ASCENT1: Research Study Investigating How Well NDec Works in People With Sickle Cell Disease
Study Details
Study Description
Brief Summary
This study will look at how well a potentially new medicine called NDec works and is tolerated in people with sickle cell disease. NDec is a combination of two medicines (decitabine-tetrahydrouridine). Both medicines are new for the treatment of sickle cell disease,
Participants will either get NDec, placebo or continue on Hydroxyurea (HU) - which treatment participants get is decided by chance. If participants get NDec or the placebo, they will get capsules to take twice weekly.
The study will last for about a year.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HU-non-eligible - NDec plus placebo For patients randomised to NDec once weekly, NDec twice weekly or placebo, trial products are administered to all patients on 2 consecutive days every week regardless of randomised treatment. |
Drug: NDec - oral decitabine-tetrahydrouridine
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
Drug: Placebo
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
|
| Experimental: HU-non-eligible - NDec plus NDec For patients randomised to NDec once weekly, NDec twice weekly or placebo, trial products are administered to all patients on 2 consecutive days every week regardless of randomised treatment. |
Drug: NDec - oral decitabine-tetrahydrouridine
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
|
| Placebo Comparator: HU-non-eligible - Placebo plus placebo For patients randomised to NDec once weekly, NDec twice weekly or placebo, trial products are administered to all patients on 2 consecutive days every week regardless of randomised treatment. |
Drug: Placebo
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
|
| Experimental: HU-active - NDec plus placebo For patients randomised to NDec once weekly, NDec twice weekly or placebo, trial products are administered to all patients on 2 consecutive days every week regardless of randomised treatment. |
Drug: NDec - oral decitabine-tetrahydrouridine
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
Drug: Placebo
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
|
| Experimental: HU-active - NDec plus NDec For patients randomised to NDec once weekly, NDec twice weekly or placebo, trial products are administered to all patients on 2 consecutive days every week regardless of randomised treatment. |
Drug: NDec - oral decitabine-tetrahydrouridine
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
|
| Active Comparator: HU-active - HU Patients randomised to open-label HU treatment will continue on HU treatment. |
Drug: HU - Hydroxyurea
Participants will get capsules daily (oral administration) according to local labelling
|
Outcome Measures
Primary Outcome Measures
- Change in total haemoglobin [From baseline (week 0) to week 24]
measured in g/dL
Secondary Outcome Measures
- Cmax for decitabine from pharmacokinetic assessment [At week 24]
measured in ng/mL
- Cmax for tetrahydrouridine from pharmacokinetic assessment [At week 24]
measured in ng/mL
- Change in DNA methyltransferase 1 (DNMT1) activity [From baseline (week 0) to week 24]
measured in MFI units
- Change in cytidine deaminase (CDA) activity [From baseline (week 0) to week 24]
µmol/L/min
- Change in foetal haemoglobin (g/dL) [From baseline (week 0) to week 24]
measured in g/dL
- Change in foetal haemoglobin as a proportion of total haemoglobin (%HbF) [From baseline (week 0) to week 24]
measured in %
- Change in F-cell level as a proportion of total red blood cell (RBC) (%F-cells) [From baseline (week 0) to week 24]
measured in %
- Change in haemolysis measure: absolute reticulocyte count [From baseline (week 0) to week 24]
measured in cells × 10^9/L
- Change in haemolysis measure: indirect bilirubin [From baseline (week 0) to week 24]
measured in mg/dL
- Change in haemolysis measure: lactate dehydrogenase [From baseline (week 0) to week 24]
measured in U/L
- Number of vaso-occlusive crises [From baseline (week 0) to week 48]
number of events
- Number of acute chest syndrome [From baseline (week 0) to week 48]
number of events
- Number of RBC units transfused [From baseline (week 0) to week 48]
measured in Units
- Number of adverse events of grade 3 or higher [From baseline (week 0) to week 52]
number of events
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age above or equal to 18 years at the time of signing informed consent
-
Confirmed diagnosis of SCD (including HbSS, HbSC, HbSβ0 thalassaemia and HbSβ+ thalassaemia)
-
2-10 episodes of documented vaso-occlusive crisis (VOCs) within the last 12 months prior to the screening visit
-
Haemoglobin greather than or equal to 5.0 g/dL and below or equal to 10.5 g/dL at visit 1
-
Reticulocyte count greater than1.5 x upper limit of the normal (ULN) at visit 1
-
Body weight 40 to 125 kg (inclusive)
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 greater than 800 x 10^9/L at visit 1
-
Absolute neutrophil count below1.5 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:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Adana | Turkey | 01130 | |
| 2 | Novo Nordisk Investigational Site | Mersin | Turkey | 33110 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NN7533-4470
- U1111-1255-1324
- 2020-003485-39