Efficacy and Safety of Selumetinib in Adults with NF1 who have Symptomatic, Inoperable Plexiform Neurofibromas.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

8 Dec 2021 → ongoing

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-507336-20-00

EudraCT number

2020-005607-39

ClinicalTrials.gov

NCT04924608

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the effect of selumetinib relative to placebo by assessment of confirmed partial and complete response rate (ORR) using volumetric MRI analysis as determined by ICR (per REiNS criteria) in participants with NF1 who have symptomatic, inoperable PN.

Secondary objectives 1

1. '- To compare the effect of selumetinib relative to placebo by assessment of chronic target PN pain intensity - To compare the effect of selumetinib relative to placebo by assessment of change in HRQoL from baseline in participants with NF1 who have symptomatic, inoperable PN - To demonstrate the effectiveness of selumetinib by assessment of confirmed partial and complete response rate (ORR) using volumetric MRI analysis as determined by ICR (per REiNS criteria) in participants with NF1 who have symptomatic, inoperable PN. - To assess the safety and tolerability of selumetinib alone and as compared to placebo - To assess the PK of selumetinib'

Conditions and MedDRA coding

Neurofibromatosis Type 1 (NF1) with Symptomatic, Inoperable Plexiform Neurofibromas (PN).

Study design 3 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001585-PIP01-13

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. '- Adults ≥ 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN - At least one target PN measurable by volumetric MRI analysis - Chronic target PN pain score documented for minimum period during screening period - Stable chronic PN pain medication use at enrollment - Adequate organ and marrow function'

Exclusion criteria 1

1. '- Confirmed or suspected malignant glioma or MPNST (low grade glioma, including optic glioma not requiring systemic therapy or radiation therapy are exempt from this exclusion) - History of malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence - Clinically significant cardiovascular disease, including inherited coronary disease, acute coronary syndrome within 6 months prior to enrollment, uncontrolled angina, symptomatic heart failure, cardiomyopathy, severe valvular heart disease, abnormal LVEF and uncontrolled hypertension - Ophthalmological findings/conditions including intraocular pressure > 21 mmHg, RPED/CSR or RVO - Prior exposure to MEK inhibitors'

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) using volumetric MRI analysis as determined by ICR per REiNS criteria.

Secondary endpoints 1

1. Change from baseline in chronic target PN pain intensity. Change from baseline in PlexiQoL total score. Objective Response Rate. Duration of Response. Progression Free Survival. Time to progression. Time to Response. Best percentage change from baseline in target PN vol. Pain palliation, pain medication use, pain interference, physical functioning, health related quality of life PROs&health status. Safety&tolerability. Plasma concentrations&PK parameters of selumetinib&Ndesmethyl selumetinib.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

5 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications