EXploring Immune-related Adverse Events of Immune checkpoinT Inhibitors Using VigiBase, the WHO Pharmacovigilance Database

Cancer Clinical Trial

— EXIT  

Official title:

Immune-related Adverse Events From Immune Checkpoint Inhibitor Characterization Using VigiBase, the WHO Pharmacovigilance Database: An Exploration of Adverse Event Patterns and Signal Detection.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05934214
• Other study ID #: CIC1421-23-05
• Status: Completed
• Start date: January 1, 2023
• Est. completion date: February 29, 2024

Study information

• Verified date: July 2023
• Source: Groupe Hospitalier Pitie-Salpetriere
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an observational, retrospective pharmacovigilance study based on reports registered and transmitted in VigiBase®, the WHO's international database.

This study includes all reports identified as exposure to an ICI and suspect of inducing adverse drug reaction.

The aim of the study is to characterize immune-related adverse reactions associated with immune-checkpoint inhibitors, particularly their time-to-onset, co-occurence, factors associate with their over-report and fatality.

Description:

Over the past ten years, immuno-oncology (IO) has gradually integrated the therapeutic arsenal of cancer treatment. CTLA-4, program-death 1 (PD1) and its ligand (PD-L1) and LAG3 were found to be major targets active in multiple tumor types. Immune checkpoint inhibitors (ICI) are antibodies blocking these targets and became a cornestone of cancer treatment.

This is an observational, retrospective pharmacovigilance study based on reports registered and transmitted in VigiBase®, the WHO's international database. VigiBase is managed by the Uppsala Monitoring Centre (UMC, Uppsala, Sweden) and contains about 30 million reports (as of Jan 2023) submitted by national pharmacovigilance centers since 1967.

The use of VigiBase® for pharmacovigilance analyses is not dependent on institutional review board approval. It is conditioned on institutional access provided and approved by the Uppsala Monitoring Centre. Since spontaneous reporting systems are based on anonymity and the process only requires patient non-opposition, no informed consent was requested to use VigiBase® in this study.

This study includes all reports associated with an ICI. The query is performed using the Medical Dictionary for Regulatory Activities (MedDRA), between January 1st 2008 (year of first report of ICI in VigiBase), and January 1st 2023. The analysis focused on reports suspected to be induced by an ICI (as opposed to concurrent use).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141630
• Est. completion date: February 29, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Any report with an ICI "Suspect" or "Interacting" with the reported adverse drug reaction.

Exclusion Criteria:

• ICI not FDA approved

• No irAE identified in report

Related Conditions & MeSH terms

• Cancer
• Immune-related Adverse Event
• Myocarditis

Intervention

Drug:
• Immune checkpoint inhibitor
Reports associated with an an Immune checkpoint inhibitor with a status of "Suspect" or "Interacting" ICI will include the following list of FDA-apporved ICIs: nivolumab, pembrolizumab, cemiplimab, dostarlimab, durvalumab, atezolizumab, avelumab, ipilimumab, tremelimumab, relatlimab

Locations

Country	Name	City	State
France	AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.	Paris
France	CIC Paris-Est / Institut Curie	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Groupe Hospitalier Pitie-Salpetriere	Institut Curie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Factors associated with an increased rate of fatality among reports with an immune-related adverse event (irAE).	Reports with a fatal outcome will be compared to reports with no fatal outcome. Odds ratio will be calculated to compare covariates potentially associated with an increase risk of fatality, including irAE type, cancer type reported, patient's age, gender, comorbidities, type of ICI or ICI combination and other treatments.	any report prior to january 2023
Secondary	Factors associated with an increased reporting of main irAE types	Main irAEs are identified through MedDRA terms declared. For each irAE and each risk factors, an odds ratio will be calculated to assess a potential over-reporting. Factors evaluated will include but will not be limited to: cancer type, anticancer treatment type, socio-demographic variables (gender, age, country of reporting etc ...), year of reporting among others.	any report prior to january 2023
Secondary	Time to onset for each irAE type		any report prior to january 2023
Secondary	Rate of relapse with treatment rechallenge	For each irAE, the rate (percentage) of irAE reccurence after treatment rechallenge.	any report prior to january 2023