Research study investigating how well NDec works in people with sickle cell disease
- Conditions
- Sickle cell diseaseMedDRA version: 21.0Level: PTClassification code 10040644Term: Sickle cell diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-003485-39-GR
- Lead Sponsor
- ovo Nordisk A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 84
•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)
•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
•Reticulocyte count >1.5 x ULN at visit 1
•Body weight 40 to 125 kg (inclusive)
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 82
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
•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 10^9/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 is of child-bearing potential and not using highly effective methods of contraception (or adequate contraceptive measures as required by local regulation or practice) starting at screening and throughout the trial period and for 6 months after the last dose of trial product
•Male of reproductive age 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 (or adequate contraceptive measure as required by local regulation or practice) from trial start to:
oSix (6) months after the last dose of trial product for patients on NDec/Placebo
oSix (6) months after the last dose of trial product for patients outside US and CA randomised to HU
oTwelve (12) months after the last dose of trial product for patients randomised to HU in US and CA
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate the efficacy of two dosing regimens of oral decitabine-tetrahydrouridine (NDec) combination as measured by improvement in haemoglobin compared to placebo in hydroxyurea (HU)-non-eligible patients with sickle cell disease (SCD).;Secondary Objective: 1. To investigate the safety and tolerability of NDec in HU-non-active patients with SCD compared to placebo<br>2. To evaluate clinical efficacy measures of NDec in HU-non-active patients with SCD compared to placebo<br>3. To further describe the pharmacokinetics and pharmacodynamics of NDec in HU-non-active patients with SCD;Primary end point(s): Change in total haemoglobin;Timepoint(s) of evaluation of this end point: From baseline (week 0) to week 24
- Secondary Outcome Measures
Name Time Method Secondary end point(s): PK/PD endpoints:<br>1. Cmax for decitabine from pharmacokinetic assessment <br>2. Cmax for tetrahydrouridine from pharmacokinetic assessment<br>3. Change in DNMT1 activity<br>4. Change in CDA activity<br><br>Efficacy endpoints:<br>5. Change in foetal haemoglobin (g/dL)<br>6. Change in foetal haemoglobin as a proportion of total haemoglobin (%HbF)<br>7. Change in F-cell level as a proportion of total RBC (%F-cells)<br>8. Change in haemolysis measure: absolute reticulocyte count <br>9. Change in haemolysis measure: indirect bilirubin<br>10. Change in haemolysis measure: lactate dehydrogenase<br>11. Number of vaso-occlusive crises<br>12. Number of acute chest syndrome<br>13. Number of RBC units transfused<br><br>Safety endpoint:<br>14. Number of adverse events of grade 3 or higher;Timepoint(s) of evaluation of this end point: 1. & 2. At week 24<br>3. - 10. From baseline (week 0) to week 24<br>11. - 13. From baseline (week 0) to week 48<br>14. From baseline (week 0) to week 52