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

Recruiting

• Conditions: Sickle Cell Disease
• Interventions: Drug: Xromi

• Registration Number: NCT06923111
• Lead Sponsor: Nova Laboratories Limited

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.

Study Timeline

• Study First Submitted: 2025-04-03
• Study First Submitted QC: 2025-04-03
• Study First Posted: 2025-04-11
• Status Verified: 2025-05
• Study Start: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16
• Primary Completion: 2029-02
• Study Completion: 2029-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Prospective Exposure Cohort	Xromi	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. -

Primary Outcome Measures

Name	Time	Method
AESI - Bacterial Infection	Pre-baseline, Baseline to 24 months	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.
AESI - Viral Infection	Pre-baseline, Baseline to 24 months	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 viral infection.
AESI - Fungal Infection	Pre-baseline, Baseline to 24 months	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 fungal infection.
AESI - Myelosuppression (Neutropenia)	Pre-baseline, Baseline to 24 months	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
AESI - Myelosuppression (Reticulocytopenia)	Pre-baseline, Baseline to 24 months	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 reticulocytopenia is ARC \<80 x 10\^9/L, unless Hb \>90 g/L,
AESI - Myelosuppression (Thrombocytopenia)	Pre-baseline, Baseline to 24 months	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 thrombocytopenia defined as platelets \<80 x 10\^9/L.
AESI - Myelosuppression (Anaemia)	Pre-baseline, Baseline to 24 months	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 anaemia defined as Hb \<45 g/L.
AESI - Abnormal Weight Gain	Baseline to 24 months	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
AESI - Abnormal Weight Loss	Baseline to 24 months	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
AESI - Increase in Hepatic Enzyme (ALT)	Baseline to 24 months	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)
AESI - Increase in Hepatic Enzyme (AST)	Baseline to 24 months	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 Aspartate transaminase (AST) increased (U/L)
AESI - Alopecia	Pre-baseline, Baseline to 24 months	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).
AESI - Other Hair Loss	Pre-baseline, Baseline to 24 months	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).
AESI - Skin Hyperpigmentation	Pre-baseline, Baseline to 24 months	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).
AESI - Rash	Pre-baseline, Baseline to 24 months	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 a rash (a skin and subcutaneous tissue disorder).
AESI - Skin Ulcers	Pre-baseline, Baseline to 24 months	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).
AESI - Growth Retardation	Pre-baseline, Baseline to 24 months	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).

Secondary Outcome Measures

Name	Time	Method
Other Adverse Events	Baseline to 24 months	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.
Painful Vaso-occlusive Crisis (VOC)	Pre-baseline, Baseline to 24 months	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.
Acute Chest Syndrome (ACS)	Pre-baseline, Baseline to 24 months	Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Splenomegaly	Pre-baseline, Baseline to 24 months	Occurrence of the clinical event Splenomegaly will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Priapism	Baseline to 24 months	Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Hepatobiliary disorder	Pre-baseline, Baseline to 24 months	Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Splenic Sequestration Crisis	Pre-baseline, Baseline to 24 months	Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Cerebrovascular accident	Pre-baseline, Baseline to 24 months	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
Abnormal or Conditional TCD	Pre-baseline, Baseline to 24 months	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)
Hospitalisations for SCD	Pre-baseline, Baseline to 24 months	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.
Other Clinical Events	Pre-baseline, Baseline to 24 months	Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Other Event - Death	Baseline to 24 months	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
Surgery	Pre-baseline, Baseline to 24 months	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.
Blood Transfusion	Pre-baseline, Baseline to 24 months	Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Non-hospitalised Visit for SCD	Pre-baseline, Baseline to 24 months	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
Haemoglobin (Hb)	Pre-baseline, Baseline to 24 months	(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.
Foetal Haemoglobin (HbF)	Pre-baseline, Baseline to 24 months	(%) 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.
Haemoglobin Fractions	Pre-baseline, Baseline to 24 months	(%) 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.; - Haemoglobinopathy screen results including: HbS, HbA, HbA2, HbC
Absolute Neutrophil Count (ANC)	Pre-baseline, Baseline to 24 months	(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.
Absolute Reticulocyte Count (ARC)	Pre-baseline, Baseline to 24 months	(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.
Platelet Count	Pre-baseline, Baseline to 24 months	(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.
White Blood Cell Count (WBC)	Pre-baseline, Baseline to 24 months	(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.
Mean Corpuscular Volume (MCV)	Pre-baseline, Baseline to 24 months	(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.
Mean Corpuscular Haemoglobin (MCH)	Pre-baseline, Baseline to 24 months	(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.
Ferritin	Pre-baseline, Baseline to 24 months	(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.
Transferrin Saturation	Pre-baseline, Baseline to 24 months	(%) 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.
Alanine Transaminase (ALT)	Pre-baseline, Baseline to 24 months	(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.
Alkaline Phosphatase (ALP)	Pre-baseline, Baseline to 24 months	(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.
Aspartate Transaminase (AST)	Pre-baseline, Baseline to 24 months	(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.
Total Bilirubin	Pre-baseline, Baseline to 24 months	(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.
Lactate Dehydrogenase	Pre-baseline, Baseline to 24 months	(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.
Gamma-Glutamyl Transferase (GGT)	Pre-baseline, Baseline to 24 months	(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.
Serum Creatinine	Pre-baseline, Baseline to 24 months	(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.
Estimated Glomular Filtration Rate (eGFR)	Pre-baseline, Baseline to 24 months	(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.
Albumin-Creatinine Ratio (ACR)	Pre-baseline, Baseline to 24 months	(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.
Liver Size	Pre-baseline, Baseline to 24 months	(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.
Spleen Size	Pre-baseline, Baseline to 24 months	(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.
Maximum Time Averaged Mean Velocity (TAMV)	Pre-baseline, Baseline to 24 months	(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.

Trial Locations

Locations (5)

Basildon University Hospital; 🇬🇧 Basildon, Essex, United Kingdom

Noah's Ark Children's Hospital for Wales; 🇬🇧 Cardiff, Leicestershire, United Kingdom

University College London Hospital; 🇬🇧 London, North London, United Kingdom

The Royal London Hospital; 🇬🇧 London, Whitechapel, United Kingdom

Kings College Hospital; 🇬🇧 London, United Kingdom