverse vascular event within 6 months prior to study enrollment - Platelet count 5 years prior to study enrollment are eligible * Patients with curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to study enrollment are eligible * Patients with low-grade, early-stage prostate cancer with no requirement for therapy at any time prior to study enrollment are eligible - History of ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or Sponsor, precludes the patient’s participation in an investigational clinical trial - Unstable medical conditions (e.g., myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 12 months of study enrollment, coexisting chronic anemia unrelated to PNH) that would make the patient unlikely to tolerate the requirements of the interventional study on crovalimab - History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in eculizumab or ravulizumab or crovalimab, including hypersensitivity to human, humanized, or murine monoclonal antibodies or known hypersensitivity to any constituent of the product - Pregnancy or breastfeeding, or intention of becoming pregnant during the study - Participation in another interventional treatment study or use of any experimental therapy within 30 days or within 5 half-lives of that investigational product prior to study enrollment, with the following exception: Patients enrolled in an eculizumab or ravulizumab interventional study are eligible provided they fulfill eligibility (e.g., are willing and able to comply with the study assessments) - Known medical or psychological condition or risk factor that, in the opinion of the investigator, might interfere with the patient’s participation in this study, pose any additional risk for the patient, or confound the assessment of the patient or outcome of this study and the interventional study of crovalimab - Known or suspected hereditary complement deficiency - Treatment with azathioprine or erythrocyte-stimulating agents within 14 days prior to study enrollment - Splenectomy < 6 months prior to study enrollment - Diagnosis of auto-immune connective tissue diseases - Any evidence of active inflammatory conditions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To document the efficacy of standard of care (SOC) treatment with eculizumab on the basis of lactate dehydrogenase (LDH) levels over time under routine clinical practice;Secondary Objective: - To document the efficacy of ravulizumab on the basis of LDH levels over time under routine clinical practice - To document the efficacy (inclusive of health-related quality of life [HRQoL]), safety, pharmacokinetics, pharmacodynamics (PD), treatment satisfaction, and health status of SOC treatment with eculizumab or treatment with ravulizumab on the basis ofoccurrence of breakthrough hemolysis, number of blood transfusions, units of packed red blood cells transfused, hemoglobin and haptoglobin levels over time, serum concentration and HRQoL assessed by Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) questionnaire, Euro Quality of life 5-Dimension Questionnaire (5-level version; EQ-5D-5L) index-based and visual analog scale scores - To evaluate the safety on basis of incidence and severity of adverse events - To evaluate PD biomarkers;Primary end point(s): 1. Document LDH levels over time under routine clinical practice with eculizumab treatment;Timepoint(s) of evaluation of this end point: 1. Day 1, 29, 57, 85, 113, 141,169, 197, 225, 253, 281 (Q4W [every 4 weeks]) beyond and at treatment discontinuation (TD) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Document LDH levels over time under routine clinical practice with ravulizumab 2. Document occurrence of breakthrough hemolysis (BTH) 3. Document the number of units of packed red blood cells transfused 4. Document the number of blood transfusions 5. Document hemoglobin and haptoglobin levels over time 6. Document serum concentration of eculizumab or ravulizumab 7. Health -related quality of life as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue, selected scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Questionnaire-Core-30, and selected PNH-relevant symptoms from the EORTC Item Library 8. Health status as assessed by the Euro Quality of life 5-Dimension Questionnaire (5-level version; EQ-5D-5L) index-based and visual analog scale scores 9. Information on treatment satisfaction as assessed by the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) questionnaire in adult patients with PNH 10. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 11. Pharmacodynamic biomarkers;Timepoint(s) of evaluation of this end point: 1. Day 1,57,113,169,225,281 (Q8W) beyond and at TD 2-4. Eculizumab cohort (EC): Day 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225, 239, 253, 267, 281 (Q2W) beyond; Ravulizumab cohort (RC): Day 1, 57, 113, 169, 225, 281 (Q8W) beyond and at TD 5-6. EC: Day 1, 29, 57, 85, 113, 141,169, 197, 225, 253, 281 (Q4W) beyond and at TD; RC: Day 1, 57, 113, 169, 225, 281 (Q8W) beyond and at TD 7-8. EC: Day 1,57,113,169,225,281 (Q8W) beyond and at TD; RC: Day 1,57,113,169,225,281 (Q8W) beyond and at TD 9. EC and RC: Day 113 10. Until the study completion 11. For PNH clone size and C3d only: EC: Day 1, 71 and at TD; RC: Day 1, 57 and at TD Others: for EC day 1, 29, 57, 71, 85, 113, 141,169, 197, 225, 253, (Q4W) be | — |
Countries
Argentina, Brazil, Canada, Colombia, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed