Research Study Investigating How Well NDec Works in People With Sickle Cell Disease (ASCENT1)

Novo Nordisk

Status and phase: Enrolling; Phase 2

Conditions: Sickle Cell Disease

Treatments: Drug: HU - Hydroxyurea; Drug: Placebo; Drug: NDec - oral decitabine-tetrahydrouridine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05405114

U1111-1255-1324 (Other Identifier)

NN7533-4470

2020-003485-39 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 84 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

84 participants in 6 patient groups, including a placebo group

HU-non-eligible - NDec plus placebo

Experimental group

Description:

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

Treatment:

Drug: NDec - oral decitabine-tetrahydrouridine

Drug: Placebo

HU-non-eligible - NDec plus NDec

Experimental group

Description:

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

Treatment:

Drug: NDec - oral decitabine-tetrahydrouridine

HU-non-eligible - Placebo plus placebo

Placebo Comparator group

Description:

HU-non eligible patients randomised to treatment with placebo on both days

Treatment:

Drug: Placebo

HU-active - NDec plus placebo

Experimental group

Description:

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

Treatment:

Drug: NDec - oral decitabine-tetrahydrouridine

Drug: Placebo

HU-active - NDec plus NDec

Experimental group

Description:

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

Treatment:

Drug: NDec - oral decitabine-tetrahydrouridine

HU-active - HU

Active Comparator group

Description:

HU-active patients randomised to continue on open-label HU treatment

Treatment:

Drug: HU - Hydroxyurea