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
3 other identifiers
interventional
96
14 countries
118
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2022
Typical duration for phase_2
118 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 31, 2022
CompletedFirst Posted
Study publicly available on registry
June 6, 2022
CompletedStudy Start
First participant enrolled
July 7, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 24, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 24, 2025
CompletedJuly 22, 2026
July 1, 2026
3 years
May 31, 2022
July 21, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Change in total haemoglobin
measured in g/dL
From baseline (week 0) to week 24
Secondary Outcomes (14)
Cmax for decitabine from pharmacokinetic assessment
At week 24
Cmax for tetrahydrouridine from pharmacokinetic assessment
At week 24
Change in DNA methyltransferase 1 (DNMT1) activity
From baseline (week 0) to week 24
Change in cytidine deaminase (CDA) activity
From baseline (week 0) to week 24
Change in foetal haemoglobin (g/dL)
From baseline (week 0) to week 24
- +9 more secondary outcomes
Study Arms (6)
HU-non-eligible - NDec plus placebo
EXPERIMENTALHU-non eligible patients randomised to treatment with NDec on one day and placebo on the other day
HU-non-eligible - NDec plus NDec
EXPERIMENTALHU-non eligible patients randomised to treatment with NDec on both days
HU-non-eligible - Placebo plus placebo
PLACEBO COMPARATORHU-non eligible patients randomised to treatment with placebo on both days
HU-active - NDec plus placebo
EXPERIMENTALHU-active patients randomised to treatment with NDec on one day and placebo on the other day
HU-active - NDec plus NDec
EXPERIMENTALHU-active patients randomised to treatment with NDec on both days
HU-active - HU
ACTIVE COMPARATORHU-active patients randomised to continue on open-label HU treatment
Interventions
Participants will get capsules daily (oral administration) according to local labelling
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight
Eligibility Criteria
You may qualify if:
- 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)
- 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).
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novo Nordisk A/Slead
Study Sites (118)
University Of South Alabama
Mobile, Alabama, 36617, United States
Keck Medical Center of USC - Outpatient Clinic
Los Angeles, California, 90033, United States
UCSF Oakland Benioff ChildHosp
Oakland, California, 94609, United States
Center for Inherited Blood Dis
Orange, California, 92868, United States
Harbor-UCLA Medical Center
Torrance, California, 90502-2004, United States
Clinical and Transl Res Center
Aurora, Colorado, 80045, United States
Carole&Ray Neag Comp S.C. Ctr
Farmington, Connecticut, 06030, United States
Tova Community Health Inc
Wilmington, Delaware, 19805, United States
Howard University Hospital Department Med
Washington D.C., District of Columbia, 20060, United States
Howard University
Washington D.C., District of Columbia, 20060, United States
Foundation for Sickle Cell Disease Research
Hollywood, Florida, 33023, United States
University of Florida, College of Medicine Jacksonville
Jacksonville, Florida, 32209, United States
University of Miami Hospital & Clinics
Miami, Florida, 33136, United States
Emory University School Of Med
Atlanta, Georgia, 30333, United States
Aflac Cancer/Blood Dis CCH
Atlanta, Georgia, 30342, United States
Emory University School Of Med
Atlanta, Georgia, 30342, United States
Augusta University
Augusta, Georgia, 30912, United States
Rush University Med. Cntr
Chicago, Illinois, 60612, United States
Univer Of Illinois at Chicago
Chicago, Illinois, 60612, United States
Tulane Sickle Cell Ctr- So LA
Metairie, Louisiana, 70002, United States
Mass General Cancer Center
Boston, Massachusetts, 02114, United States
Wayne State University/University Health Center
Detroit, Michigan, 48201, United States
Children's Hospitals And Clinics Of Minnesota
Minneapolis, Minnesota, 55404, United States
University of Minnesota_Minneapolis_0
Minneapolis, Minnesota, 55455, United States
Mississippi Center Advanced Medicine
Madison, Mississippi, 39110, United States
Univ of NE Med Center_Omaha
Omaha, Nebraska, 68198, United States
Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Interfaith Medical Center
Brooklyn, New York, 11238, United States
Queens Hospital Center
Jamaica, New York, 11432-1121, United States
Mount Sinai School of Medicine
New York, New York, 10029, United States
Jacobi Medical Center
The Bronx, New York, 10461, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
University of North Carlolina-Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Atrium Levine Children's/Atrium Health
Charlotte, North Carolina, 28204, United States
Duke Comprehen Sickle Cell
Durham, North Carolina, 27710, United States
East Carolina Univ-Greenville
Greenville, North Carolina, 27834-4300, United States
East Carolina Univ-Greenville
Greenville, North Carolina, 27834, United States
Dayton Children's Hosptial
Dayton, Ohio, 45404, United States
Univ Oklahoma HSC_Okla City
Oklahoma City, Oklahoma, 73104, United States
University of Oklahoma Health Sciences Center_Oklahoma City
Oklahoma City, Oklahoma, 73104, United States
Penn Comprehensive Hemophilia & Thrombosis Program
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
St Christopher Hosp for Child
Philadelphia, Pennsylvania, 19134, United States
Hemophilia Center of Western PA
Pittsburgh, Pennsylvania, 15213, United States
Medical Univ of SC Charleston
Charleston, South Carolina, 29425, United States
University Of Tennessee
Memphis, Tennessee, 38163, United States
Baylor College of Medicine Texas Childen's Hospital
Houston, Texas, 77030, United States
Baylor College of Medicine_Houston
Houston, Texas, 77030, United States
Dan L. Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Univ Texas HSC-Houston
Houston, Texas, 77030, United States
University Of Virginia Hospital
Charlottesville, Virginia, 22908, United States
Medical College of Wisconsin & Zablocki VAMC
Milwaukee, Wisconsin, 53226, United States
Univ of Alberta Hosp Edmonton
Edmonton, Alberta, T6G 2B7, Canada
LHSC - Victoria Hospital
London, Ontario, N6A 5W9, Canada
LHSC - Victoria Hospital
London, Ontario, ON N6A 5W9, Canada
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Toronto General Hospital, Liver Clinic
Toronto, Ontario, M5G 2C4, Canada
Toronto General Hospital, Liver Clinic
Toronto, Ontario, M5G2C4, Canada
Hospitalier de l'Universite de Montreal (CHUM)-Hôpital Notre
Montreal, Quebec, H2L 4M1, Canada
McGill University Health Centre
Montreal, Quebec, H4A 3J1, Canada
Ap-Hp-Hopital Henri Mondor
Créteil, 94000, France
Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-3
Grenoble, 38043, France
Hospices Civils de Lyon-Hopital Edouard Herriot
Lyon, 69437, France
Ap-Hp-Hopital Europeen Georges Pompidou
Paris, 75015, France
Aghia Sophia Childrens' Hospital
Goudi, 11527, Greece
General Hospital Of Larissa Koutlibaneio And Triantafylleio - Thalassemia and SCD Unit
Larissa, 41221, Greece
Gen Univ Hospital of Patras, Thalassemia/Hemoglobinopathies
Pátrai, 26504, Greece
Gauhati Medical College and Hospital
Guwahati, Assam, 781032, India
All India Institute of Medical Sciences (AIIMS), Raipur
Raipur, Chhattisgarh, 492099, India
Zydus Medical College & Hospital
Dohad, Gujarat, 389151, India
Nirmal Hospital Pvt. Ltd.
Surat, Gujarat, 395002, India
BAPS Pramukh Swami Hospital
Surat, Gujarat, 395009, India
SSG Hospital, Baroda
Vadodara, Gujarat, 390001, India
SSG Hospital, Baroda
Vadodara, Gujarat, 390006, India
Victoria Hospital (Bangalore Medical College and Research Institute)
Bangalore, Karnataka, 560002, India
J.S.S.Hospital
Mysore, Karnataka, 570004, India
Government Medical College, Kozhikode
Kozhikode, Kerala, 673008, India
K.J Somaiya Hospital and Research Centre
Mumbai, Maharashtra, 400022, India
Government Medical College and Hospital
Nagpur, Maharashtra, 440003, India
Government Medical College and Super Speciality Hospital, Nagpur
Nagpur, Maharashtra, 440003, India
Government Medical College and Super Speciality Hospital, Nagpur
Nagpur, Maharashtra, 440009, India
IMS and SUM Hospital
Bhubaneswar, Odisha, 751003, India
S.C.B. Medical College
Cuttack, Odisha, 753007, India
Christian Medical College Hospital, Vellore
Ranipet, Tamil Nadu, 632517, India
Christian Medical College Hospital, Vellore
Vellore, Tamil Nadu, 632004, India
Yashoda hospital
Hyderabad, Telangana, 500082, India
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Lucknow, Uttar Pradesh, 226014, India
NRS Medical College & Hospital
Kolkata, West Bengal, 700014, India
NRS Medical College & Hospital
Kolkata, West Bengal, 70014, India
KIMS - Kingsway Hospital
Nagpur, 440001, India
Ospedali Galliera
Genova, 16128, Italy
Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122, Italy
Azienda Ospedale Universita Padova
Padova, 35128, Italy
Azienda Ospedaliera Universitaria Integrata Verona Policlinico GB Rossi - Borgo Roma
Verona, 37134, Italy
Policlinico GB Rossi
Verona, 37134, Italy
Abdali Hospital
Amman, Jordan
Istiklal Hospital
Amman, Jordan
The Specialty Hospital, Advanced Clinical Center
Amman, Jordan
Irbid Specialty Hospital Clinical Research Center
Irbid, Jordan
King Abdullah University Hospital
Irbid, Jordan
Hospital Nini
Tripoli, 1434, Lebanon
Sultan Qaboos University Hospital
Muscat, Sultanet of Oman/Muscat/Al Khoud, 123, Oman
Charlotte Maxeke Johannesburg Academic Hospital
Parktown, Johannesburg, Gauteng, 2193, South Africa
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Regional Universitario de Málaga
Málaga, 29010, Spain
Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie
Zurich, 8091, Switzerland
Acıbadem Adana Hastanesi-Hematoloji
Adana, 01130, Turkey (Türkiye)
Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji
Adana, 01130, Turkey (Türkiye)
Hacettepe Üniversitesi Hastanesi- Hematoloji
Ankara, 06230, Turkey (Türkiye)
Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji
Mersin, 33110, Turkey (Türkiye)
University Hospital of Wales
Cardiff, CF14 4XW, United Kingdom
Royal London Hospital_London
London, E1 1BB, United Kingdom
University College Hospital - Paediatric Services
London, NW1 2PG, United Kingdom
Central Middlesex Hospital
London, NW10 7NS, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
King's College Hospital
London, SE5 9RS, United Kingdom
Manchester Royal Infirmary
Manchester, M13 9WL, United Kingdom
Related Publications (2)
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. 2026 Jan 1;216:107353. doi: 10.1016/j.ejps.2025.107353. Epub 2025 Oct 27.
PMID: 41161613DERIVEDAbbasi 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.
PMID: 40569673DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Transparency (dept. 2834)
Novo Nordisk A/S
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 31, 2022
First Posted
June 6, 2022
Study Start
July 7, 2022
Primary Completion
July 24, 2025
Study Completion
July 24, 2025
Last Updated
July 22, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
"According to the Novo Nordisk disclosure commitment on novonordisk-trials.com"