Sickle Cell Disease
Conditions
Keywords
Hydroxycarbamide, Pharmacokinetic
Brief summary
The purpose of this interventional, phase II, national, multicentric, non-randomised, open-label study is to evaluate the pharmacokinetics (PK), efficacy and safety of Hydroxycarbamide Paediatric dispersible tablets with a twice daily dosing regimen in children with Sickle Celle Disease between 9 months to 11 years of age. Participants will: * Take Hydroxycarbamide twice a day every day for 12 months * Visit the clinic at screening, baseline, 1, 3, 6, 9 and 12 months
Interventions
DRUGHydroxycarbamid
Hydroxycarbamide Paediatric dispersible tablets will be provided in the form of film-coated dispersible tablets containing 50 mg of hydroxycarbamide. The IMP will be administered as half-strength twice daily, based on the body weight of the patient.
Sponsors
Theravia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Months to 11 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent, signed and dated by both parents or by the legally acceptable representative(s) of the children, and, if possible, assent from the children, * HbSS or HbSβ0 SCD, * Aged between 9 months and 11 years old, * Hydroxycarbamide naïve, * Parent(s) or legally acceptable representative(s) capable of communicating with the investigator and understanding the requirements and constraints of the study protocol and willing to comply with the study requirements, * Contraception criterion, if applicable: for patients who are sexually active * Affiliated to a social security plan or beneficiary of a similar insurance plan, * Patient must meet the following laboratory values : Absolute Neutrophil Count ≥ 1.0x109/L, Platelets ≥ 75x109/L and Haemoglobin (Hgb) \> 5.5 g/dL, * Transcranial Doppler (TCD) in the last 12 months indicating low risk for stroke is required for children over 18 months of age.
Exclusion criteria
* Participation in any other clinical study for any other pharmaceutical product within 4 weeks preceding the inclusion visit, * Patients who have had chronic blood transfusion or transfusion in the last 3 months preceding the inclusion visit, * Patients treated with other SCD-modifying therapies, * Patient with a stage 3, 4 or 5 chronic kidney disease, * Patients known to be infected with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus, * Known hypersensitivity or allergy to the excipients, * Any surgical or medical condition or any significant illness that, in the opinion of the investigator, constitutes a risk or a contraindication to the participation of the patient to the study, or that may interfere with the objectives, conduct or evaluation of the study, * Female patients who are pregnant or lactating, * Any documented history of a clinical stroke or intracranial haemorrhage, or an uninvestigated neurologic finding within the past 12 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate the PK exposure for Hydroxycarbamide Paediatric dispersible tablets administered BID through area under the curve (AUC) | 1, 3, 6, 9 and 12 months after treatment initiation |
| Evaluate the PK exposure for Hydroxycarbamide Paediatric dispersible tablets administered BID through time to obtain the maximum concentration (Tmax) | 1, 3, 6, 9 and 12 months after treatment initiation |
| Evaluate the PK exposure for Hydroxycarbamide Paediatric dispersible tablets administered BID through maximum plasma concentration (Cmax) | 1, 3, 6, 9 and 12 months after treatment initiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute mean change from baseline in HbF levels | Baseline, 3, 6, 9 and 12 months after treatment initiation | — |
| HC plasma concentrations and HbF levels | Baseline, 3, 6, 9 and 12 months after treatment initiation | — |
| Daily AUC (AUC0-24h) at maintenance dose derived from the final PPK model | Baseline, 3, 6, 9 and 12 months after treatment initiation | — |
| Proportion of patients with a relative difference in Cmax ≥ 30% from BID maintenance dose relative to the one simulated on a once daily regimen giving an equivalent AUC0-24h. | Baseline, 3, 6, 9 and 12 months after treatment initiation | — |
| Absolute mean change from baseline in haematological parameters | Baseline,1, 3, 6, 9 and 12 months after treatment initiation | — |
| Acceptability score based on a hedonic face scale evaluated by the child from 3 years old | 3 months after treatment initiation | — |
| Acceptability score based on a 5-point Likert scale evaluated by the parent(s) or legally acceptable representative(s) | 3 months after treatment initiation | — |
| Distribution of the scores related to the ease of using the administration kit for treatment administration to the child based on a 5-point Likert scale evaluated by the parent(s) or legally acceptable representative(s) | 3 months after treatment initiation | Score 1 : very difficult to score 5 : very easy |
| Compliance with Hydroxycarbamide Paediatric dispersible tablets administered BID by treatment unit accountability calculated by the pharmacy (patient will bring the kits with used and unused bottles to the pharmacy at each visit) | Baseline, 1, 3, 6, 9, 12 months after treatment initiation | — |
| Number of SCD events occurring during the study | Baseline, 1, 3, 6, 9, 12 months after treatment initiation | — |
| Number of adverse events (AEs) and percentage of patients reporting at least one AE | Baseline, 1, 3, 6, 9, 12 months after treatment initiation | — |
Countries
France, French Guiana
Contacts
Primary ContactLaura Thomas-bourgneuf
Backup ContactNesrine Flissi
Outcome results
None listed