An observational study in Neurofibromatosis Type 1, sponsored by AstraZeneca. Active, not recruiting at 46 sites in 10 countries. Open to participants aged 3 Years to 17 Years. Per ClinicalTrials.gov, last updated 2026-08-24.
Sponsored by AstraZeneca · Observational
Neurofibromatosis type 1 (NF1) is a rare, autosomal dominant genetic disorder that is caused by germline mutations in the NF1 tumour suppressor gene, which encodes the tumour suppressor protein neurofibromin 1. Plexiform neurofibromas (PN) are histologically benign nerve sheath tumours, which typically grow along large nerves and plexi.
On 5 March 2020, a centralised Marketing Authorisation Application was submitted to the European Medicines Agency (EMA), Marketing Authorisation in EU was granted on 17 Jun 2021.
As part of the approval process, a Risk Management Plan (RMP) was developed and submitted to the EMA to summarise the safety concerns emerging from the clinical development program. The RMP included additional pharmacovigilance plans for a noninterventional Post-authorisation Safety Study (PASS) to further characterise the safety of selumetinib in paediatric patients with NF1-related PN in routine clinical practice.
The planned non-interventional PASS will address gaps in knowledge identified by the RMP, including the important identified risk and some of the potential risks and missing information on long-term developmental toxicity in children, by characterising the safety profile associated with selumetinib use among paediatric patients (age d 8 to \< 18 years old) with a diagnosis of NF1 with symptomatic, inoperable PN.
This study is a specific obligation in the context of a conditional marketing authorisation for selumetinib (ie, Category 2 PASS). Study results will contribute to updating the safety profile of selumetinib in a relatively large population of patients with different personal characteristics across multiple health care systems and patterns of real-world clinical practice in European countries and Israel.
The study will enrol 2 cohorts:
Neurofibromatosis type 1 (NF1) is a rare, autosomal dominant genetic disorder that is caused by germline mutations in the NF1 tumour suppressor gene, which encodes the tumour suppressor protein neurofibromin 1. Plexiform neurofibromas (PN) are histologically benign nerve sheath tumours, which typically grow along large nerves and plexi.
On 5 March 2020, a centralized Marketing Authorisation Application was submitted to the European Medicines Agency (EMA), Marketing Authorization in EU was granted on 17 Jun 2021.
As part of the approval process, a Risk Management Plan (RMP) was developed and submitted to the EMA to summarise the safety concerns emerging from the clinical development program. The RMP included additional pharmacovigilance plans for a non-interventional Post-authorisation Safety Study (PASS) to further characterise the safety of selumetinib in paediatric patients with NF1-related PN in routine clinical practice.
The RMP version 1.0 (succession 4) approved by EMA on 22 April 2021 had 1 important identified risk with selumetinib treatment:
-LVEF reduction
The RMP also identified 5 important potential risks with selumetinib treatment:
The planned non-interventional PASS will address gaps in knowledge identified by the RMP, including the important identified risk and some of the potential risks and missing information on long-term developmental toxicity in children, by characterising the safety profile associated with selumetinib use among paediatric patients (aged d 8 to \< 18 years old) with a diagnosis of NF1 with symptomatic, inoperable PN.
This study is a specific obligation in the context of a conditional marketing authorisation for selumetinib (ie, Category 2 PASS). Study results will contribute to updating the safety profile of selumetinib in a relatively large population of patients with different personal characteristics across multiple health care systems and patterns of real-world clinical practice in up to 52 specialist clinics for the treatment of pediatric patients with NF1 across up to 12 European countries and in Israel.
The primary objective of this study is:
- To characterise the safety of selumetinib, including up to 6 years of long-term safety, in paediatric patients with NF1-related symptomatic, inoperable PN, 8 to \< 18 years old who have not reached Tanner Stage V at the start of selumetinib treatment (Nested Prospective Cohort).
The secondary objective of this study is:
- To describe the demographic and clinical profile of the paediatric population 3 to \< 18 years old with NF1-related symptomatic inoperable PN who start selumetinib in routine clinical practice (Base Cohort).
The study observation period was anticipated to begin in Q2 of 2022, with some variation by country (actual start date was 23 May 2022). Patients will be enrolled after selumetinib access is commercially available and patients are able to receive the medicine as part of local clinical practice.
The target population for this study are patients with NF1 in the EU with symptomatic, inoperable PN who have been prescribed at least 1 dose of selumetinib and who are aged 3 to \< 18 years at the start of selumetinib treatment, except for those patients receiving treatment with a mitogen-activated protein kinase inhibitor before the index date.
The study will enrol 2 cohorts:
Patient screening will be conducted throughout the enrolment period and baseline data for all patients will be abstracted from medical records. Those meeting the criteria for enrolment in the Nested Prospective Cohort will be followed up during their routine standard of care visits with the treating clinician (expected to occur every 6 to 12 months) for up to 6 years.
216 studies on the registry are indexed under Neurofibromatosis 1; 41 are open to participants now.
This study's enrollment of 124 is above the median of 112 across 67 observational studies indexed under Neurofibromatosis 1.
Browse Neurofibromatosis 1 studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
The target population for this study are patients with NF1 with symptomatic, inoperable PN who have been prescribed at least 1 dose of selumetinib and who are aged 3 to \< 18 years at the start of selumetinib treatment, except for those patients receiving treatment with a mitogen-activated protein kinase inhibitor before the index date.
Exclusion Criteria:
The Base Cohort includes all enrolled patients aged 3 to \< 18 years.
The Nested Prospective Cohort will include the subset of Base Cohort patients aged 8 to \< 18 years who have not reached Tanner Stage V on the index date
LVEF reduction
LVEF reduction will be detected as present or absent and when present if symptomatic or asymptomatic. All cardiac tests conducted will be collected Measured on routine echocardiogram or a cardiac MRI (CT, angiography, etc.) and then collected into the study from the medical records.
Time frame: at routine clinical care throughout the follow up, with frequency of 6 to 12 months
Occurrence of Physeal dysplasia after treatment start
Physeal dysplasia will be detected as present or absent based on the physician reading of: MRI: Knee (preferred) or wrist X-ray: Knee (preferred) and/or wrist to assess growth plate Height and weight records
Time frame: at routine clinical care throughout the follow up, with frequency of 6 to 12 months
Rise of serum creatine phosphokinase levels AND concurrent musculoskeletal symptoms
A clinically meaningful rise in serum creatine phosphokinase (eg, above the normal limit or increase by 1 or more CTCAE grade shift) combined with musculoskeletal symptoms will be detected as present or absent based on the physician's reading, as a marker of potential myopathy
Time frame: at routine clinical care throughout the follow up, with frequency of 6 to 12 months, up to 6 years
Rise in transaminase (ALT and AST) and concurrent rise in bilirubin
A clinically meaningful rise in the measured levels (eg, above the normal limit or increase by 1 or more CTCAE grade shift) will be detected as present or absent, and when present if symptomatic or asymptomatic, as a marker of potential hepatotoxicity
Time frame: at routine clinical care throughout the follow up, with frequency of 6 to 12 months, up to 6 years
Cumulative incidence of ocular toxicity
An abnormal ocular examination will be detected as present or absent based on the physician's reading, as a marker of potential ocular toxicity
Time frame: at routine clinical care throughout the follow up, with frequency of 6 to 12 months
Cumulative incidence of Abnormal pubertal development
Tanner stage criteria (Stages I-V). Abnormal pubertal development will require interpretation by the Investigator with respect to Tanner Stage in the context of the patient's age; recorded as normal or abnormal (if abnormal, further specified as delayed puberty or precocious puberty)
Time frame: at routine clinical care throughout the follow up, with frequency of 6 to 12 months
baseline data - demographics
Demographics: Age
Time frame: At baseline - most recent assessments made within 365 days before the index date
baseline data - demographics
sex
Time frame: At baseline - most recent assessments made within 365 days before the index date
baseline data - demographics
height (cm)
Time frame: At baseline - most recent assessments made within 365 days before the index date
baseline data - demographics
weight (kg)
Time frame: At baseline - most recent assessments made within 365 days before the index date
baseline data - demographics
Tanner staging level
Time frame: At baseline - most recent assessments made within 365 days before the index date
baseline data - demographics
Ethnicity (where allowed by GDPR/privacy laws)
Time frame: At baseline - most recent assessments made within 365 days before the index date
Baseline data - Clinical characteristics
PN(s) (number, location, classification and morbidities)
Time frame: At baseline - most recent assessments made within 365 days before the index date
Baseline data - Clinical characteristics
prior medication and relevant procedures, concomitant medications
Time frame: At baseline - most recent assessments made within 365 days before the index date
Baseline data - Clinical characteristics
date of initial NF1 and PN diagnosis, NF1 origin (familial or spontaneous), and any genetic testing results
Time frame: At baseline - most recent assessments made within 365 days before the index date
Other Variables and Covariates
Height (cm)
Time frame: at baseline and throughout follow-up, up to 6 years
Other Variables and Covariates
Weight (kg)
Time frame: at baseline and throughout follow-up, up to 6 years
Other Variables and Covariates
Body surface area
Time frame: at baseline and throughout follow-up, up to 6 years
Other Variables and Covariates
Tanner staging (level from I to V)
Time frame: at baseline and throughout follow-up, up to 6 years
Other Variables and Covariates
Concomitant medications, including any medications used to treat AEs
Time frame: at baseline and throughout follow-up, up to 6 years
Other Variables and Covariates
Comorbidities
Time frame: at baseline and throughout follow-up, up to 6 years
Other Variables and Covariates
NF1-related clinical manifestation and complications
Time frame: at baseline and throughout follow-up, up to 6 years
Other Variables and Covariates
PN-related variables (including for any clinically important target PNs)
Time frame: at baseline and throughout follow-up, up to 6 years
Other Variables and Covariates
PN-related symptoms/morbidities
Time frame: at baseline and throughout follow-up, up to 6 years
Plan to share: Yes — The study protocol, study progress reports, and final study report will be included in regulatory communications in line with the RMP, PSUR, and other regulatory reporting requirements. Study reports will be prepared using a template following the GVP Module VIII Section B.6.3.
Supporting information: Study protocol, Csr
This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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