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

NCT ID: NCT06923111

Last Updated: 2025-08-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

180 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-06-09

Study Completion Date

2029-06-30

Brief Summary

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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

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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.

Conditions

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Sickle Cell Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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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.

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Xromi

Intervention Type 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

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.

No interventions assigned to this group

Interventions

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Xromi

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

Intervention Type DRUG

Other Intervention Names

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hydroxycarbamide oral solution 100mg/ml liquid hydroxyurea LO1XX05

Eligibility Criteria

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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.

* 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

* 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


* 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.
Minimum Eligible Age

9 Months

Maximum Eligible Age

23 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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OXON Epidemiology

INDUSTRY

Sponsor Role collaborator

Nova Laboratories Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hussain Dr Mulla, PhD

Role: STUDY_DIRECTOR

Nova Laboratories Ltd.

Sara Dr Trompeter, MD

Role: PRINCIPAL_INVESTIGATOR

University College London Hospitals

Locations

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Basildon University Hospital

Basildon, Essex, United Kingdom

Site Status NOT_YET_RECRUITING

Noah's Ark Children's Hospital for Wales

Cardiff, Leicestershire, United Kingdom

Site Status NOT_YET_RECRUITING

University College London Hospital

London, North London, United Kingdom

Site Status RECRUITING

The Royal London Hospital

London, Whitechapel, United Kingdom

Site Status NOT_YET_RECRUITING

Kings College Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Hussain Mulla, PhD

Role: CONTACT

+44 (0)116 223 0100

Sarah Edwards, PhD

Role: CONTACT

+44 (0)116 223 0100

Facility Contacts

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Sarah Edwards, PhD

Role: primary

+44 (0) 116 223 0100

Sarah Edwards, PhD

Role: primary

+44 (0) 116 223 0100

Sarah Edwards, PhD

Role: primary

+44 (0) 116 223 0100

Sarah Edwards, PhD

Role: primary

+44 (0) 116 223 0100

Sarah Edwards, PhD

Role: primary

+44 (0) 116 223 0100

References

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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.

Reference Type BACKGROUND
PMID: 37171600 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19731330 (View on PubMed)

Other Identifiers

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EUPAS1000000076

Identifier Type: OTHER

Identifier Source: secondary_id

CHIL 62837

Identifier Type: OTHER

Identifier Source: secondary_id

334976

Identifier Type: OTHER

Identifier Source: secondary_id

NOVDD-001

Identifier Type: -

Identifier Source: org_study_id

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