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

Nova Laboratories Limited180 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

180

Conditions

Sickle Cell Disease

Interventions

XromiDRUG

Xromi is indicated for the prevention of vaso-occlusive complications of Sickle Cell Disease in patients over 9 months of age as part of standard clinical practice

Eligibility

Sex: ALLMin age: 9 MonthsMax age: 23 Months

Medical Language ↔ Plain English

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.

Locations (5)

Basildon University Hospital

Basildon, Essex, United Kingdom

NOT_YET_RECRUITING

Noah's Ark Children's Hospital for Wales

Cardiff, Leicestershire, United Kingdom

NOT_YET_RECRUITING

University College London Hospital

London, North London, United Kingdom

RECRUITING

The Royal London Hospital

London, Whitechapel, United Kingdom

NOT_YET_RECRUITING

Kings College Hospital

London, United Kingdom

RECRUITING

Outcomes

Primary Outcomes

AESI - Myelosuppression (Neutropenia)

Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Myelosuppression protocol definition of neutropenia is ANC \<1.0 x 10\^9/L

Time frame: Pre-baseline, Baseline to 24 months

AESI - Myelosuppression (Reticulocytopenia)

Time frame: Pre-baseline, Baseline to 24 months

AESI - Myelosuppression (Thrombocytopenia)

Time frame: Pre-baseline, Baseline to 24 months

AESI - Myelosuppression (Anaemia)

Time frame: Pre-baseline, Baseline to 24 months

AESI - Abnormal Weight Gain

Weight (kg) Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort and standard care guidelines

Time frame: Baseline to 24 months

AESI - Abnormal Weight Loss

Time frame: Baseline to 24 months

AESI - Increase in Hepatic Enzyme (ALT)

Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort and normal laboratory ranges. Defined as an increase in hepatic enzyme Alanine transaminase (ALT) increased (U/L)

Time frame: Baseline to 24 months

AESI - Increase in Hepatic Enzyme (AST)

Time frame: Baseline to 24 months

AESI - Alopecia

Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of alopecia (a skin and subcutaneous tissue disorder).

Time frame: Pre-baseline, Baseline to 24 months

AESI - Other Hair Loss

Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of other hair loss (a skin and subcutaneous tissue disorder).

Time frame: Pre-baseline, Baseline to 24 months

AESI - Skin Hyperpigmentation

Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of skin hyperpigmentation, including oral and nail hyperpigmentation.(a skin and subcutaneous tissue disorder).

Time frame: Pre-baseline, Baseline to 24 months

AESI - Rash

Time frame: Pre-baseline, Baseline to 24 months

AESI - Skin Ulcers

Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of skin ulcer, including leg ulcer (a skin and subcutaneous tissue disorder).

Time frame: Pre-baseline, Baseline to 24 months

AESI - Growth Retardation

height/length (cm) Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort and standard care guidelines (as a drop of 2 or more centiles on growth charts over time).

Time frame: Pre-baseline, Baseline to 24 months

AESI - Bacterial Infection

Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in the protocol as a proven or treated bacterial infection.

Time frame: Pre-baseline, Baseline to 24 months

AESI - Viral Infection

Time frame: Pre-baseline, Baseline to 24 months

AESI - Fungal Infection

Time frame: Pre-baseline, Baseline to 24 months

Secondary Outcomes

Other Adverse Events

Occurrence of other adverse events (AE), adverse reactions (AR) and serious adverse events (SAE) or serious adverse reactions (SAR) will be collected during follow-up.

Time frame: Baseline to 24 months

Painful Vaso-occlusive Crisis (VOC)

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®. \- VOC events will include dactylitis.

Time frame: Pre-baseline, Baseline to 24 months

Acute Chest Syndrome (ACS)

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

Time frame: Pre-baseline, Baseline to 24 months

Splenomegaly

Occurrence of the clinical event Splenomegaly will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

Time frame: Pre-baseline, Baseline to 24 months

Priapism

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

Time frame: Baseline to 24 months

Hepatobiliary disorder

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

Time frame: Pre-baseline, Baseline to 24 months

Splenic Sequestration Crisis

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

Time frame: Pre-baseline, Baseline to 24 months

Central Contacts

Hussain Mulla, PhD

CONTACT

+44 (0)116 223 0100 hussain.mulla@novalabs.co.uk

Sarah Edwards, PhD

CONTACT

+44 (0)116 223 0100 sarah.edwards@novalabs.co.uk

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®. Defined in the protocol as any surgery that is planned, emergency, or due to pre-existing conditions e.g. SCD.

Time frame: Pre-baseline, Baseline to 24 months

Blood Transfusion

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

Time frame: Pre-baseline, Baseline to 24 months

Cerebrovascular accident

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®. The protocol definition includes silent stroke

Time frame: Pre-baseline, Baseline to 24 months

Abnormal or Conditional TCD

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®. \- Transcranial Doppler Scan (TCD)

Time frame: Pre-baseline, Baseline to 24 months

Hospitalisations for SCD

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®. The reason for hospitalisation and duration will be collected.

Time frame: Pre-baseline, Baseline to 24 months

Non-hospitalised Visit for SCD

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®. Protocol definition includes Emergency department (ED) visits/treatment centres/paediatric ward/day unit attendances for SCD

Time frame: Pre-baseline, Baseline to 24 months

Other Clinical Events

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

Time frame: Pre-baseline, Baseline to 24 months

Other Event - Death

Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator. Protocol definition includes any death occurring in the study both related and un-related to Xromi treatment

Time frame: Baseline to 24 months

Haemoglobin (Hb)

(g/L) or (g/dl) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Foetal Haemoglobin (HbF)

(%) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Haemoglobin Fractions

Time frame: Pre-baseline, Baseline to 24 months

Absolute Neutrophil Count (ANC)

(10\^9/L or /nL) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Absolute Reticulocyte Count (ARC)

Time frame: Pre-baseline, Baseline to 24 months

Platelet Count

Time frame: Pre-baseline, Baseline to 24 months

White Blood Cell Count (WBC)

Time frame: Pre-baseline, Baseline to 24 months

Mean Corpuscular Volume (MCV)

(fl) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Mean Corpuscular Haemoglobin (MCH)

(pg) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Ferritin

(µg/L) Iron Profile. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Transferrin Saturation

(%) Iron Profile. Iron binding saturation or transferrin saturation. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Alanine Transaminase (ALT)

(U/L) Liver Function tests. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Alkaline Phosphatase (ALP)

Time frame: Pre-baseline, Baseline to 24 months

Aspartate Transaminase (AST)

Time frame: Pre-baseline, Baseline to 24 months

Total Bilirubin

(µmol/L or mg/dl) Liver Function tests. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Lactate Dehydrogenase

Time frame: Pre-baseline, Baseline to 24 months

Gamma-Glutamyl Transferase (GGT)

Time frame: Pre-baseline, Baseline to 24 months

Serum Creatinine

(µmol/L or mg/dl) Renal function test. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Estimated Glomular Filtration Rate (eGFR)

(ml/min/1.73m\^2) Renal function test. Calculated value, Interpreted in line with UK CKD guidelines from creatinine values. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Albumin-Creatinine Ratio (ACR)

(Calculated value). Renal function test. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Liver Size

(cm) from costal margin. Physiological Assessment. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months

Spleen Size

Time frame: Pre-baseline, Baseline to 24 months

Maximum Time Averaged Mean Velocity (TAMV)

(cm/s) Cardiovascular function, assessed using transcranial doppler scan velocities. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Time frame: Pre-baseline, Baseline to 24 months