PRJ2203: Dolutegravir Post Authorization Safety Study (PASS)

Infection, Human Immunodeficiency Virus I Clinical Trial

Official title:

A Prospective Observational Cohort Study to Monitor and Compare the Occurrence of Hypersensitivity Reaction and Hepatotoxicity in Patients Receiving Dolutegravir (With and Without Abacavir) or Other Integrase Inhibitors (With or Without Abacavir)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03327740
• Other study ID #: 201177
• Secondary ID: PRJ2203
• Status: Completed
• Start date: September 30, 2014
• Est. completion date: December 31, 2019

Study information

• Verified date: February 2020
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Dolutegravir (DTG) is recommended for both treatment-naïve and treatment-experienced, HIV infected adults and paediatric subjects aged 12 years and older and weighing at least 40 kg. One case of suspected DTG hypersensitivity (HSR) reaction from among over 1500 subjects exposed to the drug at the time of submission in 4Q2012, has been identified; this subject experienced a diffuse maculopapular rash with fever and elevated liver enzymes. Isolated rash was uncommon in the DTG programme with less than 1% of clinical trial subjects experiencing treatment related rash. The pharmacovigilance strategy for DTG and DTG-containing products is to implement a post-marketing risk management program to further quantify the risk of HSR and compare it to that of other integrase inhibitors, and to possibly determine associated risk factors. In addition, the post-authorization safety study will monitor and compare hepatotoxicity and severe skin rash following initiation of DTG or other integrase inhibitor (raltegravir (RAL) or elvitegravir (EGV) based antiretroviral regimens (ARV). Further to be able to distinguish the above symptoms and reactions caused by DTG or the other integrase inhibitor regimen from that of abacavir (ABC), known to cause hypersensitivity reaction, the integrase inhibitor groups will be compared in combinations with and without ABC. This five year-long safety study will be conducted through collaboration with EuroSIDA, a well established prospective observational cohort study of more than 18,200 subjects followed in 107 hospitals in 31 European countries, plus Israel and Argentina. This is a five year-long non-interventional prospective cohort study nested within the EuroSIDA study. The study population will include HIV positive subjects over the age of 16 years from EuroSIDA clinical sites, who are new users of DTG or other integrase inhibitors with and without ABC. Following initiation of DTG with ABC based antiretroviral regimen or DTG without ABC or regimens containing other integrase inhibitors (RAL, EGV) with or without ABC or any other DTG based ARV regimen as monotherapy or two-drug regimens, the study will aim to a) Monitor and compare hypersensitivity reaction, b) Monitor and compare hepatotoxicity, and c) Monitor and compare severe skin rash among all subjects discontinuing DTG or other integrase inhibitor regimens for any reason.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years and older

Eligibility

Inclusion Criteria:

• New users of DTG or users of other integrase inhibitor regimens (RAL and EGV)

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infection, Human Immunodeficiency Virus I

Intervention

Drug:
• DTG based ARV regimen with ABC
ARV regimens containing DTG and ABC
• DTG based ARV regimen without ABC
DTG based ARV regimens that do not contain ABC
• RAL or EGV based ARV regimens with ABC
RAL or EGV based regimens containing ABC
• RAL or EGV based regimens without ABC
RAL or EGV based ARV regimens that do not contain ABC
• Any other DTG based ARV regimen as monotherapy
Any other DTG based ARV regimens including DTG as monotherapy or two-drug regimens.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
ViiV Healthcare	GlaxoSmithKline

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with occurrence of hypersensitivity reactions (HSR), of any grade	Hypersensitivity reactions including fever, rash, gastrointestinal symptoms, constitutional symptoms, respiratory symptoms and eosinophilia will be summarized.	Up to 5 years
Primary	Number of subjects with hepatic dysfunction	Hepatic dysfunction will be indicated by liver chemistry tests	Up to 5 years