ACTT-1 Study (mild/moderate & severe COVID-19)

VEKLURY improved clinical outcomes in hospitalized patients across a spectrum of COVID-19 disease severity1-4

ACTT-1 Study trial design

The ACTT-1 study was a randomized, double-blind, placebo-controlled, phase 3 clinical trial in hospitalized adult patients with confirmed SARS-CoV-2 infection and mild, moderate, or severe COVID-19.

ACTT-1 Study N=1062
R 1:1
n=541
n=521
VEKLURY 200 mg
Placebo 200 mg
VEKLURY 100 mg daily
Placebo 100 mg daily

Treatment with VEKLURY® (remdesivir) was stopped in patients who were discharged from the hospital prior to the completion of 10 days of treatment.

Primary endpoint: time to recovery by Day 29 based on ordinal scale

Time to recovery was assessed within 29 days after randomization. Recovery was defined as discharged from the hospital without limitations on activities, discharged from the hospital with limitations on activities and/or requiring home oxygen, or hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care.

Baseline characteristics

Characteristic VEKLURY(n=541) Placebo(n=521)
Mean age ± SD 58.6±14.6 59.2±15.4
Male sex 65.1% 63.7%
Race
White 51.6% 55.1%
Black 20.1% 22.5%
Asian 14.6% 10.7%
Ethnicity: Hispanic/Latinx 24.8% 22.3%
Mild/moderate disease* 10% 10%
Severe disease 90% 90%
Respiratory Status
Low-flow oxygen 42.9% 39.0%
High-flow oxygen 17.6% 18.8%
Invasive mechanical ventilation/ECMO 24.2% 29.6%
Comorbidities
Hypertension 50.6% 50.9%
Obesity 45.6% 45.2%
Type 2 diabetes mellitus 30.8% 30.4%

*Defined by SpO2 >94% and respiratory rate <24 breaths/minute without supplemental oxygen.

Defined by a requirement for the following: mechanical ventilation, oxygen requirement, SpO2 ≤94% on room air, or respiratory rate ≥24 breaths/minute.

VEKLURY helped shorten time to recovery

Patients with COVID-19 experienced significantly shorter recovery times with VEKLURY in the overall study population by Day 29
ACTT-1 Recovery Time Data image

Recovery, which included hospital discharge for some patients with or without limitations on activities, was defined as ordinals 1 to 3.

8-point ordinal scale

RECOVERY
1
not hospitalized, no limitations on activities
2
not hospitalized, limitation on activities and/or requiring home oxygen
3
hospitalized, not requiring supplemental oxygen–no longer requires ongoing medical care
4
hospitalized, not requiring supplemental oxygen–requiring ongoing medical care (COVID-19 related or otherwise)
5
hospitalized, requiring supplemental oxygen
6
hospitalized, on noninvasive ventilation or high-flow oxygen devices
7
hospitalized, on invasive mechanical ventilation or ECMO
8
death
Treatment with VEKLURY earlier in the disease course resulted in the greatest benefit for patients

A prespecified subgroup analysis showed:

  • In patients with symptom onset ≤10 days (n=676), median time to recovery was 9 days with VEKLURY vs 15 days with placebo (recovery rate ratio: 1.37 [95% Cl, 1.14-1.64])
  • In patients with symptom onset >10 days (n=383), median time to recovery was 11 days with VEKLURY vs 15 days with placebo (recovery rate ratio: 1.20 [95% Cl, 0.94-1.52])

IMPORTANT SAFETY INFORMATION

Contraindication

  • VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.

Please see additional Important Safety Information below.

The efficacy of VEKLURY was proven across a variety of secondary clinical endpoints

Patients had a significantly greater likelihood of improvement in clinical status with VEKLURY
  • A key secondary endpoint was clinical status of patients on Day 15 as assessed by an 8-point ordinal scale

Patients were

more likely to have improved clinical status

with VEKLURY vs placebo at Day 15

Improvements were maintained through Day 29 (odds ratio: 1.54 [95% CI, 1.25-1.91])

VEKLURY reduced progression to mechanical ventilation or ECMO
13% VEKLURY
vs
23% Placebo

(95% CI, 10%-17%)

(95% CI, 19%-27%)


Significantly lower incidence of new mechanical ventilation or ECMO with VEKLURY compared with placebo in patients who were not receiving either at baseline

Mortality in the overall population

Overall mortality was a prespecified secondary endpoint in the ACTT-1 trial
  • Results in the overall population at day 29 were not statistically significant
  VEKLURY(n=541)% (n) Placebo(n=521)% (n)
Mortality by Day 15 7% (35) 12% (61)
(hazard ratio: 0.55 [95% CI, 0.36-0.83])
Mortality by Day 29 11% (59) 15% (77)
(hazard ratio: 0.73 [95% CI, 0.52-1.03])

In a post hoc subgroup analysis, VEKLURY reduced mortality rates in patients on low-flow oxygen at baseline (ordinal score 5), with the difference in other baseline ordinal subgroups not reaching statistical significance

Mortality by ordinal score at baseline
ACTT-1 Study data showing the number of patients and deaths ACTT-1 Study data showing the number of patients and deaths
  • There was no adjustment to control for multiple testing in this post hoc analysis
  • In other studies, VEKLURY was shown to have no benefit on mortality rates

 

Adverse reactions in the ACCT-1 trial

  • All adverse reactions (ARs), Grades ≥3: 41 (8%) with VEKLURY vs 46 (9%) with placebo; serious ARs: 2 (0.4%)* vs 3 (0.6%); ARs leading to treatment discontinuation: 11 (2%) vs 15 (3%)

Important Safety Information

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Contraindication

  • VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.

Warnings and precautions

  • Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of VEKLURY. Monitor patients under close medical supervision for hypersensitivity reactions during and following administration of VEKLURY. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time ≤120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue VEKLURY and initiate appropriate treatment (see Contraindications).
  • Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received VEKLURY; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing VEKLURY if ALT levels increase to >10x ULN. Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.
  • Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in the antiviral activity of VEKLURY.

Adverse reactions

  • The most common adverse reaction (≥5% all grades) was nausea.
  • The most common lab abnormalities (≥5% all grades) were increases in ALT and AST.

Drug interactions

  • Drug interaction trials of VEKLURY and other concomitant medications have not been conducted in humans.

Dosage and administration

  • Dosage: For adults and pediatric patients ≥12 years old and weighing ≥40 kg: 200 mg on Day 1, followed by once-daily maintenance doses of 100 mg from Day 2 administered only via intravenous infusion over 30 to 120 minutes.
  • Treatment duration: For patients not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 5 days; may be extended up to 5 additional days (10 days total) if clinical improvement is not observed. For patients requiring invasive mechanical ventilation and/or ECMO: 10 days.
  • Testing prior to and during treatment: Perform eGFR, hepatic laboratory, and prothrombin time testing prior to initiating VEKLURY and during use as clinically appropriate.
  • Renal impairment: VEKLURY is not recommended in individuals with eGFR <30 mL/min.
  • Dose preparation and administration: See full Prescribing Information.

Pregnancy and lactation

  • Pregnancy: There are insufficient human data on the use of VEKLURY during pregnancy. Pregnant women hospitalized with COVID-19 are at risk for serious morbidity and mortality. VEKLURY should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
  • Lactation: It is not known whether VEKLURY can pass into breast milk. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

INDICATION

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For patients hospitalized with COVID-19: VEKLURY is indicated for treatment of adults and pediatric patients ≥12 years old and weighing ≥40 kg requiring hospitalization for COVID-19. VEKLURY is indicated for the treatment of adults and pediatric patients ≥12 years old and weighing ≥40 kg requiring hospitalization for COVID-19. VEKLURY should only be administered in a hospital or healthcare setting capable of providing acute care comparable to inpatient hospital care.

For information about emergency use to treat suspected or laboratory-confirmed COVID-19 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg, please see the EUA Fact Sheet and FDA Letter of Authorization available at gilead.com/remdesivir.

Please see full Prescribing Information for VEKLURY.

COVID-19=coronavirus disease 2019; ECMO=extracorporeal membrane oxygenation; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; SD=standard deviation; SpO2=oxygen saturation.

*Seizure (n=1), infusion-related reaction (n=1).

Seizure (n=1), infusion-related reaction (n=1), transaminases increased (n=3), ALT increased and AST increased (n=1), GFR decreased (n=2), acute kidney injury (n=3).

References: 1. Veklury. Package insert. Gilead Sciences, Inc.; 2020. 2. Beigel JH, Tomashek KM, Dodd LE; for the ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19 - final report. N Engl J Med. 2020;383(19):1813-1826. 3. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19 - final report. Supplement 1. Supplementary appendix. N Engl J Med. 2020;383(19):1813-1826. Accessed January 5, 2021. https://www.nejm.org/doi/suppl/10.1056/NEJMoa2007764/suppl_file/nejmoa2007764_appendix.pdf 4. WHO Solidarity Trial Consortium. Repurposed antiviral drugs for COVID-19–interim WHO Solidarity trial results. N Engl J Med. Published online December 2, 2020. doi:10.1056/NEJMoa2023184


View All

INDICATION

View All

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For patients hospitalized with COVID-19: VEKLURY is indicated for treatment of adults and pediatric patients ≥12 years old and weighing ≥40 kg requiring hospitalization for COVID-19. VEKLURY is indicated for the treatment of adults and pediatric patients ≥12 years old and weighing ≥40 kg requiring hospitalization for COVID-19. VEKLURY should only be administered in a hospital or healthcare setting capable of providing acute care comparable to inpatient hospital care.

For information about emergency use to treat suspected or laboratory-confirmed COVID-19 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg, please see the EUA Fact Sheet and FDA Letter of Authorization available at gilead.com/remdesivir.

Please see full Prescribing Information for VEKLURY.

Important Safety Information

Collapse

Contraindication

  • VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.

Warnings and precautions

  • Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of VEKLURY. Monitor patients under close medical supervision for hypersensitivity reactions during and following administration of VEKLURY. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time ≤120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue VEKLURY and initiate appropriate treatment (see Contraindications).
  • Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received VEKLURY; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing VEKLURY if ALT levels increase to >10x ULN. Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.
  • Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in the antiviral activity of VEKLURY.

Adverse reactions

  • The most common adverse reaction (≥5% all grades) was nausea.
  • The most common lab abnormalities (≥5% all grades) were increases in ALT and AST.

Drug interactions

  • Drug interaction trials of VEKLURY and other concomitant medications have not been conducted in humans.

Dosage and administration

  • Dosage: For adults and pediatric patients ≥12 years old and weighing ≥40 kg: 200 mg on Day 1, followed by once-daily maintenance doses of 100 mg from Day 2 administered only via intravenous infusion over 30 to 120 minutes.
  • Treatment duration: For patients not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 5 days; may be extended up to 5 additional days (10 days total) if clinical improvement is not observed. For patients requiring invasive mechanical ventilation and/or ECMO: 10 days.
  • Testing prior to and during treatment: Perform eGFR, hepatic laboratory, and prothrombin time testing prior to initiating VEKLURY and during use as clinically appropriate.
  • Renal impairment: VEKLURY is not recommended in individuals with eGFR <30 mL/min.
  • Dose preparation and administration: See full Prescribing Information.

Pregnancy and lactation

  • Pregnancy: There are insufficient human data on the use of VEKLURY during pregnancy. Pregnant women hospitalized with COVID-19 are at risk for serious morbidity and mortality. VEKLURY should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
  • Lactation: It is not known whether VEKLURY can pass into breast milk. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

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