Etavopivat: Participants will receive oral tablets or granules of etavopivat once daily.
Study summary
The purpose of this study is to evaluate the pharmacokinetics and safety of etavopivat in paediatric participants with sickle cell disease (SCD). Participants will receive etavopivat and will be enrolled in a staggered manner, starting with the oldest age group and followed sequentially by younger cohorts after review of pharmacokinetic and safety data from the preceding cohort. All participants will undergo a 24-week primary treatment period followed by a 72-week extension treatment period to further evaluate long-term safety and pharmacokinetics of etavopivat. The total duration of the study will be approximately 96 weeks.
Eligibility
Sex
ALL
Min age
6 Months
Max age
18 Years
Healthy volunteers
No
Inclusion Criteria:
* Type of Participant and Disease Characteristics
1. Patient's parent, legal guardian, or legal representative has provided documented informed consent and patients have provided age-appropriate assent
2. Age greater than or equal to (≥) 6 months and lesser than (\<) 18 years of age at time of enrollment, according to the enrolling cohort:
* Cohort 1: age 12 to \< 18 years (adolescents)
* Cohort 2: age 6 to \< 12 years
* Cohort 3: age 2 to \< 6 years
* Cohort 4: age 6 months to \< 2 years
3. Patient has confirmed diagnosis of SCD
• Documentation of SCD genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing. Molecular genotyping is not required. SCD genotype may be determined from the results of Hb electrophoresis, high-performance liquid chromatography (HPLC), or similar testing. Note that Hb electrophoresis is performed by the local laboratory at Screening.
4. Hemoglobin ≥ 5.5 and lesser than or equal to (≤) 10.5 grams per deciliter (g/dL)
5. Pediatric patients with severe SCD, as defined by at least 1 of the following:
* 2-15 episodes of documented VOC within the 12 months prior to screening. Documentation must exist in the patient's medical record prior to screening. Events based solely on patient recall without supporting documentation should not be counted towards eligibility.
* Hospitalization for any SCD-related complication in the last 12 months prior to starting study treatment
* Proteinuria, defined as an albumin:creatinine ratio (ACR) \> 100 mg/g on 2 measures (separated by ≥ 1 month) as an indicator of early renal disease
* History of a conditional TCD in the last 12 months prior to starting study treatment, but not currently being treated with chronic transfusion therapy (applicable to participants \> 2 years of age). Conditional TCD is defined as a TAMMV of 170-199 cm/s by TCD or 155-184 cm/s by imaging TCD (TCDi).
6. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study, in the opinion of the Investigator
7. Patients on crizanlizumab or L-glutamine treatment at the time of consent may be eligible if they:
* Have been on a stable dose for ≥ 12 months at the time of consent (ie, no changes to the dose except for changes to weight or for safety reasons)
* For patients on crizanlizumab, have been ≥ 80% compliant with the planned regimen during the 12 months prior to the time of consent
8. Female patients of childbearing potential who are using acceptable methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and male patients who are willing to use acceptable methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug.
Exclusion Criteria:
* Medical Conditions
1. Female who is breastfeeding or pregnant
2. More than 15 VOCs within the 12 months prior to starting study treatment that required a hospital, emergency room (ER), or clinic visit
3. Hospitalized for sickle cell crisis or other vaso-occlusive event occurring in the 14 days prior to starting study treatment
4. Abnormal TCD in the 12 months prior to starting study treatment
Prior/Concomitant Therapy
5. Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)
6. Received any blood products within 30 days of starting study treatment
7. Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4/5 within 2 weeks of starting study treatment
8. Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study
9. Receipt of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study
10. Receipt of prior cellular based therapy (eg, hematopoietic cell transplant, gene modification therapy)
Primary outcome measure(s)
Single-dose: maximum plasma concentration (Cmax) — During the 24-week primary treatment period
Single-dose: area under the plasma concentration time curve from dosing (time 0) to time t ((AUC)0-t) — During the 24-week primary treatment period
Single-dose: area under the plasma concentration time curve from zero to time infinity (AUC0-inf) — During the 24-week primary treatment period
Steady-state maximum plasma concentration (Cmax,ss) — During the 24-week primary treatment period
Steady-state area under the concentration time curve over the dosing interval (AUCtau,ss) — During the 24-week primary treatment period
Steady-state average plasma concentration (Cavg,ss) — During the 24-week primary treatment period
Steady-state minimum plasma concentration (Cmin,ss) — During the 24-week primary treatment period
Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs related to etavopivat — During the 24-week primary treatment period
Number of premature discontinuations — During the 24-week primary treatment period
Number of dose interruptions — During the 24-week primary treatment period
Number of dose reductions — During the 24-week primary treatment period
Trial sites (18)
Facility
City
Region
Status
The Hospital for Sick Children
Toronto
Ontario
Completed
HCL-HOPITAL LYON SUD_Institut d'Hématologie et d'Oncologie Pédiatrique (IHOPe)
Lyon
France
Not Yet Recruiting
APHP - Centre de Référence des Syndromes
Paris
France
Not Yet Recruiting
Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
Roeun
France
Not Yet Recruiting
KEMRI CRDR Siaya Clinical Research Annex, Country Referral Hospital
Siaya
Siaya County
Recruiting
KEMRI-Walter-Reed Kericho
Kericho
Kenya
Recruiting
Kombewa Clinical Research Centre
Kisumu
Kenya
Recruiting
Ahero Clinical Trials Unit
Kisumu
Kenya
Recruiting
American University of Beirut Medical center
Beirut
Lebanon
Recruiting
Hospital Nini
Tripoli
Lebanon
Recruiting
University of Nigeria Teaching Hospital (UNTH)
Ituku-Ozalla
Enugu State
Recruiting
Lagos University Teaching Hospital, Lagos
Lagos
Nigeria
Recruiting
Aminu Kano Teaching Hospital (AKTH)
Tarauni
Nigeria
Recruiting
Hacettepe University pediatric hematology
Ankara
Turkey (Türkiye)
Completed
Acıbadem Adana Hastanesi
Seyhan
Turkey (Türkiye)
Completed
Guys and St Thomas NHS Foundation Trust / Evelina Childrens Hospital
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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