Clinical Data

Scientific Evidence Supporting this EUA

ACTT-2 (Adaptive COVID-19 Treatment Trial 2) Study in Hospitalized Adults Diagnosed with COVID-19 Infection

The ACTT-2 study was a randomized, double-blind, placebo-controlled clinical trial of hospitalized adults with confirmed SARS-CoV-2 infection that compared treatment with baricitinib and remdesivir (combination group; n=515) to treatment with placebo and remdesivir (placebo group; n=518). Patients had to have laboratory-confirmed SARS-CoV-2 infection, as well as at least one of the following to be enrolled in the trial: radiographic infiltrates by imaging, SpO₂ ≤94% on room air, a requirement for supplemental oxygen, or a requirement for mechanical ventilation.

Patients treated with the combination received the following regimen:

• Baricitinib 4 mg once daily (orally) for 14 days or until hospital discharge
• Remdesivir 200 mg on Day 1 and 100 mg once daily (via intravenous infusion) on subsequent days for a total treatment duration of 10 days or until hospital discharge

The primary endpoint, for the intent to treat population, was time to recovery within 29 days after randomization. Recovery was defined as:

• Being discharged from the hospital without limitations on activities,
• Being discharged from the hospital with limitations on activities and/or requiring home oxygen, or
• Hospitalized but not requiring supplemental oxygen and no longer requiring medical care.

The key secondary endpoint was clinical status on Day 15, as assessed on an 8-point ordinal scale (OS).

ACTT-2 Ordinal Scale

Patient Characteristics for ACTT-2

At randomization, mean age was 55 years (with 30% of patients aged 65 or older); 63% of patients were male, 51% were Hispanic or Latino; 48% were White, 15% were Black or African American, and 10% were Asian. At the time of randomization, 14% did not require supplemental oxygen, 55% required supplemental oxygen, 21% required noninvasive ventilation or high-flow oxygen, and 11% required invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). The most common comorbidities were obesity (56%), hypertension (52%), and type 2 diabetes (37%). Demographics and disease characteristics were balanced across the combination group and the placebo group.

ACTT-2 Primary and Key Secondary Efficacy Analyses^a

For the overall population, the median time to recovery (defined as discharged from hospital or hospitalized but not requiring supplemental oxygen or ongoing medical care) was 7 days for baricitinib and remdesivir compared to 8 days for placebo and remdesivir [hazard ratio: 1.15 (95% CI 1.00, 1.31); p=0.047]. Patients assigned to baricitinib and remdesivir were more likely to have a better clinical status (according to an 8-point ordinal scale) at Day 15 compared to patients assigned to placebo and remdesivir [odds ratio: 1.26 (95% CI 1.01, 1.57); p=0.044].

The proportion of patients who died or progressed to noninvasive ventilation/high-flow oxygen or invasive mechanical ventilation by Day 29 was lower in baricitinib and remdesivir (23%) compared to placebo and remdesivir (28%) [odds ratio: 0.74 (95% CI 0.56, 0.99); p=0.039]. Patients who required noninvasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO) at baseline needed to worsen by at least 1 point on an 8-point ordinal scale to progress.

The proportion of patients who died by Day 29 was 4.7% (24/515) for baricitinib and remdesivir vs. 7.1% (37/518) for placebo and remdesivir [Kaplan Meier estimated difference in Day 29 probability of mortality: -2.6% (95% CI -5.8%, 0.5%)].

Data on deaths, serious adverse events (SAEs), AEs leading to discontinuation, infections, and VTEs are summarized below.

Comparisons and Confidence Intervals for Adverse Events in the As-Treated Population^a

AE=adverse event; CI=confidence interval; N=number of patients in the as-treated population; n=number of patients reporting at least 1 event; SAE=serious adverse event; VTE=venous thromboembolic events.

^aPatients are counted for each category regardless of the number of events.