Clinical trial NCT06923111: PASS of Xromi Comparing Safety and Effectiveness in Children Under 2 Years With Sickle Cell Disease [PRECISE PASS]
Official title: A Comparative Observational Study to Evaluate the Safety and Effectiveness of Xromi (Hydroxycarbamide Oral Solution 100mg/ml) for the Prevention of Vaso-occlusive Complications of Sickle Cell Disease in Children Under 2 Years of Age.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sickle Cell Disease
Keywords: Hydroxyurea
liquid formulation
HbS Disease
Hemoglobin S Disease
Sickle Cell Anemia
Sickle Cell Disease
Sickle Cell Disorders
Sickling Disorder Due to Hemoglobin S
Xromi
Hydroxycarbamide
paediatric
children
hemaglobinopathy in children
hemoglobinopathy
paediatric formuation
Lead sponsor: Nova Laboratories Limited
Sponsor class: INDUSTRY
Collaborators: name: OXON Epidemiology
First posted: 2025-04-11
Enrollment: 180
Sex: ALL
Minimum age (years): 9
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist of children with SCD who meet all the inclusion criteria and none of the exclusion criteria.

Identification of participants will be conducted as follows:

* Prospective exposure cohort: Potential participants will be identified as they attend the participating sites where eligibility criteria will be assessed prior to initiation with Xromi.
* Retrospective comparator cohort: Potential participants will be selected from clinical chart review for hydroxycarbamide naive children that could be matched to prospective participants.

Brief summary: This post-authorisation safety and efficacy study (PRECISE PASS) evaluates the use of Xromi® (hydroxycarbamide 100 mg/mL oral solution) in children aged 9 months to under 2 years with sickle cell disease (SCD).

The objective is to assess the safety profile and clinical effectiveness of Xromi® under routine clinical conditions. The study includes a prospective cohort of Xromi®-treated patients and a matched retrospective comparator cohort of untreated patients. Participants will be followed for 24 months from treatment initiation or matched index date.

Detailed description: The PRECISE study is a combined Post-Authorisation Safety Study (PASS) (Category 3) and a Post-Authorisation Efficacy Study that aims to provide data on the safety and effectiveness of hydroxycarbamide 100mg/ml oral solution (Xromi ®) administered prospectively to children under 2 years of age, over a follow-up period of 24 months compared to matched retrospective comparators who were treatment naïve.

This is a non-interventional, matched cohort study involving children with SCD aged 9 to under 24 months. The study comprises two groups:

* A prospective Xromi®-exposed cohort, enrolled at the time of treatment initiation and followed for 24 months.
* A retrospective comparator cohort, matched 2:1 by site, age, and β-globin genotype, identified from clinical records of children not treated with hydroxycarbamide at the index date.

The primary objective is to compare the incidence of adverse events of special interest (AESIs) between the two cohorts. Secondary analyses will assess the comparative effectiveness of Xromi® on clinical events, laboratory parameters, and physiological assessments. Exploratory analyses will examine treatment-related safety and effectiveness by dose, subgroups, and exposure to hydroxycarbamide during follow-up.

Data will be sourced from routine clinical practice through chart reviews and follow-up visits. No study-specific interventions will be introduced. The study is planned across specialist sites in the UK and Germany, with potential expansion to other European countries if recruitment targets require.

Eligibility criteria: Prospective Exposure Cohort

* Inclusion criteria:

  * Aged from 9 months to under 2 years at the index date.
  * Diagnosis of SCD.
  * Known β-globin genotype at the index date.
  * Prescribed Xromi® for the prevention of complications of SCD.
  * Parent(s) (or a legal representative(s)) provides written informed consent to participate in the study, unless there is a waiver, non-opposition, or blanket written informed consent by the parent for research studies.
* Exclusion criteria:

  * Previous use of hydroxycarbamide of any formulation before the index date.
  * Receiving regular blood transfusions (occurring every 8 weeks or more frequently) at the index date.
  * Known hypersensitivity to any of the excipients of Xromi® at the index date.
  * Contraindications to the drug at the index date: severe hepatic impairment (Child-Pugh classification C); severe renal impairment (creatinine clearance: CrCl \<30 ml/min); presence of at least one of the following: Absolute neutrophil count (ANC) \< 1.0 x 10\^9/L, absolute reticulocyte count (ARC) \<80 x 10\^9/L, platelets \<80 x 10\^9/L.
  * Participating in another clinical study of an investigational medicinal product (IMP) at the index date.
  * Anti-retroviral medicinal products for human immunodeficiency virus (HIV) at the index date.
  * Active malignancy at the index date.

Participants in the prospective exposure cohort who are prescribed Xromi® but do not initiate treatment will be excluded from the dataset.

Retrospective Comparator cohort

* Inclusion criteria:

  * Aged from 9 months to under 2 years at the index date.
  * Diagnosis of SCD.
  * Known β-globin genotype.
  * Matched to an exposed participant.
  * Parent(s) (or a legal representative(s)) provides written informed consent to participate in the study, unless there is a waiver, non-opposition, or blanket written informed consent by the parent for research studies.
* Exclusion criteria:

  * Use of hydroxycarbamide of any formulation before or at the index date.
  * Receiving regular blood transfusions (occurring every 8 weeks or more frequently) at the index date.
  * Presence at the index date of any of the following: severe hepatic impairment (Child-Pugh classification C); severe renal impairment (CrCl \<30 ml/min); presence of at least one of the following: ANC \< 1.0 x 10\^9/L, ARC \< 80 x 10\^9/L, platelets \< 80 x 10\^9/L).
  * Participating in another clinical study of an IMP at the index date.
  * Anti-retroviral medicinal products for HIV at the index date.
  * Active malignancy at the index date.

Primary outcomes:
measure: AESI - Myelosuppression (Neutropenia)
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Myelosuppression (Reticulocytopenia)
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Myelosuppression (Thrombocytopenia)
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Myelosuppression (Anaemia)
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Abnormal Weight Gain
timeFrame: Baseline to 24 months
measure: AESI - Abnormal Weight Loss
timeFrame: Baseline to 24 months
measure: AESI - Increase in Hepatic Enzyme (ALT)
timeFrame: Baseline to 24 months
measure: AESI - Increase in Hepatic Enzyme (AST)
timeFrame: Baseline to 24 months
measure: AESI - Alopecia
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Other Hair Loss
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Skin Hyperpigmentation
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Rash
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Skin Ulcers
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Growth Retardation
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Bacterial Infection
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Viral Infection
timeFrame: Pre-baseline, Baseline to 24 months
measure: AESI - Fungal Infection
timeFrame: Pre-baseline, Baseline to 24 months
Secondary outcomes:
measure: Other Adverse Events
timeFrame: Baseline to 24 months
measure: Painful Vaso-occlusive Crisis (VOC)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Acute Chest Syndrome (ACS)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Splenomegaly
timeFrame: Pre-baseline, Baseline to 24 months
measure: Priapism
timeFrame: Baseline to 24 months
measure: Hepatobiliary disorder
timeFrame: Pre-baseline, Baseline to 24 months
measure: Splenic Sequestration Crisis
timeFrame: Pre-baseline, Baseline to 24 months
measure: Surgery
timeFrame: Pre-baseline, Baseline to 24 months
measure: Blood Transfusion
timeFrame: Pre-baseline, Baseline to 24 months
measure: Cerebrovascular accident
timeFrame: Pre-baseline, Baseline to 24 months
measure: Abnormal or Conditional TCD
timeFrame: Pre-baseline, Baseline to 24 months
measure: Hospitalisations for SCD
timeFrame: Pre-baseline, Baseline to 24 months
measure: Non-hospitalised Visit for SCD
timeFrame: Pre-baseline, Baseline to 24 months
measure: Other Clinical Events
timeFrame: Pre-baseline, Baseline to 24 months
measure: Other Event - Death
timeFrame: Baseline to 24 months
measure: Haemoglobin (Hb)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Foetal Haemoglobin (HbF)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Haemoglobin Fractions
timeFrame: Pre-baseline, Baseline to 24 months
measure: Absolute Neutrophil Count (ANC)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Absolute Reticulocyte Count (ARC)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Platelet Count
timeFrame: Pre-baseline, Baseline to 24 months
measure: White Blood Cell Count (WBC)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Mean Corpuscular Volume (MCV)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Mean Corpuscular Haemoglobin (MCH)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Ferritin
timeFrame: Pre-baseline, Baseline to 24 months
measure: Transferrin Saturation
timeFrame: Pre-baseline, Baseline to 24 months
measure: Alanine Transaminase (ALT)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Alkaline Phosphatase (ALP)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Aspartate Transaminase (AST)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Total Bilirubin
timeFrame: Pre-baseline, Baseline to 24 months
measure: Lactate Dehydrogenase
timeFrame: Pre-baseline, Baseline to 24 months
measure: Gamma-Glutamyl Transferase (GGT)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Serum Creatinine
timeFrame: Pre-baseline, Baseline to 24 months
measure: Estimated Glomular Filtration Rate (eGFR)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Albumin-Creatinine Ratio (ACR)
timeFrame: Pre-baseline, Baseline to 24 months
measure: Liver Size
timeFrame: Pre-baseline, Baseline to 24 months
measure: Spleen Size
timeFrame: Pre-baseline, Baseline to 24 months
measure: Maximum Time Averaged Mean Velocity (TAMV)
timeFrame: Pre-baseline, Baseline to 24 months
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
state: Essex
city: Cardiff
country: United Kingdom
facility: Noah's Ark Children's Hospital for Wales
state: Leicestershire
city: London
country: United Kingdom
facility: University College London Hospital
state: North London
city: London
country: United Kingdom
facility: The Royal London Hospital
state: Whitechapel
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Nova Laboratories Ltd.
name: Hussain Dr Mulla, PhD
role: STUDY_DIRECTOR
affiliation: University College London Hospitals
name: Sara Dr Trompeter, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rankine-Mullings A, Keenan R, Chakravorty S, Inusa B, Telfer P, Velangi M, Ware RE, Moss JJ, Lloyd AL, Edwards S, Mulla H. Efficacy, safety, and pharmacokinetics of a new, ready-to-use, liquid hydroxyurea in children with sickle cell anemia. Blood Adv. 2023 Aug 22;7(16):4319-4322. doi: 10.1182/bloodadvances.2023010099. No abstract available.
citation: Thompson BW, Miller ST, Rogers ZR, Rees RC, Ware RE, Waclawiw MA, Iyer RV, Casella JF, Luchtman-Jones L, Rana S, Thornburg CD, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik S, Howard TH, Luck L, Wang WC. The pediatric hydroxyurea phase III clinical trial (BABY HUG): challenges of study design. Pediatr Blood Cancer. 2010 Feb;54(2):250-5. doi: 10.1002/pbc.22269.