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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Theravia

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

25 Mar 2026 → ongoing

Decision date (initial)

2024-08-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Theravia

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

The primary objective is to develop a population pharmacokinetic (PPK) model of Siklos® Paediatric dispersible tablets administered BID in children aged 9 months to 11 years.

Secondary objectives 10

1. To evaluate HbF levels at 3, 6, 9 and 12 months
2. To develop a population pharmacokinetic-pharmacodynamic (PPKPD) model for HbF
3. To assess the daily exposures obtained at maintenance dose with Siklos® Paediatric dispersible tablets administered BID
4. To assess Cmax reduction on twice-daily regimen compared to once-daily regimen with an equivalent area under the curve (AUC0-24h) at maintenance dose.
5. To evaluate other haematological parameters at 1, 3, 6, 9 and 12 months to monitor benefit risk ratio
6. To evaluate the acceptability of Siklos® Paediatric dispersible tablets administered BID
7. To evaluate the ease of using the administration kit, as reported by the parent(s) or legally acceptable representative(s)
8. To describe the compliance with Siklos® Paediatric dispersible tablets administered BID
9. To describe SCD events occurring during the study
10. To assess the safety profile of Siklos® Paediatric dispersible tablets administered BID

Conditions and MedDRA coding

Sickle Cell Disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003388-PIP01-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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
2. HbSS or HbSβ0 SCD
3. Aged between 9 months and 11 years old
4. HC-naïve (absence of previous or current treatment with HC)
5. 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
6. 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.
7. Affiliated to a social security plan (including universal health coverage) or beneficiary of a similar insurance plan
8. Patient must meet the following laboratory values : Absolute Neutrophil Count ≥ 1,0x109/L, Platelets ≥ 75x109/L and Haemoglobin (Hgb) > 5,5 g/dL
9. Transcranial Doppler (TCD) in the last 12 months indicating low risk for stroke is required for children over 18 months of age.

Exclusion criteria 9

1. Participation in any other clinical study for any other pharmaceutical product within 4 weeks preceding the inclusion visit
2. Patients who have had chronic blood transfusion or transfusion in the last 3 months preceding the inclusion visit
3. Patients treated with other SCD-modifying therapies
4. Patient with a stage 3, 4 or 5 chronic kidney disease (estimated glomerular filtration rate < 60 mL/min per 1.73 m2
5. Patients known to be infected with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
6. Known hypersensitivity or allergy to the excipients
7. 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
8. Female patients who are pregnant or lactating
9. Any documented history of a clinical stroke or intracranial haemorrhage, or an uninvestigated neurologic finding within the past 12 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 11

1. The absolute mean change from baseline in HbF levels at 3, 6, 9 and 12 months after treatment initiation
2. HC plasma concentrations and HbF levels recorded throughout study follow-up
3. Daily AUC (AUC0-24h) at maintenance dose derived from the final PPK model
4. Relative difference in Cmax ≥30% from BID maintenance dose relative to the one simulated on a once-daily regimen giving an equivalent AUC0-24h
5. 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
6. Acceptability score based on a hedonic face scale evaluated by the child from 3 years old, 3 months after treatment initiation
7. Acceptability score based on a 5-point Likert scale evaluated by the parent(s) or legally acceptable representative(s), 3 months after treatment initiation
8. 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
9. Compliance with Siklos® Paediatric dispersible tablets administered BID by treatment unit accountability from treatment initiation to month 12
10. Number of SCD events occurring during the study
11. Number of adverse events (AEs) and percentage of patients reporting at least one AE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Theravia

Sponsor organisation

Theravia

Address

16 Rue Montrosier

City

Neuilly Sur Seine

Postcode

92200

Country

France

Scientific contact point

Organisation

Theravia

Contact name

Laura Fabre Thomas-bourgneuf

Public contact point

Organisation

Theravia

Contact name

Laura Fabre Thomas-bourgneuf

Third parties 5

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications