HYDROXYCARBAMIDE for Sickle Cell Disease

Inclusion criteria

• {"criterion_text":"- 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\n- HbSS or HbSβ0 SCD\n- Aged between 9 months and 11 years old\n- HC-naïve (absence of previous or current treatment with HC)\n- 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\n- Contraception criterion, if applicable: for patients who are sexually active Female patients of childbearing potential (post menarche) at screening agreeing to use a highly effective form of contraception (oral, injected or implanted hormonal contraception, intrauterine device, o abstinence) during the trial and for 3 months after HC discontinuation. Male patients with partners of childbearing potential agreeing to use a highly effective contraception during the trial and for 3 months after HC discontinuation. Male patients with pregnant or lactating partners should be advised to use a barrier method of contraception (condom) to prevent the foetus or breastfed infant from exposure to HC.\n- Affiliated to a social security plan (including universal health coverage) or beneficiary of a similar insurance plan\n- Patient must meet the following laboratory values : Absolute Neutrophil Count ≥ 1,0x109/L, Platelets ≥ 75x109/L and Haemoglobin (Hgb) > 5,5 g/dL\n- Transcranial Doppler (TCD) in the last 12 months indicating low risk for stroke is required for children over 18 months of age."}

Exclusion criteria

• {"criterion_text":"- Participation in any other clinical study for any other pharmaceutical product within 4 weeks preceding the inclusion visit\n- Patients who have had chronic blood transfusion or transfusion in the last 3 months preceding the inclusion visit\n- Patients treated with other SCD-modifying therapies\n- Patient with a stage 3, 4 or 5 chronic kidney disease (estimated glomerular filtration rate < 60 mL/min per 1.73 m2\n- Patients known to be infected with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus\n- Known hypersensitivity or allergy to the excipients\n- Any surgical or medical condition or any significant illness (of which severe hepatic impairment [Child-Pugh classification C], severe renal impairment, toxic ranges of myelosuppression) 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\n- Female patients who are pregnant or lactating\n- Any documented history of a clinical stroke or intracranial haemorrhage, or an uninvestigated neurologic finding within the past 12 months."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is to evaluate the PK exposure for Siklos® Paediatric dispersible tablets administered BID through area under the curve (AUC), time to obtain the maximum concentration (Tmax) and maximum plasma concentration (Cmax) at 1, 3, 6, 9 and 12 months after treatment initiation","definition_or_measurement_approach":"PK exposure measured by AUC, Tmax and Cmax at 1, 3, 6, 9 and 12 months after treatment initiation (population pharmacokinetic analysis)"}

Secondary endpoints

• {"endpoint_text":"- The absolute mean change from baseline in HbF levels at 3, 6, 9 and 12 months after treatment initiation","definition_or_measurement_approach":"Mean change from baseline in HbF levels measured at 3, 6, 9 and 12 months"}
• {"endpoint_text":"- HC plasma concentrations and HbF levels recorded throughout study follow-up","definition_or_measurement_approach":"Serial HC plasma concentration measurements and concurrent HbF level assessments throughout follow-up"}
• {"endpoint_text":"- Daily AUC (AUC0-24h) at maintenance dose derived from the final PPK model","definition_or_measurement_approach":"Daily AUC0-24h calculated from the final population PK model at maintenance dose"}
• {"endpoint_text":"- Relative difference in Cmax ≥30% from BID maintenance dose relative to the one simulated on a once-daily regimen giving an equivalent AUC0-24h","definition_or_measurement_approach":"Comparison of Cmax between BID maintenance dose and simulated once-daily regimen (equivalent AUC0-24h); assess relative difference ≥30%"}
• {"endpoint_text":"- The absolute mean change from baseline in haematological parameters (white blood cell, absolute neutrophil count, lymphocytes, monocytes, eosinophils, basophils, platelets, mean corpuscular volume, mean corpuscular haemoglobin concentration, mean corpuscular haemoglobin, haemoglobin, reticulocytes, red blood cell count) at 1, 3, 6, 9 and 12 months after treatment initiation","definition_or_measurement_approach":"Mean change from baseline for listed haematological parameters measured at 1, 3, 6, 9 and 12 months"}
• {"endpoint_text":"- Acceptability score based on a hedonic face scale evaluated by the child from 3 years old, 3 months after treatment initiation","definition_or_measurement_approach":"Child-reported hedonic face scale (from age 3) assessed at 3 months"}
• {"endpoint_text":"- Acceptability score based on a 5-point Likert scale evaluated by the parent(s) or legally acceptable representative(s), 3 months after treatment initiation","definition_or_measurement_approach":"Parent/legal representative 5-point Likert acceptability score at 3 months"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Distribution of parent/legal representative responses on 5-point Likert scale regarding ease of using administration kit at 3 months"}
• {"endpoint_text":"- Compliance with Siklos® Paediatric dispersible tablets administered BID by treatment unit accountability from treatment initiation to month 12","definition_or_measurement_approach":"Treatment unit accountability records used to assess compliance from initiation through 12 months"}
• {"endpoint_text":"- Number of SCD events occurring during the study","definition_or_measurement_approach":"Count of sickle cell disease related events occurring during study follow-up"}
• {"endpoint_text":"- Number of adverse events (AEs) and percentage of patients reporting at least one AE","definition_or_measurement_approach":"Number and proportion of patients reporting any adverse event; standard AE reporting"}

France

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

639

Number Of Sites

7

Number Of Participants

50

Primary sponsor

Full Name

Theravia

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"TrialPEX","duties_or_roles":"Patients reimbursements for travels/meals/external laboratory","organisation_type":"Industry"}
• {"country":"France","full_name":"Hopital Necker Enfants Malades","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Keyrus","duties_or_roles":"1,10,11,12,5,6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Hôpital Cochin","duties_or_roles":"4","organisation_type":"Educational Institution"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}