Clinical trial NCT05405114: Research Study Investigating How Well NDec Works in People With Sickle Cell Disease
Official title: A Multicentre Trial Evaluating the Efficacy and Safety of Oral Decitabine Tetrahydrouridine (NDec) in Patients With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2022-06-06
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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 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

Primary outcomes:
measure: Change in total haemoglobin
timeFrame: From baseline (week 0) to week 24
Secondary outcomes:
measure: Cmax for decitabine from pharmacokinetic assessment
timeFrame: At week 24
measure: Cmax for tetrahydrouridine from pharmacokinetic assessment
timeFrame: At week 24
measure: Change in DNA methyltransferase 1 (DNMT1) activity
timeFrame: From baseline (week 0) to week 24
measure: Change in cytidine deaminase (CDA) activity
timeFrame: From baseline (week 0) to week 24
measure: Change in foetal haemoglobin (g/dL)
timeFrame: From baseline (week 0) to week 24
measure: Change in foetal haemoglobin as a proportion of total haemoglobin (%HbF)
timeFrame: From baseline (week 0) to week 24
measure: Change in F-cell level as a proportion of total red blood cell (RBC) (%F-cells)
timeFrame: From baseline (week 0) to week 24
measure: Change in haemolysis measure: absolute reticulocyte count
timeFrame: From baseline (week 0) to week 24
measure: Change in haemolysis measure: indirect bilirubin
timeFrame: From baseline (week 0) to week 24
measure: Change in haemolysis measure: lactate dehydrogenase
timeFrame: From baseline (week 0) to week 24
measure: Number of vaso-occlusive crises
timeFrame: From baseline (week 0) to week 48
measure: Number of acute chest syndrome
timeFrame: From baseline (week 0) to week 48
measure: Number of RBC units transfused
timeFrame: From baseline (week 0) to week 48
measure: Number of adverse events of grade 3 or higher
timeFrame: From baseline (week 0) to week 52
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Oakland Benioff Children's Hospital
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: Clinical and Transl Res Center
state: Colorado
city: Chicago
country: United States
facility: University Of Illinois at Chicago
state: Illinois
city: Madison
country: United States
facility: Mississippi Center Advanced Medicine
state: Mississippi
city: Las Vegas
country: United States
facility: Cure 4 the Kids Foundation
state: Nevada
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center_Oklahoma City
state: Oklahoma
city: Philadelphia
country: United States
facility: St Christopher Hosp for Child
state: Pennsylvania
city: Houston
country: United States
facility: Univ Texas HSC-Houston
state: Texas
city: London
country: Canada
facility: LHSC - Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital, Liver Clinic
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital, Liver Clinic
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Grenoble Cedex 9
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-3
city: Lyon Cedex 03
country: France
facility: Hospices Civils de Lyon-Hopital Edouard Herriot
city: Goudi
country: Greece
facility: Aghia Sophia Childrens' Hospital
city: Larissa
country: Greece
facility: General Hospital Of Larissa Koutlibaneio And Triantafylleio
city: Patra
country: Greece
facility: Gen Univ Hospital of Patras, Thalassemia/Hemoglobinopathies
city: Surat
country: India
facility: Nirmal Hospital Pvt. Ltd.
state: Gujarat
city: Surat
country: India
facility: BAPS Pramukh Swami Hospital
state: Gujarat
city: Vadodara
country: India
facility: SSG Hospital, Baroda
state: Gujarat
city: Vadodara
country: India
facility: SSG Hospital, Baroda
state: Gujarat
city: Bangalore
country: India
facility: Victoria Hospital (Bangalore Medical College and Research Institute)
state: Karnataka
city: Kozhikode
country: India
facility: Government Medical College, Kozhikode
state: Kerala
city: Nagpur
country: India
facility: Government Medical College and Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Government Medical College and Super Speciality Hospital, Nagpur
state: Maharashtra
city: Bhubaneswar
country: India
facility: IMS and SUM Hospital
state: Orissa
city: Cuttack
country: India
facility: S.C.B. Medical College
state: Orissa
city: Ranipet
country: India
facility: Christian Medical College Hospital, Vellore
state: Tamil Nadu
city: Kolkata
country: India
facility: NRS Medical College & Hospital
state: West Bengal
city: Kolkatta
country: India
facility: NRS Medical College & Hospital
state: West Bengal
city: Nagpur
country: India
facility: KIMS - Kingsway Hospital
city: Genova
country: Italy
facility: Ospedali Galliera
city: Milan
country: Italy
facility: Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
city: Padova
country: Italy
facility: Azienda Ospedale Universita Padova
city: Verona
country: Italy
facility: Policlinico GB Rossi
city: Tripoli
country: Lebanon
facility: Hospital Nini
city: Muscat
country: Oman
facility: Sultan Qaboos University Hospital
city: Parktown, Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi
city: Adana
country: Turkey
facility: Cukurova Universitesi
city: Ankara
country: Turkey
facility: Hacettepe University Hematology
city: Mersin
country: Turkey
facility: Mersin University Medical Faculty Hospital, Hematology
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: Central Middlesex Hospital
city: London
country: United Kingdom
facility: Guy's Hosptial
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: