Research Study Investigating How Well NDec Works in People With Sickle Cell Disease (ASCENT1)
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| ClinicalTrials.gov Identifier: NCT05405114 |
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Recruitment Status :
Recruiting
First Posted : June 6, 2022
Last Update Posted : March 27, 2023
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Sponsor:
Novo Nordisk A/S
Information provided by (Responsible Party):
Novo Nordisk A/S
- Study Details
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Sickle Cell Disease | Drug: NDec - oral decitabine-tetrahydrouridine Drug: HU - Hydroxyurea Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 84 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicentre Trial Evaluating the Efficacy and Safety of Oral Decitabine Tetrahydrouridine (NDec) in Patients With Sickle Cell Disease |
| Actual Study Start Date : | July 7, 2022 |
| Estimated Primary Completion Date : | November 15, 2023 |
| Estimated Study Completion Date : | June 21, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Sickle cell disease
Drug Information available for:
Decitabine
| Arm | Intervention/treatment |
|---|---|
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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
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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 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 |
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Experimental: HU-non-eligible - NDec plus NDec
HU-non eligible patients randomised to treatment with NDec on both days
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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 |
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Placebo Comparator: HU-non-eligible - Placebo plus placebo
HU-non eligible patients randomised to treatment with placebo on both days
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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 |
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Experimental: HU-active - NDec plus placebo
HU-active patients randomised to treatment with NDec on one day and placebo on the other day
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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 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 |
|
Experimental: HU-active - NDec plus NDec
HU-active patients randomised to treatment with NDec on both days
|
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 |
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Active Comparator: HU-active - HU
HU-active patients randomised to continue on open-label HU treatment
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Drug: HU - Hydroxyurea
Participants will get capsules daily (oral administration) according to local labelling |
Primary Outcome Measures :
- Change in total haemoglobin [ Time Frame: From baseline (week 0) to week 24 ]measured in g/dL
Secondary Outcome Measures :
- 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 × 10^9/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
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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)
- 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
- 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
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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
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05405114
Contacts
| Contact: Novo Nordisk | (+1) 866-867-7178 | clinicaltrials@novonordisk.com |
Locations
| United States, California | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Oakland, California, United States, 94609 | |
| Novo Nordisk Investigational Site | Recruiting |
| Orange, California, United States, 92868 | |
| Novo Nordisk Investigational Site | Recruiting |
| Torrance, California, United States, 90502-2004 | |
| United States, Colorado | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Aurora, Colorado, United States, 80045 | |
| United States, District of Columbia | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Washington, District of Columbia, United States, 20060 | |
| United States, Florida | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Hollywood, Florida, United States, 33023 | |
| United States, Illinois | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Chicago, Illinois, United States, 60612 | |
| United States, Louisiana | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Metairie, Louisiana, United States, 70002 | |
| United States, Mississippi | |
| Novo Nordisk Investigational Site | Recruiting |
| Madison, Mississippi, United States, 39110 | |
| United States, New York | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| New York, New York, United States, 10029 | |
| United States, North Carolina | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Greenville, North Carolina, United States, 27834-4300 | |
| United States, Oklahoma | |
| Novo Nordisk Investigational Site | Recruiting |
| Oklahoma City, Oklahoma, United States, 73104 | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Oklahoma City, Oklahoma, United States, 73104 | |
| United States, Pennsylvania | |
| Novo Nordisk Investigational Site | Recruiting |
| Philadelphia, Pennsylvania, United States, 19134 | |
| United States, South Carolina | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Charleston, South Carolina, United States, 29425 | |
| United States, Texas | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Houston, Texas, United States, 77030 | |
| Canada, Ontario | |
| Novo Nordisk Investigational Site | Recruiting |
| London, Ontario, Canada, ON N6A 5W9 | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Toronto, Ontario, Canada, M5G2C4 | |
| Canada, Quebec | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Montreal, Quebec, Canada, H4A 3J1 | |
| France | |
| Novo Nordisk Investigational Site | Recruiting |
| La Tronche, France, 38700 | |
| Novo Nordisk Investigational Site | Recruiting |
| Lyon cedex 03, France, 69437 | |
| Greece | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Goudi, Greece, 11527 | |
| Novo Nordisk Investigational Site | Recruiting |
| Patra, Greece, GR-26504 | |
| India | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Surat, Gujarat, India, 395002 | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Bangalore, Karnataka, India, 560002 | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Nagpur, Maharashtra, India, 440003 | |
| Novo Nordisk Investigational Site | Recruiting |
| Bhubaneswar, Orissa, India, 751003 | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Ranipet, Tamil Nadu, India, 632517 | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Lucknow, Uttar Pradesh, India, 226014 | |
| Italy | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Genova, Italy, 16128 | |
| Novo Nordisk Investigational Site | Recruiting |
| Padova, Italy, 35128 | |
| Novo Nordisk Investigational Site | Recruiting |
| Verona, Italy, 37134 | |
| South Africa | |
| Novo Nordisk Investigational Site | Recruiting |
| Parktown, Johannesburg, Gauteng, South Africa, 2193 | |
| Spain | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Madrid, Spain, 28046 | |
| Novo Nordisk Investigational Site | Recruiting |
| Málaga, Spain, 29010 | |
| Turkey | |
| Novo Nordisk Investigational Site | Recruiting |
| Adana, Turkey, 01130 | |
| Novo Nordisk Investigational Site | Recruiting |
| Mersin, Turkey, 33110 | |
| United Kingdom | |
| Novo Nordisk Investigational Site | Recruiting |
| Cardiff, United Kingdom, CF14 4XW | |
| Novo Nordisk Investigational Site | Recruiting |
| London, United Kingdom, NW10 7NS | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| London, United Kingdom, SE1 9RT | |
| Novo Nordisk Investigational Site | Recruiting |
| London, United Kingdom, SE5 9RS | |
| Novo Nordisk Investigational Site | Not yet recruiting |
| Manchester, United Kingdom, M13 9WL | |
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
| Study Director: | Clinical Transparency (dept. 2834) | Novo Nordisk A/S |
| Responsible Party: | Novo Nordisk A/S |
| ClinicalTrials.gov Identifier: | NCT05405114 |
| Other Study ID Numbers: |
NN7533-4470 U1111-1255-1324 ( Other Identifier: World Health Organization (WHO) ) 2020-003485-39 ( EudraCT Number ) |
| First Posted: | June 6, 2022 Key Record Dates |
| Last Update Posted: | March 27, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | "According to the Novo Nordisk disclosure commitment on novonordisk-trials.com" |
| URL: | http://novonordisk-trials.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Anemia, Sickle Cell Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn Decitabine Hydroxyurea |
Tetrahydrouridine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors Antisickling Agents Nucleic Acid Synthesis Inhibitors |