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

NCT05405114 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: NN7533-4470U1111-1255-13242020-003485-39
• Study Type: interventional
• Target: 96
• Locations: 12 countries
• Sites: 69

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.

Conditions

Sickle Cell Disease

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

Study Arms (6)

HU-non-eligible - NDec plus placebo

EXPERIMENTAL

HU-non eligible patients randomised to treatment with NDec on one day and placebo on the other day

Drug: NDec - oral decitabine-tetrahydrouridine; Drug: Placebo

HU-non-eligible - NDec plus NDec

EXPERIMENTAL

HU-non eligible patients randomised to treatment with NDec on both days

Drug: NDec - oral decitabine-tetrahydrouridine

HU-non-eligible - Placebo plus placebo

PLACEBO COMPARATOR

HU-non eligible patients randomised to treatment with placebo on both days

Drug: Placebo

HU-active - NDec plus placebo

EXPERIMENTAL

HU-active patients randomised to treatment with NDec on one day and placebo on the other day

Drug: NDec - oral decitabine-tetrahydrouridine; Drug: Placebo

HU-active - NDec plus NDec

EXPERIMENTAL

HU-active patients randomised to treatment with NDec on both days

Drug: NDec - oral decitabine-tetrahydrouridine

HU-active - HU

ACTIVE COMPARATOR

HU-active patients randomised to continue on open-label HU treatment

Drug: HU - Hydroxyurea

Interventions

HU - Hydroxyurea DRUG

Participants will get capsules daily (oral administration) according to local labelling

HU-active - HU

NDec - oral decitabine-tetrahydrouridine DRUG

Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight

HU-active - NDec plus NDec; HU-active - NDec plus placebo; HU-non-eligible - NDec plus NDec; HU-non-eligible - NDec plus placebo

Placebo DRUG

Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight

HU-active - NDec plus placebo; HU-non-eligible - NDec plus placebo; HU-non-eligible - Placebo plus placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (69)

University Of South Alabama

Mobile, Alabama, 36617, United States

Location

UCSF Oakland Benioff Children's Hospital

Oakland, California, 94609, United States

Location

Center for Inherited Blood Dis

Orange, California, 92868, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502-2004, United States

Location

Clinical and Transl Res Center

Aurora, Colorado, 80045, United States

Location

Howard University

Washington D.C., District of Columbia, 20060, United States

Location

Foundation for Sickle Cell Disease Research

Hollywood, Florida, 33023, United States

Location

University of Miami Hospital & Clinics

Miami, Florida, 33136, United States

Location

University Of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Tulane Sickle Cell Ctr- So LA

Metairie, Louisiana, 70002, United States

Location

Mississippi Center Advanced Medicine

Madison, Mississippi, 39110, United States

Location

Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

East Carolina Univ-Greenville

Greenville, North Carolina, 27834, United States

Location

Univ Oklahoma HSC_Okla City

Oklahoma City, Oklahoma, 73104, United States

Location

University of Oklahoma Health Sciences Center_Oklahoma City

Oklahoma City, Oklahoma, 73104, United States

Location

St Christopher Hosp for Child

Philadelphia, Pennsylvania, 19134, United States

Location

Medical Univ of SC Charleston

Charleston, South Carolina, 29425, United States

Location

Univ Texas HSC-Houston

Houston, Texas, 77030, United States

Location

LHSC - Victoria Hospital

London, Ontario, ON N6A 5W9, Canada

Location

Toronto General Hospital, Liver Clinic

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto General Hospital, Liver Clinic

Toronto, Ontario, M5G2C4, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-3

Grenoble, 38043, France

Location

Hospices Civils de Lyon-Hopital Edouard Herriot

Lyon, 69437, France

Location

Aghia Sophia Childrens' Hospital

Goudi, 11527, Greece

Location

General Hospital Of Larissa Koutlibaneio And Triantafylleio - Thalassemia and SCD Unit

Larissa, 41221, Greece

Location

Gen Univ Hospital of Patras, Thalassemia/Hemoglobinopathies

Pátrai, 26504, Greece

Location

All India Institute of Medical Sciences (AIIMS), Raipur

Raipur, Chhattisgarh, 492099, India

Location

Nirmal Hospital Pvt. Ltd.

Surat, Gujarat, 395002, India

Location

BAPS Pramukh Swami Hospital

Surat, Gujarat, 395009, India

Location

SSG Hospital, Baroda

Vadodara, Gujarat, 390001, India

Location

SSG Hospital, Baroda

Vadodara, Gujarat, 390006, India

Location

Victoria Hospital (Bangalore Medical College and Research Institute)

Bangalore, Karnataka, 560002, India

Location

J.S.S.Hospital

Mysore, Karnataka, 570004, India

Location

Government Medical College, Kozhikode

Kozhikode, Kerala, 673008, India

Location

K.J Somaiya Hospital and Research Centre

Mumbai, Maharashtra, 400022, India

Location

Government Medical College and Hospital

Nagpur, Maharashtra, 440003, India

Location

Government Medical College and Super Speciality Hospital, Nagpur

Nagpur, Maharashtra, 440003, India

Location

Government Medical College and Super Speciality Hospital, Nagpur

Nagpur, Maharashtra, 440009, India

Location

IMS and SUM Hospital

Bhubaneswar, Odisha, 751003, India

Location

S.C.B. Medical College

Cuttack, Odisha, 753007, India

Location

Christian Medical College Hospital, Vellore

Ranipet, Tamil Nadu, 632517, India

Location

Christian Medical College Hospital, Vellore

Vellore, Tamil Nadu, 632004, India

Location

Yashoda hospital

Hyderabad, Telangana, 500082, India

Location

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Lucknow, Uttar Pradesh, 226014, India

Location

NRS Medical College & Hospital

Kolkata, West Bengal, 700014, India

Location

NRS Medical College & Hospital

Kolkata, West Bengal, 70014, India

Location

KIMS - Kingsway Hospital

Nagpur, 440001, India

Location

Ospedali Galliera

Genova, 16128, Italy

Location

Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Azienda Ospedale Universita Padova

Padua, 35128, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona Policlinico GB Rossi - Borgo Roma

Verona, 37134, Italy

Location

Policlinico GB Rossi

Verona, 37134, Italy

Location

Hospital Nini

Tripoli, 1434, Lebanon

Location

Sultan Qaboos University Hospital

Muscat, 123, Oman

Location

Charlotte Maxeke Johannesburg Academic Hospital

Parktown, Johannesburg, Gauteng, 2193, South Africa

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Acıbadem Adana Hastanesi-Hematoloji

Adana, 01130, Turkey (Türkiye)

Location

Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji

Adana, 01130, Turkey (Türkiye)

Location

Hacettepe Üniversitesi Hastanesi- Hematoloji

Ankara, 06230, Turkey (Türkiye)

Location

Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji

Mersin, 33110, Turkey (Türkiye)

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Central Middlesex Hospital

London, NW10 7NS, United Kingdom

Location

Guy's Hosptial

London, SE1 9RT, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

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: 41161613 DERIVED

• 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.

  PMID: 40569673 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

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: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

GB (5); OM (1); IN (21); ZA (1); TU (4); CA (4); GR (3); IT (5); US (20); LE (1); ES (2); FR (2)