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

Sickle Cell Disease Clinical Trial

— ASCENT1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05405114
• Other study ID #: NN7533-4470
• Secondary ID: U1111-1255-13242
• Status: Recruiting
• Phase: Phase 2
• Start date: July 7, 2022
• Est. completion date: May 29, 2025

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: May 29, 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age above or equal to 18 years at the time of signing informed consent

• Confirmed diagnosis of SCD (including HbSS, HbSC, HbSß0 thalassaemia and HbSß+ 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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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
• HU - Hydroxyurea
Participants will get capsules daily (oral administration) according to local labelling
• Placebo
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight

Locations

Country	Name	City	State
Canada	LHSC - Victoria Hospital	London	Ontario
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Toronto General Hospital, Liver Clinic	Toronto	Ontario
Canada	Toronto General Hospital, Liver Clinic	Toronto	Ontario
France	Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-3	Grenoble Cedex 9
France	Hospices Civils de Lyon-Hopital Edouard Herriot	Lyon Cedex 03
Greece	Aghia Sophia Childrens' Hospital	Goudi
Greece	General Hospital Of Larissa Koutlibaneio And Triantafylleio	Larissa
Greece	Gen Univ Hospital of Patras, Thalassemia/Hemoglobinopathies	Patra
India	Victoria Hospital (Bangalore Medical College and Research Institute)	Bangalore	Karnataka
India	Victoria Hospital (Bangalore Medical College and Research Institute)	Bangalore	Karnataka
India	IMS and SUM Hospital	Bhubaneswar	Orissa
India	S.C.B. Medical College	Cuttack	Orissa
India	Yashoda hospital	Hyderabad	Telengana
India	NRS Medical College & Hospital	Kolkatta	West Bengal
India	Government Medical College, Kozhikode	Kozhikode	Kerala
India	Sanjay Gandhi Postgraduate Institute of Medical Sciences	Lucknow	Uttar Pradesh
India	K.J Somaiya Hospital and Research Centre	Mumbai	Maharashtra
India	J.S.S.Hospital	Mysore	Karnataka
India	Government Medical College and Hospital	Nagpur	Maharashtra
India	Government Medical College and Super Speciality Hospital, Nagpur	Nagpur	Maharashtra
India	KIMS - Kingsway Hospital	Nagpur
India	KIMS - Kingsway Hospital	Nagpur
India	All India Institute of Medical Sciences (AIIMS), Raipur	Raipur	Chhattisgarh
India	Christian Medical College Hospital, Vellore	Ranipet	Tamil Nadu
India	BAPS Pramukh Swami Hospital	Surat	Gujarat
India	Nirmal Hospital Pvt. Ltd.	Surat	Gujarat
India	SSG Hospital, Baroda	Vadodara	Gujarat
India	Christian Medical College Hospital, Vellore	Vellore	Tamil Nadu
Italy	Ospedali Galliera	Genova
Italy	Ospedali Galliera	Genova
Italy	Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico	Milan
Italy	Azienda Ospedale Universita Padova	Padova
Italy	Policlinico GB Rossi	Verona
Lebanon	Hospital Nini	Tripoli
Oman	Sultan Qaboos University Hospital	Muscat
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Parktown, Johannesburg	Gauteng
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Regional de Málaga	Málaga
Turkey	Acibadem Adana Hastanesi	Adana
Turkey	Cukurova Universitesi	Adana
Turkey	Hacettepe University Hematology	Ankara
Turkey	Mersin University Medical Faculty Hospital, Hematology	Mersin
United Kingdom	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 States	Clinical and Transl Res Center	Aurora	Colorado
United States	Jacobi Medical Center	Bronx	New York
United States	Medical Univ of SC Charleston	Charleston	South Carolina
United States	University Of Illinois at Chicago	Chicago	Illinois
United States	East Carolina University_Greenville_0	Greenville	North Carolina
United States	Foundation for Sickle Cell Disease Research	Hollywood	Florida
United States	Univ Texas HSC-Houston	Houston	Texas
United States	Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Mississippi Center Advanced Medicine	Madison	Mississippi
United States	Tulane Sickle Cell Ctr- So LA	Metairie	Louisiana
United States	University of Miami Hospital & Clinics	Miami	Florida
United States	University Of South Alabama	Mobile	Alabama
United States	Mount Sinai School of Medicine	New York	New York
United States	UCSF Oakland Benioff Children's Hospital	Oakland	California
United States	Univ Oklahoma HSC_Okla City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center_Oklahoma City	Oklahoma City	Oklahoma
United States	Center for Inherited Blood Dis	Orange	California
United States	St Christopher Hosp for Child	Philadelphia	Pennsylvania
United States	Harbor-UCLA Medical Center	Torrance	California
United States	Howard University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  France,  Greece,  India,  Italy,  Lebanon,  Oman,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

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