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

NCT06923111 | Recruiting FDA Drug

• 4 other identifiers: NOVDD-001EUPAS1000000076CHIL 62837334976
• Study Type: observational
• Target: 180
• Locations: 2 countries
• Sites: 12

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.

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

Outcome Measures

Primary Outcomes (17)

• 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

  Pre-baseline, Baseline to 24 months

• AESI - Myelosuppression (Reticulocytopenia)

  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,

  Pre-baseline, Baseline to 24 months

• AESI - Myelosuppression (Thrombocytopenia)

  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.

  Pre-baseline, Baseline to 24 months

• AESI - Myelosuppression (Anaemia)

  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.

  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

  Baseline to 24 months

• AESI - Abnormal Weight Loss

  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

  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)

  Baseline to 24 months

• AESI - Increase in Hepatic Enzyme (AST)

  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)

  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).

  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).

  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).

  Pre-baseline, Baseline to 24 months

• AESI - Rash

  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).

  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).

  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).

  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.

  Pre-baseline, Baseline to 24 months

• AESI - Viral 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 viral infection.

  Pre-baseline, Baseline to 24 months

• AESI - Fungal 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 fungal infection.

  Pre-baseline, Baseline to 24 months

Secondary Outcomes (38)

• Other Adverse Events

  Baseline to 24 months

• Painful Vaso-occlusive Crisis (VOC)

  Pre-baseline, Baseline to 24 months

• Acute Chest Syndrome (ACS)

  Pre-baseline, Baseline to 24 months

• Splenomegaly

  Pre-baseline, Baseline to 24 months

• Priapism

  Baseline to 24 months

Study Arms (2)

Prospective Exposure Cohort

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. \-

Drug: Xromi

Retrospective Comparator Cohort

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.

Interventions

Xromi DRUG

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

Also known as: hydroxycarbamide oral solution 100mg/ml, liquid hydroxyurea, LO1XX05

Prospective Exposure Cohort

Eligibility Criteria

• Age: 9 Months - 23 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.
• Use of hydroxycarbamide of any formulation before or at the index date.

Sponsors & Collaborators

• Nova Laboratories Limited: lead
• OXON Epidemiology: collaborator

Study Sites (12)

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, Germany

RECRUITING

Basildon University Hospital

Basildon, United Kingdom

RECRUITING

Noah's Ark Children's Hospital for Wales

Cardiff, United Kingdom

RECRUITING

Evelina London Children's Hospital

London, United Kingdom

RECRUITING

Kings College Hospital

London, United Kingdom

RECRUITING

North Middlesex University Hospital

London, United Kingdom

RECRUITING

The Royal London Hospital

London, United Kingdom

RECRUITING

University College London Hospital

London, United Kingdom

RECRUITING

Whittington Hospital

London, United Kingdom

RECRUITING

Royal Manchester Children's Hospital

Manchester, United Kingdom

RECRUITING

John Radcliffe Hospital

Oxford, United Kingdom

RECRUITING

Related Publications (2)

• 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.

  PMID: 37171600 BACKGROUND

• 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.

  PMID: 19731330 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Hemoglobinopathies

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Hussain Dr Mulla, PhD

  Nova Laboratories Ltd.

  STUDY DIRECTOR

• Sara Dr Trompeter, MD

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Central Study 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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 11, 2025
• Study Start: June 9, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: March 2025 - upto 25 years from end of study.
• Access Criteria: Publicly accessible study protocol via the HMA-EMA RWD Catalogues and the study protocol has been shared publicly (EUPAS1000000076) Publicly accessible aggregated study results via ClinicalTrials.Gov.

Locations

GB (10); DE (2)