Clinical trial NCT06578507: Pharmacokinetics, Efficacy and Safety of Twice Daily Dosing Regimen of Hydroxycarbamide Dispersible Tablets in Children With Sickle Cell Disease
Official title: Pharmacokinetics, Efficacy and Safety of Twice Daily Dosing Regimen of Hydroxycarbamide Dispersible Tablets in Children With Sickle Cell Disease: a Single-group, Non-randomised, Open-label Study (KID-BID)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: Hydroxycarbamide
Pharmacokinetic
Lead sponsor: Theravia
Sponsor class: INDUSTRY
First posted: 2024-08-29
Enrollment: 50
Sex: ALL
Minimum age (years): 9
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate the PK exposure for Hydroxycarbamide Paediatric dispersible tablets administered BID through area under the curve (AUC)
timeFrame: 1, 3, 6, 9 and 12 months after treatment initiation
measure: Evaluate the PK exposure for Hydroxycarbamide Paediatric dispersible tablets administered BID through time to obtain the maximum concentration (Tmax)
timeFrame: 1, 3, 6, 9 and 12 months after treatment initiation
measure: Evaluate the PK exposure for Hydroxycarbamide Paediatric dispersible tablets administered BID through maximum plasma concentration (Cmax)
timeFrame: 1, 3, 6, 9 and 12 months after treatment initiation
Secondary outcomes:
measure: Absolute mean change from baseline in HbF levels
timeFrame: Baseline, 3, 6, 9 and 12 months after treatment initiation
measure: HC plasma concentrations and HbF levels
timeFrame: Baseline, 3, 6, 9 and 12 months after treatment initiation
measure: Daily AUC (AUC0-24h) at maintenance dose derived from the final PPK model
timeFrame: Baseline, 3, 6, 9 and 12 months after treatment initiation
measure: 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.
timeFrame: Baseline, 3, 6, 9 and 12 months after treatment initiation
measure: Absolute mean change from baseline in haematological parameters
timeFrame: Baseline,1, 3, 6, 9 and 12 months after treatment initiation
measure: Acceptability score based on a hedonic face scale evaluated by the child from 3 years old
timeFrame: 3 months after treatment initiation
measure: Acceptability score based on a 5-point Likert scale evaluated by the parent(s) or legally acceptable representative(s)
timeFrame: 3 months after treatment initiation
measure: 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)
timeFrame: 3 months after treatment initiation
measure: 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)
timeFrame: Baseline, 1, 3, 6, 9, 12 months after treatment initiation
measure: Number of SCD events occurring during the study
timeFrame: Baseline, 1, 3, 6, 9, 12 months after treatment initiation
measure: Number of adverse events (AEs) and percentage of patients reporting at least one AE
timeFrame: Baseline, 1, 3, 6, 9, 12 months after treatment initiation
Other outcomes:
Locations:
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal Créteil
city: Jossigny
country: France
facility: GHEF- Site de Marne-la-Vallée
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
city: Lyon
country: France
facility: Institut d'Hématologie et d'oncologie pédiatrique - IHOPe
city: Paris
country: France
facility: Hôpital Necker-Enfants malades
city: Cayenne
country: French Guiana
facility: Centre hospitalier de Cayenne
Study officials:
affiliation: Hôpital Necker-Enfants Malades
name: Josephine Brice, MD
role: PRINCIPAL_INVESTIGATOR
References: