Optimization of the management of drepanocytosis patients treated with hydroxyurea: Interest of the pharmacological therapeutic follow-up

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

19 Jul 2024 → 27 Oct 2025

Decision date (initial)

2024-07-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515562-14-00

EudraCT number

2021-002094-26

ClinicalTrials.gov

NCT06464458

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

Compare the time to reach DMT in 2 groups of patients each with a
different methodology of therapeutic follow-up

Secondary objectives 5

1. Evaluate the clinical effectiveness of HU treatment according to management strategy
2. Evaluate the toxicity of HU treatment according to the management strategy
3. Conduct a pharmacokinetic/pharmacodynamic study of hydroxyurea in a paediatric and adult population
4. Establish a population pharmacokinetics database and identify the parameters involved in the pharmacokinetic variability of hu to better predict individual dose adjustment from our population study.
5. Confirm the merits of reducing the number of samples in children, but also in adults, by demonstrating that a single sample at time (T = 2 hours) is sufficient to predict exposure to the drug and allow dosage adjustment.

Conditions and MedDRA coding

Drepanocytosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Subject of age between 2 and 35 years.
2. Sickle cell genotype: HbSS
3. Subject who has been hospitalized for CVO in the last 3 months in whom hu treatment is to be initiated and / or whose treatment is not balanced or less than 30 mg / kg regardless of the age of treatment
4. For a woman of childbearing age: o Negative blood pregnancy test at inclusion visit o Patient accepting highly effective contraception for the duration of participation in the study and 182 days after discontinuation of the study or treatment for a woman. The contraceptives considered highly effective are: ▪ Combined hormonal contraception (containing estrogen and progesterone) associated with ovulation inhibition: oral, intravaginal, transdermal ▪ Hormonal contraception progesterone alone associated with ovulation inhibition: oral, injectable, implantable ▪ intrauterine device ▪ intrauterine device with hormone release ▪ tubal ligation
5. For men of childbearing age: patient accepting effective contraception throughout the study and for 92 days after stopping the study or treatment, use of condoms in the included patient as well as taking contraception by the partner of childbearing age.
6. Initiation of HU treatment in a patient requiring therapeutic intensification in the context of sickle cell disease
7. Hospitalized patient (e.g. vaso-occlusive crisis) and / or whose treatment with HU is unbalanced (DMT not reached)
8. Subject affiliated to a social protection scheme for health insurance or beneficiary
9. Subject who has been informed of the results of the prior medical examination, and/or whose holder(s) of parental authority has been informed(s)
10. Subject able to understand the objectives and risks related to the research and to give dated and signed informed conse
11. Informed consent signed as the case may be, by: o the patient and/or o the holder(s) of parental authority and the minor subject if he is capable of discernment

Exclusion criteria 16

1. Patient treated with HU who has reached DMT (hematological criteria) or who does not have therapeutic ineffectiveness or hydroxyurea dosage > 350 mg / kg / day.
2. Inability to give informed information about (subject in emergency situation)
3. Concomitant inclusion in another drug study
4. Subject under safeguard of justice
5. Impossibility for the subject to submit to the medical follow-up of the trial for geographical, social or psychological reasons
6. Subject under guardianship or curatorship
7. Pregnancy or breastfeeding in progress for teenagers or adults
8. Refusal to agree to use a highly effective contraceptive method as defined during a HU treatment and during the 182 days for women and 92 days for men following this treatment (fertile patients only).
9. Patient with a parental project within 18 months
10. Hypersensitivity to the active substance or to any of the excipients of the drug.
11. Severe hepatic impairment.
12. Severe renal failure.
13. Toxic signs of myelosuppression o Neutrophils < 1,500/mm3 o Platelets < 80,000/mm3 o Hemoglobin < 4.5 g/dL o Reticulocytes < 80,000/mm3 if the haemoglobin concentration is < 9 g/dL
14. Patient who received a transfusion, transfusion exchanges or administration of erythropoietin within 3 months before inclusion
15. Subject in period of exclusion (determined by a previous or ongoing study)
16. HIV-positive patient

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects with a time to reach LMA of less than 9 months

Secondary endpoints 5

1. Clinical parameters of efficacy in both arms: has. a. Number of vaso-occlusive seizures b. Number of complications related to sickle cell disease and/or hydroxyurea c. Number of hospitalizations d. Time elapsed before the need for transfusion e. Percentage of HbF
2. Biological parameters of toxicity in both arms: has. a. Complete blood count, reticulocytes, ferritin b. Renal function (glomerular filtration rate estimated by cystatin C, plasma creatinine and urea) c. Liver function (AST, ALT, total and conjugated bilirubin).
3. Non-compliance parameters: has. a. Mean blood cell volume (MCV) b. Percentage of HbF
4. Population pharmacokinetic parameters of the 2 arms: a. AUC b. Clearance and volume of distribution of the drug.
5. Pharmacokinetic analysis: has. a. Pharmacokinetic modeling of the population and identification of parameters involved in the inter- and intra-individual variability of the pharmacokinetics of the HU and allowing to better predict the individual dosage adaptation from our population study: i. Renal function ii. Age iii. Weight iv. Body surface v. % HbF b.Correlation between the concentrations obtained at the different sampling times and the AUC

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Place De L Hopital, Cs 80426 Cs 80426

City

Strasbourg Cedex

Postcode

67091

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Paillard

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Paillard

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

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

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