How has the COVID-19 pandemic affected clinical trial site restrictions, drug delivery, dosing, patient monitoring, and follow-up?
Coronavirus disease 2019 (COVID-19) has disrupted everyday life for people all over the globe, with more than 40.5 million cases to date. The effects of the pandemic are felt across every facet of human life, from our interpersonal relationships to our work lives to our finances.
But what happens with clinical studies in progress? How has the pandemic affected trial site restrictions, drug delivery, dosing, patient monitoring, and follow-up?
At the virtual ID Week 2020, investigators presented an analysis of the pandemic’s impact on dosing in 6 ongoing global phase 2b and 3b clinical trials of long-acting cabotegravir and rilpivirine (CAB+RPV LA), currently in development as an antiretroviral therapy (ART) for HIV infection. The treatment combination is made up of ViiV’s cabotegravir along with rilpivirine from Janssen Pharmaceutical Companies of Johnson & Johnson and administered via intramuscular injection monthly or every 2 months.
"People living with HIV may have events in their lives that could cause them to miss an injection appointment," Maggie Czarnogorski, MD, MPH, head of Innovation and Implementation Science at ViiV Healthcare and presenting author, told Contagion®. "While daily oral dosing can be used to cover missed injections, the COVID-19 pandemic presented us with a real-time test to implementing this novel regimen and an unexpected opportunity to analyze how injection interruptions were managed."
Czarnogorski's team aggregated data from the following ongoing CAB+RPV LA trials through September 15, 2020: LATTE-2, ATLAS, ATLAS-2M, FLAIR, POLAR, and CUSTOMIZE. Although data collection continues, investigators categorized and summarized initial information to show trends and to evaluate the impact of the pandemic on trial dosing.
According to data from 1744 study participants, a total of 129 (7%) had injection site visits that were impacted by COVID-19. Clinical closure or staffing constraints interrupted dosing for 54 (42%) participants; self-quarantine interrupted dosing for 11 (9%) participants; confirmed or suspected COVID-19 infection interrupted dosing for 11 (9%) participants; and 46 (36%) participants cited other reasons for dosing interruption.
Clinical trial participants in North America experienced the highest rate of impact (58%), followed by participants in Europe (26%), South Africa (13%), and Latin America (3%). Participants were majority male (79%) and mostly white (65%), with a median age of 35.
Investigators implemented a few mitigation strategies, including short-term oral therapy with CAB+RPV for 94 participants (73%), short-term standard-of-care ART for 27 participants (21%), and rescheduling of long-acting injections for 7 participants (5%).
There have been no reports of suspected or confirmed virologic failure for any participants impacted by COVID-19 to date, although viral load data collection is ongoing. A total of 121 (91%) impacted participants have restarted long-acting dosing.
"The results of this analysis showed that no antiretroviral therapy interruptions were found across the entirety of the ongoing clinical development program for long-acting cabotegravir and rilpivirine," Czarnogorski told Contagion®. "When missed visits occurred due to the pandemic, they were manageable and successfully mitigated, primarily by switching patients onto short periods of daily oral therapy of cabotegravir and rilpivirine, with no resulting virologic failure or emerging resistance."
The study, “Summary of COVID-Related Impact on Cabotegravir and Rilpivirine Long-Acting (CAB+RPV LA) Dosing Across the Six Ongoing Global Phase IIb and IIIb Clinical Trials,” was presented virtually at ID Week 2020.