Research study investigating how well NDec works in people with sickle cell disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

22 Sep 2022 → 24 Jul 2025

Decision date (initial)

2024-07-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-508506-22-00

EudraCT number

2020-003485-39

WHO UTN

U1111-1255-1324

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety, Efficacy

To investigate the efficacy of two dosing regimens of oral decitabine-tetrahydrouridine (NDec) combination as measured by improvement in haemoglobin compared to placebo in hydroxyurea (HU)-non-eligible patients with sickle cell disease (SCD)

Secondary objectives 3

1. To investigate the safety and tolerability of NDec in HU-non-eligible patients with SCD compared to placebo
2. To evaluate clinical efficacy measures of NDec in HU-non-eligible patients with SCD compared to placebo
3. To further describe the pharmacokinetics and pharmacodynamics of NDec in HU-non-eligible patients with SCD

Conditions and MedDRA coding

Sickle cell disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age above or equal to 18 years at the time of signing informed consent
2. Confirmed diagnosis of SCD (including HbSS, HbSC, HbSβ0 thalassaemia and HbSβ+ thalassaemia or other Sickle Cell disease variants)
3. 2–10 episodes of documented VOCs within the last 12 months prior to the screening visit
4. Haemoglobin ≥5.0 g/dL and ≤10.5 g/dL at visit 1
5. Absolute reticulocyte (absolute) count above ULN at visit 1
6. Body weight 40 to 125 kg (inclusive)

Exclusion criteria 11

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 >800 x 10^9/L at visit 1
5. Absolute neutrophil count ≤1.5 x 10^9/L at visit 1
6. Any condition/concurrent chronic disease involving the stomach or small intestine which may affect drug absorption, as per investigator's judgement
7. Female who is: pregnant, breast-feeding or intends to become pregnant within 6 months after the final trial product administration or
8. Female who is: 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
9. 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
10. 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 outside US and CA randomised to HU
11. 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 Twelve (12) months after the last dose of trial product for patients randomised to HU in US and CA

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline (week 0) to week 24 in total haemoglobin in g/dL

Secondary endpoints 14

1. Cmax (maximum concentration) for decitabine from pharmacokinetic assessment At week 24 in ng/mL
2. Cmax (maximum concentration) for tetrahydrouridine from pharmacokinetic assessment at week 24 in ng/mL
3. Change in DNMT1 activity From baseline (week 0) to week 24 in MFI
4. Change in CDA activity From baseline (week 0) to week 24 in µmol/L/min
5. Change in foetal haemoglobin (g/dL) From baseline (week 0) to week 24 in g/dL
6. Change in foetal haemoglobin as a proportion of total haemoglobin (%HbF) From baseline (week 0) to week 24 in %
7. Change in F-cell level as a proportion of total red blood cells (%F-cells) From baseline (week 0) to week 24 in %
8. Change in haemolysis measure: absolute reticulocyte count From baseline (week 0) to week 24 in cells × 10^9/L
9. Change in haemolysis measure: indirect bilirubin From baseline (week 0) to week 24 in mg/dL
10. Change in haemolysis measure: lactate dehydrogenase From baseline (week 0) to week 24 in U/L
11. Number of vaso-occlusive crises From baseline (week 0) to week 48 in Number of events
12. Number of acute chest syndrome From baseline (week 0) to week 48 in Number of events
13. Number of RBC units transfused From baseline (week 0) to week 48 in units
14. Number of adverse events of grade 3 or higher From baseline (week 0) to week 52 in Number of events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 10

Locations

4 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications