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

NCT ID: NCT05405114

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-07

Study Completion Date

2025-07-24

Brief Summary

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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

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Conditions

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Sickle Cell Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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HU-non-eligible - NDec plus placebo

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

Group Type EXPERIMENTAL

NDec - oral decitabine-tetrahydrouridine

Intervention Type DRUG

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

Placebo

Intervention Type 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-non-eligible - NDec plus NDec

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

Group Type EXPERIMENTAL

NDec - oral decitabine-tetrahydrouridine

Intervention Type 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-non-eligible - Placebo plus placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

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

Group Type EXPERIMENTAL

NDec - oral decitabine-tetrahydrouridine

Intervention Type DRUG

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

Placebo

Intervention Type 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 patients randomised to treatment with NDec on both days

Group Type EXPERIMENTAL

NDec - oral decitabine-tetrahydrouridine

Intervention Type 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 - HU

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

Group Type ACTIVE_COMPARATOR

HU - Hydroxyurea

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

HU - Hydroxyurea

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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novo Nordisk A/S

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Transparency (dept. 2834)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

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University Of South Alabama

Mobile, Alabama, United States

Site Status

UCSF Oakland Benioff Children's Hospital

Oakland, California, United States

Site Status

Center for Inherited Blood Dis

Orange, California, United States

Site Status

Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

Clinical and Transl Res Center

Aurora, Colorado, United States

Site Status

Howard University

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

Site Status

Foundation for Sickle Cell Disease Research

Hollywood, Florida, United States

Site Status

University of Miami Hospital & Clinics

Miami, Florida, United States

Site Status

University Of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Tulane Sickle Cell Ctr- So LA

Metairie, Louisiana, United States

Site Status

Mississippi Center Advanced Medicine

Madison, Mississippi, United States

Site Status

Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Jacobi Medical Center

The Bronx, New York, United States

Site Status

East Carolina Univ-Greenville

Greenville, North Carolina, United States

Site Status

Univ Oklahoma HSC_Okla City

Oklahoma City, Oklahoma, United States

Site Status

University of Oklahoma Health Sciences Center_Oklahoma City

Oklahoma City, Oklahoma, United States

Site Status

St Christopher Hosp for Child

Philadelphia, Pennsylvania, United States

Site Status

Medical Univ of SC Charleston

Charleston, South Carolina, United States

Site Status

Univ Texas HSC-Houston

Houston, Texas, United States

Site Status

LHSC - Victoria Hospital

London, Ontario, Canada

Site Status

Toronto General Hospital, Liver Clinic

Toronto, Ontario, Canada

Site Status

Toronto General Hospital, Liver Clinic

Toronto, Ontario, Canada

Site Status

McGill University Health Centre

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-3

Grenoble, , France

Site Status

Hospices Civils de Lyon-Hopital Edouard Herriot

Lyon, , France

Site Status

Aghia Sophia Childrens' Hospital

Goudi, , Greece

Site Status

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

Larissa, , Greece

Site Status

Gen Univ Hospital of Patras, Thalassemia/Hemoglobinopathies

Pátrai, , Greece

Site Status

All India Institute of Medical Sciences (AIIMS), Raipur

Raipur, Chhattisgarh, India

Site Status

Nirmal Hospital Pvt. Ltd.

Surat, Gujarat, India

Site Status

BAPS Pramukh Swami Hospital

Surat, Gujarat, India

Site Status

SSG Hospital, Baroda

Vadodara, Gujarat, India

Site Status

SSG Hospital, Baroda

Vadodara, Gujarat, India

Site Status

Victoria Hospital (Bangalore Medical College and Research Institute)

Bangalore, Karnataka, India

Site Status

J.S.S.Hospital

Mysore, Karnataka, India

Site Status

Government Medical College, Kozhikode

Kozhikode, Kerala, India

Site Status

K.J Somaiya Hospital and Research Centre

Mumbai, Maharashtra, India

Site Status

Government Medical College and Hospital

Nagpur, Maharashtra, India

Site Status

Government Medical College and Super Speciality Hospital, Nagpur

Nagpur, Maharashtra, India

Site Status

Government Medical College and Super Speciality Hospital, Nagpur

Nagpur, Maharashtra, India

Site Status

IMS and SUM Hospital

Bhubaneswar, Odisha, India

Site Status

S.C.B. Medical College

Cuttack, Odisha, India

Site Status

Christian Medical College Hospital, Vellore

Ranipet, Tamil Nadu, India

Site Status

Christian Medical College Hospital, Vellore

Vellore, Tamil Nadu, India

Site Status

Yashoda hospital

Hyderabad, Telangana, India

Site Status

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Lucknow, Uttar Pradesh, India

Site Status

NRS Medical College & Hospital

Kolkata, West Bengal, India

Site Status

NRS Medical College & Hospital

Kolkata, West Bengal, India

Site Status

KIMS - Kingsway Hospital

Nagpur, , India

Site Status

Ospedali Galliera

Genova, , Italy

Site Status

Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Azienda Ospedale Universita Padova

Padua, , Italy

Site Status

Azienda Ospedaliera Universitaria Integrata Verona Policlinico GB Rossi - Borgo Roma

Verona, , Italy

Site Status

Policlinico GB Rossi

Verona, , Italy

Site Status

Hospital Nini

Tripoli, , Lebanon

Site Status

Sultan Qaboos University Hospital

Muscat, , Oman

Site Status

Charlotte Maxeke Johannesburg Academic Hospital

Parktown, Johannesburg, Gauteng, South Africa

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Regional Universitario de Málaga

Málaga, , Spain

Site Status

Acıbadem Adana Hastanesi-Hematoloji

Adana, , Turkey (Türkiye)

Site Status

Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji

Adana, , Turkey (Türkiye)

Site Status

Hacettepe Üniversitesi Hastanesi- Hematoloji

Ankara, , Turkey (Türkiye)

Site Status

Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji

Mersin, , Turkey (Türkiye)

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

Central Middlesex Hospital

London, , United Kingdom

Site Status

Guy's Hosptial

London, , United Kingdom

Site Status

Kings College Hospital

London, , United Kingdom

Site Status

Manchester Royal Infirmary

Manchester, , United Kingdom

Site Status

Countries

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Switzerland United States Canada France Greece India Italy Lebanon Oman South Africa Spain Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 41161613 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40569673 (View on PubMed)

Other Identifiers

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U1111-1255-1324

Identifier Type: OTHER

Identifier Source: secondary_id

2020-003485-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NN7533-4470

Identifier Type: -

Identifier Source: org_study_id