Patients with Sickle Cell Disease. Sickle cell disease (SCD) Foetal haemoglobin (HbF) mutated sickle cell haemoglobin (HbS)
Conditions
Interventions
Patients will be receiving a new medication oral decitabinetetrahydrouridine (NDec).
NDec once weekly: 1 dose of active treatment and 1 dose of placebo on 2 consecutive days ? NDec twice weekly: 1 dose of active treatment on each of 2 consecutive days ? Placebo: 1 dose of placebo on e
decitabine-tetrahydrouridine (NDec) Placebo
hydroxyurea HU
Sponsors
Novo Nordisk
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Key inclusion criteria: - Age above or equal to 18 years at the time of signing informed consent - Confirmed diagnosis of SCD (including HbSS, HbSC, HbSß0 thalassaemia and HbSß+ thalassaemia or other Sickle Cell disease variants) - 2–10 episodes of documented VOCs within the last 12 months prior to the screening visit - Haemoglobin =5.0 g/dL and =10.5 g/dL at visit 1 - Absolute reticulocyte (absolute) count above ULN at visit 1 - Body weight 40 to 125 kg (inclusive)
Exclusion criteria
Exclusion criteria: Key exclusion criteria: - Patient is on chronic transfusion therapy as defined by receiving scheduled (pre-planned) series of blood transfusion (simple or exchange) for prophylactic purposes, or the patient is likely to begin chronic transfusion therapy during the course of the trial, or has received RBC or whole blood transfusion for any reason within 28 days of visit 1 - Receipt of erythropoietin or other haematopoietic growth factor treatment within 28 days of signing ICF, or planned treatment with these agents during the trial - Receipt of voxelotor, crizanlizumab or L-glutamine treatment within 12 weeks of signing the informed consent form, or planned treatment with such agents during the trial - Platelet count >800 x 109/L at visit 1 - Absolute neutrophil count =1.5 x 109/L at visit 1 - Any condition/concurrent chronic disease involving the stomach or small intestine which may affect drug absorption, as per investigator's judgement - Female who is: - pregnant, breast-feeding or intends to become pregnant within 6 months after the final trial product administration or - child-bearing potential and not using highly effective methods of contraception and whose male partner is not using effective contraception, at screening and until 6 months after the last dose of trial product - Male with female partner of childbearing potential who does not agree to use condom and whose female partner of childbearing potential is not using a highly effective contraceptive measure from trial start to: - Six (6) months after the last dose of trial product for patients on NDec/Placebo - Six (6) months after the last dose of trial product for patients outside US and CA randomised to HU - Twelve (12) months after the last dose of trial product for patients randomised to HU in US and CA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: Change in total haemoglobin;Timepoints: From baseline (week 0) to week 24;Measure: g/dL | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: Cmax for decitabine from pharmacokinetic assessment;Timepoints: At week 24;Measure: ng/mL;Name: Cmax for tetrahydrouridine from pharmacokinetic assessment;Timepoints: At week 24;Measure: ng/mL;Name: Change in DNMT1 activity;Timepoints: From baseline (week 0) to week 24;Measure: MFI;Name: Change in CDA activity;Timepoints: From baseline (week 0) to week 24;Measure: µmol/L/min;Name: Change in foetal haemoglobin (g/dL);Timepoints: From baseline (week 0) to week 24;Measure: g/dL;Name: Number of adverse events of?grade 3b or higher;Timepoints: From baseline (week 0) to week 52;Measure: Number of events | — |
Countries
Canada, France, Greece, India, Italy, Lebanon, South Africa, Spain, Turkey, United Kingdom, United States of America
Contacts
Public ContactBadiaa Masri
Novo Nordisk Pharma SARL
Outcome results
None listed