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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05405114




Registration number
NCT05405114
Ethics application status
Date submitted
31/05/2022
Date registered
6/06/2022

Titles & IDs
Public title
Research Study Investigating How Well NDec Works in People With Sickle Cell Disease
Scientific title
A Multicentre Trial Evaluating the Efficacy and Safety of Oral Decitabine Tetrahydrouridine (NDec) in Patients With Sickle Cell Disease
Secondary ID [1] 0 0
U1111-1255-1324
Secondary ID [2] 0 0
NN7533-4470
Universal Trial Number (UTN)
Trial acronym
ASCENT1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sickle Cell Disease 0 0
Condition category
Condition code
Blood 0 0 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NDec - oral decitabine-tetrahydrouridine
Treatment: Drugs - HU - Hydroxyurea
Treatment: Drugs - Placebo

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

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

Placebo comparator: HU-non-eligible - Placebo plus placebo - HU-non eligible patients randomised to treatment with placebo on both days

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

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

Active comparator: HU-active - HU - HU-active patients randomised to continue on open-label HU treatment


Treatment: Drugs: 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

Treatment: Drugs: HU - Hydroxyurea
Participants will get capsules daily (oral administration) according to local labelling

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in total haemoglobin
Timepoint [1] 0 0
From baseline (week 0) to week 24
Secondary outcome [1] 0 0
Cmax for decitabine from pharmacokinetic assessment
Timepoint [1] 0 0
At week 24
Secondary outcome [2] 0 0
Cmax for tetrahydrouridine from pharmacokinetic assessment
Timepoint [2] 0 0
At week 24
Secondary outcome [3] 0 0
Change in DNA methyltransferase 1 (DNMT1) activity
Timepoint [3] 0 0
From baseline (week 0) to week 24
Secondary outcome [4] 0 0
Change in cytidine deaminase (CDA) activity
Timepoint [4] 0 0
From baseline (week 0) to week 24
Secondary outcome [5] 0 0
Change in foetal haemoglobin (g/dL)
Timepoint [5] 0 0
From baseline (week 0) to week 24
Secondary outcome [6] 0 0
Change in foetal haemoglobin as a proportion of total haemoglobin (%HbF)
Timepoint [6] 0 0
From baseline (week 0) to week 24
Secondary outcome [7] 0 0
Change in F-cell level as a proportion of total red blood cell (RBC) (%F-cells)
Timepoint [7] 0 0
From baseline (week 0) to week 24
Secondary outcome [8] 0 0
Change in haemolysis measure: absolute reticulocyte count
Timepoint [8] 0 0
From baseline (week 0) to week 24
Secondary outcome [9] 0 0
Change in haemolysis measure: indirect bilirubin
Timepoint [9] 0 0
From baseline (week 0) to week 24
Secondary outcome [10] 0 0
Change in haemolysis measure: lactate dehydrogenase
Timepoint [10] 0 0
From baseline (week 0) to week 24
Secondary outcome [11] 0 0
Number of vaso-occlusive crises
Timepoint [11] 0 0
From baseline (week 0) to week 48
Secondary outcome [12] 0 0
Number of acute chest syndrome
Timepoint [12] 0 0
From baseline (week 0) to week 48
Secondary outcome [13] 0 0
Number of RBC units transfused
Timepoint [13] 0 0
From baseline (week 0) to week 48
Secondary outcome [14] 0 0
Number of adverse events of grade 3 or higher
Timepoint [14] 0 0
From baseline (week 0) to week 52

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/07/2025
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Mississippi
Country [9] 0 0
United States of America
State/province [9] 0 0
Nevada
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
France
State/province [18] 0 0
Grenoble Cedex 9
Country [19] 0 0
France
State/province [19] 0 0
Lyon Cedex 03
Country [20] 0 0
Greece
State/province [20] 0 0
Goudi
Country [21] 0 0
Greece
State/province [21] 0 0
Larissa
Country [22] 0 0
Greece
State/province [22] 0 0
Patra
Country [23] 0 0
India
State/province [23] 0 0
Chhattisgarh
Country [24] 0 0
India
State/province [24] 0 0
Gujarat
Country [25] 0 0
India
State/province [25] 0 0
Karnataka
Country [26] 0 0
India
State/province [26] 0 0
Kerala
Country [27] 0 0
India
State/province [27] 0 0
Maharashtra
Country [28] 0 0
India
State/province [28] 0 0
Orissa
Country [29] 0 0
India
State/province [29] 0 0
Tamil Nadu
Country [30] 0 0
India
State/province [30] 0 0
Telengana
Country [31] 0 0
India
State/province [31] 0 0
Uttar Pradesh
Country [32] 0 0
India
State/province [32] 0 0
West Bengal
Country [33] 0 0
India
State/province [33] 0 0
Nagpur
Country [34] 0 0
Italy
State/province [34] 0 0
Genova
Country [35] 0 0
Italy
State/province [35] 0 0
Milan
Country [36] 0 0
Italy
State/province [36] 0 0
Padova
Country [37] 0 0
Italy
State/province [37] 0 0
Verona
Country [38] 0 0
Lebanon
State/province [38] 0 0
Tripoli
Country [39] 0 0
Oman
State/province [39] 0 0
Muscat
Country [40] 0 0
South Africa
State/province [40] 0 0
Gauteng
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Málaga
Country [43] 0 0
Turkey
State/province [43] 0 0
Adana
Country [44] 0 0
Turkey
State/province [44] 0 0
Ankara
Country [45] 0 0
Turkey
State/province [45] 0 0
Mersin
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Cardiff
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Transparency (dept. 2834)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novo Nordisk
Address 0 0
Country 0 0
Phone 0 0
(+1) 866-867-7178
Fax 0 0
Email 0 0
clinicaltrials@novonordisk.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
"According to the Novo Nordisk disclosure commitment on novonordisk-trials.com"
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://novonordisk-trials.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05405114