Research Study Investigating How Well NDec Works in People With Sickle Cell Disease

Phase 2

Active, not recruiting

• Conditions: Sickle Cell Disease
• Interventions: Drug: NDec - oral decitabine-tetrahydrouridine; Drug: HU - Hydroxyurea; Drug: Placebo

• Registration Number: NCT05405114
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This study examines how well a new, potential 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 who are not taking Hydroxyurea (HU) will get NDec, NDec and placebo, or placebo. Participants who are on HU treatment before joining the study will get NDec, NDec and placebo, or continue on HU. Which treatment participants get is decided by chance. Participants getting NDec and/or Placebo will get capsules to take twice weekly. The study will last for about a year.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-31
• Study First Submitted QC: 2022-05-31
• Study First Posted: 2022-06-06
• Study Start: 2022-07-07
• Status Verified: 2025-08
• Primary Completion: 2025-08-27
• Study Completion: 2025-08-27
• Last Update Submitted: 2025-08-28
• Last Update Posted: 2025-08-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 84

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 or other Sickle Cell disease variants)
• 2-10 episodes of documented vaso-occlusive crisis (VOCs) within the last 12 months prior to the screening visit
• Haemoglobin greater than or equal to 5.0 g/dL and below or equal to 10.5 g/dL at visit 1
• Absolute reticulocyte count above 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 below or equal to 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
  • 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HU-non-eligible - NDec plus placebo	NDec - oral decitabine-tetrahydrouridine	HU-non eligible patients randomised to treatment with NDec on one day and placebo on the other day
HU-non-eligible - NDec plus placebo	Placebo	HU-non eligible patients randomised to treatment with NDec on one day and placebo on the other day
HU-non-eligible - NDec plus NDec	NDec - oral decitabine-tetrahydrouridine	HU-non eligible patients randomised to treatment with NDec on both days
HU-non-eligible - Placebo plus placebo	Placebo	HU-non eligible patients randomised to treatment with placebo on both days
HU-active - NDec plus placebo	NDec - oral decitabine-tetrahydrouridine	HU-active patients randomised to treatment with NDec on one day and placebo on the other day
HU-active - NDec plus placebo	Placebo	HU-active patients randomised to treatment with NDec on one day and placebo on the other day
HU-active - NDec plus NDec	NDec - oral decitabine-tetrahydrouridine	HU-active patients randomised to treatment with NDec on both days
HU-active - HU	HU - Hydroxyurea	HU-active patients randomised to continue on open-label HU treatment

Primary Outcome Measures

Name	Time	Method
Change in total haemoglobin	From baseline (week 0) to week 24	measured in g/dL

Secondary Outcome Measures

Name	Time	Method
Cmax for tetrahydrouridine from pharmacokinetic assessment	At week 24	measured in ng/mL
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 %
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
Change in DNA methyltransferase 1 (DNMT1) activity	From baseline (week 0) to week 24	measured in MFI units
Cmax for decitabine from pharmacokinetic assessment	At week 24	measured in ng/mL
Change in cytidine deaminase (CDA) activity	From baseline (week 0) to week 24	µmol/L/min
Change in haemolysis measure: lactate dehydrogenase	From baseline (week 0) to week 24	measured in U/L
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

Trial Locations

Locations (44)

UCSF Oakland Benioff Children's Hospital; 🇺🇸 Oakland, California, United States

Harbor-UCLA Medical Center; 🇺🇸 Torrance, California, United States

Clinical and Transl Res Center; 🇺🇸 Aurora, Colorado, United States

University Of Illinois at Chicago; 🇺🇸 Chicago, Illinois, United States

Mississippi Center Advanced Medicine; 🇺🇸 Madison, Mississippi, United States

Cure 4 the Kids Foundation; 🇺🇸 Las Vegas, Nevada, United States

Mount Sinai School of Medicine; 🇺🇸 New York, New York, United States

University of Oklahoma Health Sciences Center_Oklahoma City; 🇺🇸 Oklahoma City, Oklahoma, United States

St Christopher Hosp for Child; 🇺🇸 Philadelphia, Pennsylvania, United States

Univ Texas HSC-Houston; 🇺🇸 Houston, Texas, United States

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