Research Study Investigating How Well NDec Works in People With Sickle Cell Disease (ASCENT1)

A Multicentre Trial Evaluating the Efficacy and Safety of Oral Decitabine Tetrahydrouridine (NDec) in Patients With Sickle Cell Disease

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: NDec - oral decitabine-tetrahydrouridine; Drug: Placebo; Drug: HU - Hydroxyurea

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, ON N6A 5W9
      • LHSC - Victoria Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital, Liver Clinic
    • Toronto, Ontario, Canada, M5G2C4
      • Toronto General Hospital, Liver Clinic
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• France
  • Grenoble, France, 38043
    • Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-3
  • Lyon, France, 69437
    • Hospices Civils de Lyon-Hopital Edouard Herriot
• Greece
  • Goudi, Greece, 11527
    • Aghia Sophia Childrens' Hospital
  • Larissa, Greece, 41221
    • General Hospital Of Larissa Koutlibaneio And Triantafylleio - Thalassemia and SCD Unit
  • Pátrai, Greece, 26504
    • Gen Univ Hospital of Patras, Thalassemia/Hemoglobinopathies
• India
  • Nagpur, India, 440001
    • KIMS - Kingsway Hospital
  • Chhattisgarh
    • Raipur, Chhattisgarh, India, 492099
      • All India Institute of Medical Sciences (AIIMS), Raipur
  • Gujarat
    • Surat, Gujarat, India, 395002
      • Nirmal Hospital Pvt. Ltd.
    • Surat, Gujarat, India, 395009
      • BAPS Pramukh Swami Hospital
    • Vadodara, Gujarat, India, 390006
      • SSG Hospital, Baroda
    • Vadodara, Gujarat, India, 390001
      • SSG Hospital, Baroda
  • Karnataka
    • Bangalore, Karnataka, India, 560002
      • Victoria Hospital (Bangalore Medical College and Research Institute)
    • Mysore, Karnataka, India, 570004
      • J.S.S.Hospital
  • Kerala
    • Kozhikode, Kerala, India, 673008
      • Government Medical College, Kozhikode
  • Maharashtra
    • Mumbai, Maharashtra, India, 400022
      • K.J Somaiya Hospital and Research Centre
    • Nagpur, Maharashtra, India, 440003
      • Government Medical College and Hospital
    • Nagpur, Maharashtra, India, 440003
      • Government Medical College and Super Speciality Hospital, Nagpur
    • Nagpur, Maharashtra, India, 440009
      • Government Medical College and Super Speciality Hospital, Nagpur
  • Odisha
    • Bhubaneswar, Odisha, India, 751003
      • IMS and SUM Hospital
    • Cuttack, Odisha, India, 753007
      • S.C.B. Medical College
  • Tamil Nadu
    • Ranipet, Tamil Nadu, India, 632517
      • Christian Medical College Hospital, Vellore
    • Vellore, Tamil Nadu, India, 632004
      • Christian Medical College Hospital, Vellore
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Yashoda Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Sanjay Gandhi Postgraduate Institute of Medical Sciences
  • West Bengal
    • Kolkata, West Bengal, India, 700014
      • NRS Medical College & Hospital
    • Kolkata, West Bengal, India, 70014
      • NRS Medical College & Hospital
• Italy
  • Genova, Italy, 16128
    • Ospedali Galliera
  • Milan, Italy, 20122
    • Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
  • Padua, Italy, 35128
    • Azienda Ospedale Universita Padova
  • Verona, Italy, 37134
    • Policlinico GB Rossi
  • Verona, Italy, 37134
    • Azienda Ospedaliera Universitaria Integrata Verona Policlinico GB Rossi - Borgo Roma
• Lebanon
  • Tripoli, Lebanon, 1434
    • Hospital Nini
• Oman
  • Muscat, Oman, 123
    • Sultan Qaboos University Hospital
• South Africa
  • Gauteng
    • Parktown, Johannesburg, Gauteng, South Africa, 2193
      • Charlotte Maxeke Johannesburg Academic Hospital
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Acıbadem Adana Hastanesi-Hematoloji
  • Adana, Turkey (Türkiye), 01130
    • Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Üniversitesi Hastanesi- Hematoloji
  • Mersin, Turkey (Türkiye), 33110
    • Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, NW10 7NS
    • Central Middlesex Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hosptial
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
• United States
  • Alabama
    • Mobile, Alabama, United States, 36617
      • University of South Alabama
  • California
    • Oakland, California, United States, 94609
      • UCSF Oakland Benioff Children's Hospital
    • Orange, California, United States, 92868
      • Center for Inherited Blood Dis
    • Torrance, California, United States, 90502-2004
      • Harbor-UCLA Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical and Transl Res Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20060
      • Howard University
  • Florida
    • Hollywood, Florida, United States, 33023
      • Foundation for Sickle Cell Disease Research
    • Miami, Florida, United States, 33136
      • University of Miami Hospital & Clinics
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Louisiana
    • Metairie, Louisiana, United States, 70002
      • Tulane Sickle Cell Ctr- So LA
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Mississippi Center Advanced Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Cure 4 the Kids Foundation
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • The Bronx, New York, United States, 10461
      • Jacobi Medical Center
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina Univ-Greenville
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center_Oklahoma City
    • Oklahoma City, Oklahoma, United States, 73104
      • Univ Oklahoma HSC_Okla City
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • St Christopher Hosp for Child
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical Univ of SC Charleston
  • Texas
    • Houston, Texas, United States, 77030
      • Univ Texas HSC-Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HU-non-eligible - NDec plus placebo; HU-non eligible patients randomised to treatment with NDec on one day and placebo on the other day	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; HU-non eligible patients randomised to treatment with NDec on both days	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; HU-non eligible patients randomised to treatment with placebo on both days	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; HU-active patients randomised to treatment with NDec on one day and placebo on the other day	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; HU-active patients randomised to treatment with NDec on both days	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; HU-active patients randomised to continue on open-label HU treatment	Drug: HU - Hydroxyurea; Participants will get capsules daily (oral administration) according to local labelling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total haemoglobin	measured in g/dL	From baseline (week 0) to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax for decitabine from pharmacokinetic assessment	measured in ng/mL	At week 24
Cmax for tetrahydrouridine from pharmacokinetic assessment	measured in ng/mL	At week 24
Change in DNA methyltransferase 1 (DNMT1) activity	measured in MFI units	From baseline (week 0) to week 24
Change in cytidine deaminase (CDA) activity	µmol/L/min	From baseline (week 0) to week 24
Change in foetal haemoglobin (g/dL)	measured in g/dL	From baseline (week 0) to week 24
Change in foetal haemoglobin as a proportion of total haemoglobin (%HbF)	measured in %	From baseline (week 0) to week 24
Change in F-cell level as a proportion of total red blood cell (RBC) (%F-cells)	measured in %	From baseline (week 0) to week 24
Change in haemolysis measure: absolute reticulocyte count	measured in cells × 10^9/L	From baseline (week 0) to week 24
Change in haemolysis measure: indirect bilirubin	measured in mg/dL	From baseline (week 0) to week 24
Change in haemolysis measure: lactate dehydrogenase	measured in U/L	From baseline (week 0) to week 24
Number of vaso-occlusive crises	number of events	From baseline (week 0) to week 48
Number of acute chest syndrome	number of events	From baseline (week 0) to week 48
Number of RBC units transfused	measured in Units	From baseline (week 0) to week 48
Number of adverse events of grade 3 or higher	number of events	From baseline (week 0) to week 52

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Publications and helpful links

General Publications

• Abbasi M, Srivastava A, Saraf SL. Management of Kidney Disease with Sickle Cell Disease. J Am Soc Nephrol. 2025 Oct 1;36(10):2041-2054. doi: 10.1681/ASN.0000000804. Epub 2025 Jun 26.
• Helleberg H, Bjornsdottir I, Offenberg HK. Effects of Tetrahydrouridine Pre-dosing on Absorption, Metabolism, and Excretion of Decitabine in the Mouse. Eur J Pharm Sci. 2025 Oct 27;216:107353. doi: 10.1016/j.ejps.2025.107353. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2022
• Primary Completion (Actual): July 24, 2025
• Study Completion (Actual): July 24, 2025

Study Registration Dates

• First Submitted: May 31, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: NN7533-4470; U1111-1255-1324 (Other Identifier: World Health Organization (WHO)); 2020-003485-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: "According to the Novo Nordisk disclosure commitment on novonordisk-trials.com"

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No