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

March 4, 2024 updated by: Joe Elie Salem, Groupe Hospitalier Pitie-Salpetriere

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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).

Study Type

Observational

Enrollment (Actual)

141630

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.
      • Paris, France, 75013
        • CIC Paris-Est / Institut Curie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Any reports with an immune-related drug reaction attributed to an immune checkpoint inhibitor

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
immune-related adverse event reaction
Reports of identified immune-related adverse event reaction
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Factors associated with an increased rate of fatality among reports with an immune-related adverse event (irAE).
Time Frame: any report prior to january 2023
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Factors associated with an increased reporting of main irAE types
Time Frame: any report prior to january 2023
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
Time to onset for each irAE type
Time Frame: any report prior to january 2023
any report prior to january 2023
Rate of relapse with treatment rechallenge
Time Frame: any report prior to january 2023
For each irAE, the rate (percentage) of irAE reccurence after treatment rechallenge.
any report prior to january 2023

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Groupe Hospitalier Pitie-Salpetriere

Collaborators

Institut Curie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2023

Primary Completion (Actual)

December 31, 2023

Study Completion (Actual)

February 29, 2024

Study Registration Dates

First Submitted

June 16, 2023

First Submitted That Met QC Criteria

July 5, 2023

First Posted (Actual)

July 6, 2023

Study Record Updates

Last Update Posted (Estimated)

March 5, 2024

Last Update Submitted That Met QC Criteria

March 4, 2024

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIC1421-23-05

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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