Congenital Dyserythropoietic Anemia type II (CDAII) MedDRA version: 21.1 Level: PT Classification code 10081457 Term: Congenital dyserythropoietic anaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 21.1 Level: PT Classification code 10081457 Term: Congenital dyserythropoietic anaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
FOndazione per la Ricerca sulle ANemie ed EMoglobinopatie in ItaliA - For Anemia
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Males or female patients >= 18 years of age at the time of signing the informed consent document (ICF). - Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted. - Biallelic causative mutations in SEC23B gene alone or associated with other gene variants (e.g., globin gene defects). - Monoallelic causative mutations in SEC23B gene in presence of hypoglycosylation of band 3 and/or associated with other gene variants (e.g., globin gene defects). - Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 - Non-transfusion dependent (NTD) patients, defined as having received =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Any clinically significant pulmonary (including pulmonary hypertension), cardiovascular, endocrine, neurologic, hepatic (including cirrhosis and liver failure), gastrointestinal, infectious, immunological (including clinically significant allo- or auto-immunization) or genitourinary disease considered by the investigator as not adequately controlled prior to Cycle 1 Day 1. 2. Patients with history of cancer, or suffering from evolutive cancer, or in remission with treatment stopped less than 2 years before. 3. Anemia from other causes. 4. Symptomatic splenomegaly. 5. Thromboembolic events = grade 3 according to the National Cancer lnstitute-Common Terminology Criteria for Adverse Events (NCl-CTCAE) v.4 .0 (current active minor version) within 12 months prior to Cycle 1 Day 1. 6. Ejection fraction 450 msec on screening ECG. 9. Proteinuria = Grade 2. 10. Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1. 11. Treatment with another investigational drug or device, or approved therapy for investigational use 28 days prior to Cycle 1 Day 1, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer. 12. Transfusion event within 7 days prior to Cycle 1 Day 1. 13. Splenectomy within 56 days prior to Cycle 1 Day 1. 14. Major surgery (except splenectomy) within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1. 15. lron chelation therapy initiated within 56 days prior to Cycle 1 Day 1. 16. Cytotoxic agents, systemic corticosteroids, immunosuppressants, or anticoagulant therapy such as warfarin or heparin within 28 days prior to Cycle 1 Day 1 (prophylactic aspirin up to 100 mg/d is permitted). 17. Evidence of active hepatitis C (HCV) infection, or active infectious hepatitis B, or known positive human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - in transfusion dependent patients: the proportion of patients achieving any reduction of transfusion burden for at least 12 weeks during the treatment period; - in non-transfusion dependent patients: the proportion of subjects who achieve a mean hemoglobin increase by 1.0 g/dl sustained for 12 weeks within the first 24 weeks (in the absence of RBC transfusions).;Secondary Objective: Proportion of transfusion dependent subjects who achieve>=50%transfusion burden reduction over12and24weeks during treatment period as well duration of response Proportion of transfusion dependent subjects who achieve transfusion independency within 12 weeks and the duration of transfusion independence response up to week 48 Mean change in Hb level in NTD patients from baseline to week24 Main changes in biomarkers of erythropoiesis, markers of hemolysis, iron metabolism including Hepcidin and bone metabolism from baseline to Week 24 Mean change from baseline in LIC from baseline to Week48 Mean change from baseline in mean daily dose of ICT used Relative change (%) from baseline in serum ferritin level to Week 24 [serum levels were drawn at the baseline and at week 24. Levels were analyzed for serum ferritin measured in mg/L] Duration of reduction in transfusion burden or transfusion independence Duration of response in non-TD patients Ancillary studies on red cell before/after treatment;Primary end point(s): - in transfusion dependent patients: the proportion of patients achieving any reduction of transfusion burden for at least 12 weeks during the treatment period; - in non-transfusion dependent patients: the proportion of subjects who achieve a mean hemoglobin increase by 1.0 g/dl sustained for 12 weeks within the first 24 weeks (in the absence of RBC transfusions).;Timepoint(s) of evaluation of this end point: - in transfusion dependent patients at least 12 weeks during the treatment period - in non-transfusion dependent patients for 12 weeks within the first 24 wee | — |
Countries
Italy
Contacts
Public ContactTrial Center
FOndazione per la Ricerca sulle ANemie ed EMoglobinopatie in ItaliA - For Anemia
Outcome results
None listed