Sickle Cell DiseasePhase 1HESTIA4NCT03492931
PK Study of Ticagrelor in Children Aged Less Than 24 Months, With Sickle Cell Disease (HESTIA4)
A Phase 1 study testing Ticagrelor in people with Sickle Cell Disease, run by AstraZeneca at 8 sites in 6 countries.
Trial summary
The purpose of this Phase I study is to investigate the pharmacokinetic properties of ticagrelor in pediatric patients from 0 to less than 24 months with sickle cell disease. Ticagrelor dose level adjustment will require a Protocol amendment and regulatory approval. Read more about this study
- Who is it for?
- Ages 1 day to 23 months
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Ticagrelor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 8 sitesin 6 countries
- Study dates
- 28 Mar 2018to 7 May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 23 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Paediatric patients aged <24 months, diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassemia (HbS/β0), as confirmed by high performance liquid chromatography or haemoglobin electrophoresis.
- Body weight ≥5 kg at the time of screening.
- If treated with an anti-sickling agent such as hydroxyurea, the weight-adjusted dose must be stable for 3 months before screening/enrolment.
- Provision of signed and dated written informed consent from parents/legal guardians prior to any study specific procedures not part of standard medical care.
Who cannot join
- History of transient ischaemic attack or cerebrovascular event/accident (ischaemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy.
- Significantly underdeveloped with regards to height, weight or head circumference for age, as judged by the Investigator.
- Severe developmental delay (eg, cerebral palsy or mental retardation).
- Receiving chronic treatment (>3 days/week) with non-steroidal anti-inflammatory drugs (NSAIDs).
- Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.
- Moderate or severe hepatic impairment, defined as laboratory values of alanine aminotransferase (ALT) >2 × upper limit of normal (ULN), total bilirubin >2 × ULN (unless judged by the Investigator to be caused by haemolysis), albumin <35 g/L and international normalised ratio (INR) >1.4, or symptoms of liver disease (eg, ascites).
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- Renal failure requiring dialysis.
- Active pathological bleeding or increased risk of bleeding complications according to the Investigator.
- Haemoglobin <6 g/dL from test performed at Screening (Visit 1).
- Platelets <100 × 10^9/L from test performed at Screening (Visit 1).
- Patient considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second or third degree atrioventricular block).
- Concomitant oral or intravenous therapy with moderate or strong CYP3A4 inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers that have not been stopped at least 5 half-lives before dose administration.
- Patient breastfed by mother who is under treatment of strong CYP3A4 inhibitors,
- Active untreated malaria. Patients with suspected malaria at Screening (Visit 1) will be tested.
- Surgical procedure planned to occur during the study including 5 days after ticagrelor administration.
- Known hypersensitivity or contraindication to ticagrelor.
- Concern for the inability of the patient or parents to comply with study procedures and/or follow-up.
- Any condition which, in the opinion of the Investigator, would make it unsafe or unsuitable for the patient to participate in this study.
- Previously administered ticagrelor in the present study.
- Participation in another clinical study with an investigational medicinal product (IMP) or device during the last 30 days preceding screening/enrolment.
- Involvement of member of patient's family in planning and/or conduct of the study (applies to both AstraZeneca personnel and personnel at study centre).
Trial locations and contacts
8 sites in 6 countries.
8 sites in 6 countries
About this study
Official title: A Multi-centre, Phase I, Open-label, Single-dose Study to Investigate Pharmacokinetics (PK) of Ticagrelor in Infants and Toddlers, Aged 0 to Less Than 24 Months, With Sickle Cell Disease (HESTIA4)
The purpose of this Phase I study is to investigate the pharmacokinetic properties of ticagrelor in pediatric patients from 0 to less than 24 months with sickle cell disease.
Ticagrelor dose level adjustment will require a Protocol amendment and regulatory approval.
Read the detailed description
Study design This Phase I paediatric study (in patients aged 0 to <24 months) with ticagrelor is planned to be a multi-centre, open-label, single dose study.
Primary Objective:
To determine the PK properties of ticagrelor after a single oral dose
Secondary Objectives:
To determine the PK properties of the active metabolite (AR-C124910XX) after a single oral dose To assess the acceptability and the palatability of a single oral dose of ticagrelor
Safety Objective:
To assess safety and tolerability of a single oral dose of ticagrelor
Duration of treatment At least 20 eligible patients will receive a single open label oral dose of ticagrelor on Day 1.
Statistical methods A population PK analysis approach will be used to determine the PK parameters of ticagrelor and its metabolite AR-C124910XX in paediatric patients aged 0 to <24 months eg, CL/F (oral clearance) (only for ticagrelor) and AUC.
The PK will also be described by presenting the observed plasma concentrations of Ticagrelor and its active metabolite for all individuals, as well as corresponding descriptive statistics.
No statistical comparisons are planned for the primary or secondary objectives, which will be summarised descriptively
- Conditions
- Sickle Cell Disease
- Being tested
- Ticagrelor
- Keywords
- Hb SS disease, Hb S Beta 0 Thalassemia
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
Also called AR-C124910XX is an active metabolite of ticagrelor given orally in a single dose. It will be measured, but it won't be given directly to subjects.
Patients will receive a single dose of ticagrelor
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Single dose of ticagrelor based on age Receives: Drug: Ticagrelor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Plasma Concentration (Cmax) of Ticagrelor
This measure is obtained from observed plasma concentrations
Measured: 1,2,4,6 hours post dose
Area under plasma concentration curve
This measure is obtained from the population PK analysis
Measured: 1,2,4,6 hours post dose
CL/F (Oral clearance)
This measure is obtained from the population PK analysis.
Measured: 1,2,4,6 hours post dose
Secondary outcomes (3)
Peak Plasma Concentration (Cmax) for active metabolite (AR-C124910XX)
Measured: 1,2,4,6 hours post dose
Area under plasma concentration curve
Measured: 1,2,4,6 hours post dose
Assessment of ticagrelor suspension for palatability
Questionnaire with one five-options question reflecting different degrees of patients willingness to swallow, from "swallowed without problem" to "vomited up medication".
Measured: Day 1, single timepoint assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2018
- Study start28 Mar 2018
- Primary completion7 May 2019
- Study completion7 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03492931
- Sponsor's protocol ID
- D5136C00010
- Acronym
- HESTIA4
- Status last verified
- May 2021
- First submitted
- 16 Mar 2018
- Last updated
- 10 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Duniva Inusa BP, Inati A, Maes P, Githanga J, Ogutu B, Abboud MR, Miano M, Cela E, Nduba V, Niazi M, Astrand M, Persson K, Berggren A, Carlson G. Pharmacokinetics and safety of ticagrelor in infants and toddlers with sickle cell disease aged <24 months. Pediatr Blood Cancer. 2021 May;68(5):e28977. doi: 10.1002/pbc.28977. Epub 2021 Feb 25.
PubMed 33629819
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Phase I, Open-label, Single-dose Study to Investigate Pharmacokinetics (PK) of Ticagrelor in Infants and Toddlers, Aged 0 to Less Than 24 Months, With Sickle Cell Disease (HESTIA4)
- ClinicalTrials.gov ID
- NCT03492931
- Acronym / sponsor ID
- HESTIA4 / D5136C00010
- Conditions
- Sickle Cell Disease
- Keywords
- Hb SS disease, Hb S Beta 0 Thalassemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 28 Mar 2018 (actual)
- Primary completion
- 7 May 2019 (actual)
- Study completion
- 7 May 2019 (actual)
- First posted
- 10 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase I study is to investigate the pharmacokinetic properties of ticagrelor in pediatric patients from 0 to less than 24 months with sickle cell disease.
Ticagrelor dose level adjustment will require a Protocol amendment and regulatory approval.
Detailed description
Study design This Phase I paediatric study (in patients aged 0 to <24 months) with ticagrelor is planned to be a multi-centre, open-label, single dose study.
Primary Objective:
To determine the PK properties of ticagrelor after a single oral dose
Secondary Objectives:
To determine the PK properties of the active metabolite (AR-C124910XX) after a single oral dose To assess the acceptability and the palatability of a single oral dose of ticagrelor
Safety Objective:
To assess safety and tolerability of a single oral dose of ticagrelor
Duration of treatment At least 20 eligible patients will receive a single open label oral dose of ticagrelor on Day 1.
Statistical methods A population PK analysis approach will be used to determine the PK parameters of ticagrelor and its metabolite AR-C124910XX in paediatric patients aged 0 to <24 months eg, CL/F (oral clearance) (only for ticagrelor) and AUC.
The PK will also be described by presenting the observed plasma concentrations of Ticagrelor and its active metabolite for all individuals, as well as corresponding descriptive statistics.
No statistical comparisons are planned for the primary or secondary objectives, which will be summarised descriptively
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: TicagrelorSingle dose of ticagrelor based on age |
Who may qualify
- Ages
- 1 day to 23 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Paediatric patients aged <24 months, diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassemia (HbS/β0), as confirmed by high performance liquid chromatography or haemoglobin electrophoresis.
- Body weight ≥5 kg at the time of screening.
- If treated with an anti-sickling agent such as hydroxyurea, the weight-adjusted dose must be stable for 3 months before screening/enrolment.
- Provision of signed and dated written informed consent from parents/legal guardians prior to any study specific procedures not part of standard medical care.
Key exclusion criteria (21 listed)
- History of transient ischaemic attack or cerebrovascular event/accident (ischaemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy.
- Significantly underdeveloped with regards to height, weight or head circumference for age, as judged by the Investigator.
- Severe developmental delay (eg, cerebral palsy or mental retardation).
- Receiving chronic treatment (>3 days/week) with non-steroidal anti-inflammatory drugs (NSAIDs).
- Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TicagrelorAlso: AR-C124910XX is an active metabolite of ticagrelor given orally in a single dose. It will be measured, but it won't be given directly to subjects.Patients will receive a single dose of ticagrelor | Drug | Treatment arm |
Primary outcome
Peak Plasma Concentration (Cmax) of Ticagrelor
Time frame: 1,2,4,6 hours post dose
This measure is obtained from observed plasma concentrations
Area under plasma concentration curve
Time frame: 1,2,4,6 hours post dose
This measure is obtained from the population PK analysis
CL/F (Oral clearance)
Time frame: 1,2,4,6 hours post dose
This measure is obtained from the population PK analysis.
3 secondary outcomes
Peak Plasma Concentration (Cmax) for active metabolite (AR-C124910XX)
Time frame: 1,2,4,6 hours post dose
Area under plasma concentration curve
Time frame: 1,2,4,6 hours post dose
Assessment of ticagrelor suspension for palatability
Time frame: Day 1, single timepoint assessment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2021.
- Derived from this study: PubMed 33629819Duniva Inusa BP, Inati A, Maes P, Githanga J, Ogutu B, Abboud MR, Miano M, Cela E, Nduba V, Niazi M, Astrand M, Persson K, Berggren A, Carlson G. Pharmacokinetics and safety of ticagrelor in infants and toddlers with sickle cell disease aged <24 months. Pediatr Blood Cancer. 2021 May;68(5):e28977. doi: 10.1002/pbc.28977. Epub 2021 Feb 25.
- Study results information posted to AstraZeneca Cinical Trials WebisteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ticagrelor in people with Sickle Cell Disease, run by AstraZeneca at 8 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Kenya, Lebanon, Belgium, Italy, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Plasma Concentration (Cmax) of Ticagrelor (time frame: 1,2,4,6 hours post dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03492931, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2021.