| CTRI Number |
CTRI/2023/01/049275 [Registered on: 30/01/2023] Trial Registered Prospectively |
| Last Modified On: |
24/02/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Research study investigating how well NDec works in people with sickle cell disease |
|
Scientific Title of Study
|
A multicentre trial evaluating the efficacy and safety of oral decitabine-tetrahydrouridine (NDec) in patients with sickle cell disease |
| Trial Acronym |
ASCENT 1 (NN7533-4470) |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 2020-003485-39 |
EudraCT |
| NCT05405114 |
ClinicalTrials.gov |
| NN7533-4470 version 7.0 dated 11-Sep-2023 |
Protocol Number |
| U1111-1255-1324 |
UTN |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Maya Sharma |
| Designation |
Vice President - Clinical, Medical, Regulatory & Pharmacovigilance |
| Affiliation |
Novo Nordisk India Private Ltd |
| Address |
Novo Nordisk India Private Limited, Nxt Tower - 2 Floor 1 & 2 Embassy Manyata Business Park Nagavara Village Kasaba Hobli Bangalore – 560045 India
Novo Nordisk India Private Limited, Nxt Tower - 2 Floor 1 & 2 Embassy Manyata Business Park Nagavara Village Kasaba Hobli Bangalore – 560045 India
Bangalore
KARNATAKA
560045
India |
| Phone |
9911497869 |
| Fax |
080-41123518 |
| Email |
yrms@novonordisk.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Maya Sharma |
| Designation |
Vice President - Clinical, Medical, Regulatory & Pharmacovigilance |
| Affiliation |
Novo Nordisk India Private Ltd |
| Address |
Novo Nordisk India Private Limited, Nxt Tower - 2 Floor 1 & 2 Embassy Manyata Business Park Nagavara Village Kasaba Hobli Bangalore – 560045 India
Novo Nordisk India Private Limited, Nxt Tower - 2 Floor 1 & 2 Embassy Manyata Business Park Nagavara Village Kasaba Hobli Bangalore – 560045 India
Bangalore
KARNATAKA
560045
India |
| Phone |
9911497869 |
| Fax |
080-41123518 |
| Email |
yrms@novonordisk.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Novo Nordisk A/S, Novo Allé, 2880 Bagsvaerd Denmark |
|
Primary Sponsor
Modification(s)
|
| Name |
Novo Nordisk India Private Limited |
| Address |
Nxt Tower - 2, Floor 1 & 2,
Embassy Manyata Business Park,
Nagavara Village, Kasaba Hobli, Bangalore - 560045. India
Tel No.: 080-40303200 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
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Countries of Recruitment
Modification(s)
|
Greece
India
South Africa
Spain
Turkey
Canada
France
United Kingdom
United States of America
Italy
Lebanon |
Sites of Study
Modification(s)
|
| No of Sites = 13 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Pankaj Kumar Kannauje |
AIIMS Raipur |
Department of General Medicine, Room no 413, D Block, 4th floor, Gate no 4, AIIMS Raipur, Tatibandh, GE Road, Raipur, Chhattisgarh – 492099, India
Raipur
CHHATTISGARH |
9752696488
drpankajkannauje@aiimsraipur.edu.in |
| Dr Ashish Kantilal Singwala |
BAPS Pramukh Swami Hospital |
BAPS Pramukh Swami Hospital, Shri Pramukh Swami Maharaj Marg, Adajan Char Rasta, Adajan, Surat - 395009, Gujrat, India
Surat
GUJARAT |
9825178504
ashishsingwalabaps@gmail.com |
| Dr Uday Prakash Kulkarni |
Christian Medical College Vellore |
Christian Medical College IDA Scudder Rd Sripuram Beripettai Vellore Tamil Nadu 632004
Vellore
TAMIL NADU |
04172-224482
kulkarni.uday@cmcvellore.ac.in |
| Dr Atkar Chandrashekhar Madhukarrao |
Government Medical College Nagpur |
Government Medical College 43GW CR2 Hanuman Nagar Ajni Rd Medical Chowk Ajni Nagpur Maharashtra 440003
Nagpur
MAHARASHTRA |
7122701637
cmatkar92@gmail.com |
| Dr Abdul Majeed K |
Government Medical College, Kozhikode |
Government Medical College, Medical College Junction, Mavoor Road, Medical College PO, Kozhikode-673008, Kerala, India
Kozhikode
KERALA |
9447311247
majeedonco@gmail.com |
| Dr Priyanka Samal |
Institute of Medical Sciences (IMS) and SUM Hospital |
K8- Kalinganagar, Bhubaneswar, Odisha, 751003, India
Khordha
ORISSA |
8902621993
samalpriyanka80@gmail.com |
| Dr Shrinath Kshirsagar |
K.J Somaiya Hospital and Research Centre |
K.J Somaiya Hospital and Research Centre, Somaiya Ayurvihar, Eastern Express Highway, Sion East, Mumbai - 400022, Maharashtra, India
Pune
MAHARASHTRA |
9821556030
shrinathk2000@gmail.com |
| Dr Harshawardhan Bora |
KIMS - Kingsway Hospital |
KIMS - Kingsway Hospital, 44, Parwana Bhawan, Kingsway, Near Kasturchand Park, Nagpur - 440001, Maharashtra, India
Nagpur
MAHARASHTRA |
9822363585
harshwardhanbora@gmail.com |
| Dr Dharmesh Rameshbhai Vaghasiya |
Nirmal Hospital Pvt Ltd |
Ring Road, Surat - 395002, Gujarat
Surat
GUJARAT |
7767054520
drdharmeshrvaghasiya@gmail.com |
| Dr Tuphan Kanti Dolai |
NRS Medical College & Hospital |
NRS Medical College & Hospital, Haematology Department, 138 AJC Bose Road, Kolkata – 700014, West Bengal, India
Kolkata
WEST BENGAL |
9874890275
tkdolai@hotmail.com |
| Dr Rabindra Kumar Jena |
SCB Medical College & Hospital |
Dept. Of Clinical Haematology,
1st Floor, Old Medicine Building, SCB Medical College & Hospital,
Cuttack – 753007, Odisha, India
Cuttack
ORISSA |
9437022343
rkjena@msn.com |
| Dr Rupal Vikas Dosi |
SSG Hsopital |
Clinical Study Room, 2nd Floor, New Emergency Building, SSG Hsopital, Medical College - Baroda, Jail Road, Vadodara - 390001, Gujarat, India
Vadodara
GUJARAT |
9824083734
ssghospital.ct@spearsmind.com |
| Dr Meera V |
Victoria Hospital (Bangalore Medical College & Research Institute) |
Department of clinical Haematology, New OPD block 5 th floor, Victoria Hospital, Mysore Road near city market, near Thargupet Bangalore, Karnataka -560002
Bangalore
KARNATAKA |
9845134167
meerachakra@yahoo.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 13 |
| Name of Committee |
Approval Status |
| BAPS Pramukh Swami Hospital Institutional Ethics Committee |
Approved |
| Ethics Committee NRS Medical College And Hospital |
Approved |
| Ethics Committee of BMCRI |
Approved |
| IEC, IMS and SUM Hospital IMS and SUM Hospital |
Approved |
| INSTITUTE ETHICS COMMITTEE, AIIMS RAIPUR |
Approved |
| Institutional Ethics Committee (IEC) Government Medical College and Hospital Nagpur |
Approved |
| Institutional Ethics Committee for Human Research Medical College |
Approved |
| Institutional Ethics Committee K.J Somaiya Medical College and Research Centre |
Approved |
| Institutional Ethics Committee, Government Medical College Kozhikode |
Approved |
| Institutional Ethics Committee, SCB Medical College & Hospital |
Approved |
| Institutional Review Board (Silver, Research and Ethics Committee) |
Approved |
| Kingsway Hospitals Ethics Committee |
Approved |
| Nirmal Hospital Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
Modification(s)
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D572||Sickle-cell/Hb-C disease, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Comparator Agent |
HU - Hydroxyurea |
Participants will get capsules daily (oral administration) according to local labelling |
| Intervention |
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 |
| Comparator Agent |
Placebo |
Participants will get capsules (oral administration) to take once or twice weekly. The number of capsules will be based on their body weight |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Age above or equal to 18 years at the time of signing informed consent
2. Confirmed diagnosis of SCD (including HbSS, HbSC, HbS beta zero thalassaemia and HbS beta plus thalassaemia or other Sickle Cell disease variants)
3. 2-10 episodes of documented vaso-occlusive crisis (VOCs) within the last 12 months prior to the screening visit
4. Haemoglobin greater than or equal to 5.0 g/dL and below or equal to 10.5 g/dL at visit 1
5. Absolute reticulocyte count above upper limit of the normal (ULN) at visit 1
6. Body weight 40 to 125 kg (inclusive) |
|
| ExclusionCriteria |
| Details |
1. 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
2. Receipt of erythropoietin or other haematopoietic growth factor treatment within 28 days of signing ICF, or planned treatment with these agents during the trial
3. 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
4. Platelet count greater than 800 x 10 to the power of 9 per L at visit 1
5. Absolute neutrophil count below or equal to 1.5 x 10 to the power of 9 per L at visit 1
6. Any condition per concurrent chronic disease involving the stomach or small intestine which may affect drug absorption, as per investigators judgement
7. Female who is
a. pregnant, breast-feeding or intends to become pregnant within 6 months after the final trial product administration
b. 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
8. 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:
a. Six (6) months after the last dose of trial product for patients on NDec or Placebo
b. Six (6) months after the last dose of trial product for patients outside US and CA randomised to HU
c. Twelve (12) months after the last dose of trial product for patients randomised to HU in US and CA |
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Method of Generating Random Sequence
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Computer generated randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
| Change in total haemoglobin |
[Time Frame: From baseline (week 0) to week 24] measured in g/dL |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Cmax for decitabine from pharmacokinetic assessment |
[Time Frame: At week 24]
measured in ng/mL |
| Cmax for tetrahydrouridine from pharmacokinetic assessment |
[Time Frame: At week 24]
measured in ng/mL |
| Change in DNA methyltransferase 1 (DNMT1) activity |
[Time Frame: From baseline (week 0) to week 24]
measured in MFI units |
| Change in cytidine deaminase (CDA) activity |
[Time Frame: From baseline (week 0) to week 24]
µmol/L/min |
| Change in foetal haemoglobin (g/dL) |
[Time Frame: From baseline (week 0) to week 24]
measured in g/dL |
| Change in foetal haemoglobin as a proportion of total haemoglobin (%HbF) |
[Time Frame: From baseline (week 0) to week 24]
measured in % |
| Change in F-cell level as a proportion of total red blood cell (RBC) (%F-cells) |
[Time Frame: From baseline (week 0) to week 24]
measured in % |
| Change in haemolysis measure: absolute reticulocyte count |
[Time Frame: From baseline (week 0) to week 24]
measured in cells × 10000000000/L |
| Change in haemolysis measure: indirect bilirubin |
[Time Frame: From baseline (week 0) to week 24]
measured in mg/dL |
| Change in haemolysis measure: lactate dehydrogenase |
[Time Frame: From baseline (week 0) to week 24]
measured in U/L |
| Number of vaso-occlusive crises |
[Time Frame: From baseline (week 0) to week 48]
number of events |
| Number of acute chest syndrome |
[Time Frame: From baseline (week 0) to week 48]
number of events |
| Number of RBC units transfused |
[Time Frame: From baseline (week 0) to week 48]
measured in Units |
| Number of adverse events of grade 3 or higher |
[Time Frame: From baseline (week 0) to week 52]
number of events |
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Target Sample Size
Modification(s)
|
Total Sample Size="84"
Sample Size from India="45"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
22/03/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
07/07/2022 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
Estimated Duration of Trial
Modification(s)
|
Years="3"
Months="0"
Days="16" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
Nil |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
Modification(s)
|
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. |