PASS of Xromi Comparing Safety and Effectiveness in Children Under 2 Years With Sickle Cell Disease [PRECISE PASS]

Nova Laboratories

Status: Enrolling

Conditions: Sickle Cell Disease

Treatments: Drug: Xromi

Study type: Observational

Funder types: Industry

Identifiers

NCT06923111

NOVDD-001

CHIL 62837 (Other Identifier)

334976 (Other Identifier)

EUPAS1000000076 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 estimated patients

Sex: All

Ages: 9 to 23 months old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

180 participants in 2 patient groups

Prospective Exposure Cohort

Description:

Children with SCD aged 9 months to under 2 years of age who are newly prescribed Xromi®, will be identified prospectively. These participants will be followed up for 24 months from their index date, regardless of whether they continue treatment with Xromi®, discontinue all hydroxycarbamide treatment, or switch to another formulation of hydroxycarbamide. The decision to prescribe Xromi® will be made solely by the physician independently of the study, as part of standard care. -

Treatment:

Drug: Xromi

Retrospective Comparator Cohort

Description:

Children with SCD and naïve to any hydroxycarbamide formulation at the index date. These participants will be identified retrospectively using the data from the last 10 years up to the date Xromi® was first used in children from 9 months to under 2 years of age at each individual site. The 24-month follow-up will be retrospective from the date they are matched to the exposed participant, irrespective of whether they start on any formulation of hydroxycarbamide during the follow-up.