Research Study Investigating How Well NDec Works in People With Sickle Cell Disease
- Conditions
- Sickle Cell Disease
- Interventions
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 84
- 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).
-
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 (83)
Jacobi Medical Center
🇺🇸Bronx, New York, United States
East Carolina University_Greenville_0
🇺🇸Greenville, North Carolina, United States
Univ Oklahoma HSC_Okla City
🇺🇸Oklahoma City, Oklahoma, United States
Medical Univ of SC Charleston
🇺🇸Charleston, South Carolina, United States
All India Institute of Medical Sciences (AIIMS), Raipur
🇮🇳Raipur, Chhattisgarh, India
Yashoda hospital
🇮🇳Hyderabad, Telengana, India
Azienda Ospedale Universita Padova
🇮🇹Padova, Italy
Policlinico GB Rossi
🇮🇹Verona, Italy
Hospital Nini
🇱🇧Tripoli, Lebanon
Sultan Qaboos University Hospital
🇴🇲Muscat, Oman
Charlotte Maxeke Johannesburg Academic Hospital
🇿🇦Parktown, Johannesburg, Gauteng, South Africa
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Regional de Málaga
🇪🇸Málaga, Spain
Acibadem Adana Hastanesi
🇹🇷Adana, Turkey
Cukurova Universitesi
🇹🇷Adana, Turkey
Hacettepe University Hematology
🇹🇷Ankara, Turkey
Mersin University Medical Faculty Hospital, Hematology
🇹🇷Mersin, Turkey
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Central Middlesex Hospital
🇬🇧London, United Kingdom
Guy's Hosptial
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Manchester Royal Infirmary_Manchester_0
🇬🇧Manchester, United Kingdom
University Of South Alabama
🇺🇸Mobile, Alabama, United States
Center for Inherited Blood Dis
🇺🇸Orange, California, United States
Howard University
🇺🇸Washington, District of Columbia, United States
Foundation for Sickle Cell Disease Research
🇺🇸Hollywood, Florida, United States
University of Miami Hospital & Clinics
🇺🇸Miami, Florida, United States
Tulane Sickle Cell Ctr- So LA
🇺🇸Metairie, Louisiana, United States
J.S.S.Hospital
🇮🇳Mysore, Karnataka, India
K.J Somaiya Hospital and Research Centre
🇮🇳Mumbai, Maharashtra, India
S.C.B. Medical College
🇮🇳Cuttack, Orissa, India
Christian Medical College Hospital, Vellore
🇮🇳Vellore, Tamil Nadu, India
Sanjay Gandhi Postgraduate Institute of Medical Sciences
🇮🇳Lucknow, Uttar Pradesh, India
NRS Medical College & Hospital
🇮🇳Kolkatta, West Bengal, India
KIMS - Kingsway Hospital
🇮🇳Nagpur, India
Ospedali Galliera
🇮🇹Genova, Italy
Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
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
LHSC - Victoria Hospital
🇨🇦London, Ontario, Canada
Toronto General Hospital, Liver Clinic
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-3
🇫🇷Grenoble Cedex 9, France
Hospices Civils de Lyon-Hopital Edouard Herriot
🇫🇷Lyon Cedex 03, France
Aghia Sophia Childrens' Hospital
🇬🇷Goudi, Greece
General Hospital Of Larissa Koutlibaneio And Triantafylleio
🇬🇷Larissa, Greece
Gen Univ Hospital of Patras, Thalassemia/Hemoglobinopathies
🇬🇷Patra, Greece
Nirmal Hospital Pvt. Ltd.
🇮🇳Surat, Gujarat, India
BAPS Pramukh Swami Hospital
🇮🇳Surat, Gujarat, India
SSG Hospital, Baroda
🇮🇳Vadodara, Gujarat, India
Victoria Hospital (Bangalore Medical College and Research Institute)
🇮🇳Bangalore, Karnataka, India
Government Medical College, Kozhikode
🇮🇳Kozhikode, Kerala, India
Government Medical College and Hospital
🇮🇳Nagpur, Maharashtra, India
Government Medical College and Super Speciality Hospital, Nagpur
🇮🇳Nagpur, Maharashtra, India
IMS and SUM Hospital
🇮🇳Bhubaneswar, Orissa, India
S.C.B. Medical College
🇮🇳Cuttack, Orissa, India
Christian Medical College Hospital, Vellore
🇮🇳Ranipet, Tamil Nadu, India
NRS Medical College & Hospital
🇮🇳Kolkatta, West Bengal, India
KIMS - Kingsway Hospital
🇮🇳Nagpur, India
Ospedali Galliera
🇮🇹Genova, Italy
Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
Azienda Ospedale Universita Padova
🇮🇹Padova, Italy
Policlinico GB Rossi
🇮🇹Verona, Italy
Hospital Nini
🇱🇧Tripoli, Lebanon
Sultan Qaboos University Hospital
🇴🇲Muscat, Oman
Charlotte Maxeke Johannesburg Academic Hospital
🇿🇦Parktown, Johannesburg, Gauteng, South Africa
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Acibadem Adana Hastanesi
🇹🇷Adana, Turkey
Cukurova Universitesi
🇹🇷Adana, Turkey
Hacettepe University Hematology
🇹🇷Ankara, Turkey
Mersin University Medical Faculty Hospital, Hematology
🇹🇷Mersin, Turkey
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Central Middlesex Hospital
🇬🇧London, United Kingdom
Guy's Hosptial
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom