Evaluation of Reporting of Antibody-Drug Conjugate Associated Sepsis-related Toxicities

Evaluation of Reporting of Antibody-Drug Conjugate Associated Sepsis-related Toxicities Using International Pharmacovigilance Database

Although antibody-drug conjugate(ADC) has proved effective in treating many cancers, few patients receiving ADC may experience rare but life-threatening sepsis-related toxicities such as sepsis and septic shock. Today, data about sepsis/septic shock are scarce.

The objective was to investigate reports of sepsis/septic shock adverse events related to ADC, including Gemtuzumab Ozogamicin, Trastuzumab Emtansine, Inotuzumab Ozogamicin, Enfortumab vedotin, Trastuzumab deruxtecan, Sacituzumab govitecan, Brentuximab Vedotin, Moxetumomab pasudotox, Polatuzumab Vedotin, Belantamab Mafodotin, loncastuximab tesirine and Tisotumab vedotin using international pharmacovigilance databases such as the FDA Adverse Event Reporting System (FAERS).

Study Overview

• Status: Completed
• Conditions: Agranulocytosis; Opportunistic Infections; Sepsis (SMQ)
• Intervention / Treatment: Drug: Antibody-Drug Conjugate; Drug: Antineoplastic and immunomodulating agents other than Antibody-Drug Conjugate

Detailed Description

Here, investigators use international pharmacovigilance databases such as the FDA Adverse Event Reporting System (FAERS) of individual safety case reports, to identify cases of sepsis-related toxicities related to ADC.

• Study Type: Observational
• Enrollment (Actual): 24618

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cancer patients treated with antibody-drug conjugate and experiencing sepsis-related toxicities.

Description

Inclusion Criteria:

Case reported in the FDA Adverse Event Reporting System (FAERS) or other international pharmacovigilance database of individual safety case reports to 12/31/2022 Adverse event reported were included the report with MedDRA terms: Sepsis(SMQ), agranulocytosis(SMQ), Opportunistic infections (SMQ).

Patients treated with ADC included: Gemtuzumab Ozogamicin, Trastuzumab Emtansine, Inotuzumab Ozogamicin, Enfortumab vedotin, Trastuzumab deruxtecan, Sacituzumab govitecan, Brentuximab Vedotin, Moxetumomab pasudotox, Polatuzumab Vedotin, Belantamab Mafodotin, loncastuximab tesirine and Tisotumab vedotin. Other cancer patients received common drug therapies such as chemotherapy, targeted therapy or immunotherapy would also be included as a comparator.

Exclusion Criteria:

Chronology not compatible between ADC and adverse event (sepsis-related toxicities)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Antibody-Drug Conjugate (ADC); Sepsis-related toxicities induced by antibody-drug conjugate(ADC). Case reported in the FDA Adverse Event Reporting System (FAERS) of Sepsis-related toxicities of patient treated by ADC, with a chronology compatible with the drug toxicity Intervention: Drug: ADC	Drug: Antibody-Drug Conjugate; Compared the case reporting of sepsis-related toxicities among ADC and other common cancer drug therapies. ADC:including Gemtuzumab Ozogamicin, Trastuzumab Emtansine, Inotuzumab Ozogamicin, Enfortumab vedotin, Trastuzumab deruxtecan, Sacituzumab govitecan, Brentuximab Vedotin, Moxetumomab pasudotox, Polatuzumab Vedotin, Belantamab Mafodotin, loncastuximab tesirine and Tisotumab vedotin.
Common cancer drug therapies other than ADC; Sepsis-related toxicities induced by Common cancer drug therapies other than ADC. Case reported in the FDA Adverse Event Reporting System (FAERS) of Sepsis-related toxicities of patient treated by Common cancer drug therapies other than ADC, with a chronology compatible with the drug toxicity Intervention: Drug: Chemotherapy, targeted therapy, immunotherapy and so on.	Drug: Antineoplastic and immunomodulating agents other than Antibody-Drug Conjugate; We would like to include other common cancer drug therapies such as chemotherapy, targeted therapy, immunotherapy and so on as a comparator group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sepsis-related toxicity of antibody-drug conjugate.	Identification and report of the sepsis-related toxicity of ADC. The research includes the report with MedDRA terms: Sepsis(SMQ), agranulocytosis(SMQ), Opportunistic infections (SMQ). Drugs investigated are ADC: Gemtuzumab Ozogamicin, Trastuzumab Emtansine, Inotuzumab Ozogamicin, Enfortumab vedotin, Trastuzumab deruxtecan, Sacituzumab govitecan, Brentuximab Vedotin, Moxetumomab pasudotox, Polatuzumab Vedotin, Belantamab Mafodotin, loncastuximab tesirine and Tisotumab vedotin.	Case reported in the FDA Adverse Event Reporting System (FAERS) and other international pharmacovigilance database of individual safety case reports to 12/31/2022

Secondary Outcome Measures

Outcome Measure	Time Frame
Causality assessment of reported cardiovascular events according to the WHO system	Case reported in the FDA Adverse Event Reporting System (FAERS) and other international pharmacovigilance database of individual safety case reports to 12/31/2022
Description of the type of sepsis-related toxicities depending on the category of ADC	Case reported in the FDA Adverse Event Reporting System (FAERS) and other international pharmacovigilance database of individual safety case reports to 12/31/2022
Description of the drug-drug interactions associated with sepsis-related adverse events	Case reported in the FDA Adverse Event Reporting System (FAERS) and other international pharmacovigilance database of individual safety case reports to 12/31/2022
Description of the population of patients having a sepsis-related adverse events	Case reported in the FDA Adverse Event Reporting System (FAERS) and other international pharmacovigilance database of individual safety case reports to 12/31/2022
Description of the pathologies (cancer) for which the incriminated drugs have been prescribed	Case reported in the FDA Adverse Event Reporting System (FAERS) and other international pharmacovigilance database of individual safety case reports to 12/31/2022

Collaborators and Investigators

• Sponsor: Central South University

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 22, 2022
• Primary Completion (ACTUAL): May 22, 2022
• Study Completion (ACTUAL): June 1, 2022

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (ACTUAL): April 27, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 19, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Parasitic Diseases; Leukopenia; Leukocyte Disorders; Sepsis; Toxemia; Opportunistic Infections; Agranulocytosis; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoconjugates; Antineoplastic Agents
• Other Study ID Numbers: CSU20220499

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No