Published Data — Randomized, Double-blind, Placebo-controlled Trial

Remdesivir for the Treatment of Covid-19

ACTT-1—Final Report (Multinational)

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1):
Study Design
Study Design
• Background: A multicenter, double-blind, randomized, placebo-controlled trial of
intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower
respiratory tract involvement during February 21-April 19, 2020.
• Location: 73 sites in the United States, Europe, Asia, and Mexico
• Inclusion Criteria (n = 1062)
- Age ≥18 years
- Hospitalized
- Lab confirmed SARS-CoV-2 (PCR or other public health assay) <72 hours of enrollment
- One or more of the following:
- Pulmonary infiltrates on chest imaging
- Rales or crackles on exam AND SpO2 ≤94% on room air
- Requiring mechanical ventilation or supplementary oxygen
• Exclusion Criteria
- Pregnant or breastfeeding
- AST/ALT >5x ULN
- eGFR <30

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1):
Study Design

Study Design
• Primary Outcome: Time to recovery (discharge or no longer requiring supplemental O 2)*
• Secondary outcomes:
- Mortality at days 14 and 28
- Grade 3 or 4 adverse events, or severe adverse events

* This primary outcome was changed from an earlier primary outcome of recovery at day 15 as
evolving clinical information showed the prolonged course of COVID-19 disease. None of the
preliminary data was known at the time of this decision

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1):
Study Design

Arms and Interventions (1:1 randomization stratified by disease severity and site)

Remdesivir
200 mg loading dose on day 1, then 100 mg maintenance dose daily on days 2-10
(n = 541)
or
Placebo
Volume equivalent loading and maintenance doses
(n = 521)

*If the hospital had a written policy or guideline, participants could receive other experimental or
off-label treatments for COVID-19. Otherwise, other specific treatments were prohibited from study
day 1 through day 29.

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1): Safety

• In the remdesivir arm, 98.2% received the drug as assigned

- 36 patients discontinued due to an adverse event

• In the placebo arm, 99.2% completed infusions as assigned

- 36 patients discontinued due to an adverse event

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1):
Baseline Characteristics

Remdesivir Placebo
Baseline Characteristics
(n = 541) (n = 521)

Age, years (mean ± SD) 58.6 ± 14.6 59.2 ± 15.4

Male, n (%) 352 (65.1) 332 (63.7)

Coexisting conditions, n/total (%)

Hypertension 269/532 (50.6) 264/519 (50.9)

Obesity 242/531 (45.6) 234/518 (45.2)

Type 2 Diabetes 164/532 (30.8) 158/519 (30.4)

Duration of symptoms prior to

9 (6 - 12) 9 (7 - 13)
randomization, days (median, IQR)

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1):
Baseline Characteristics

Remdesivir Placebo
Baseline Characteristics
(n = 541) (n = 522)

Illness score on ordinal scale n (%)

4. Hospitalized, not receiving

supplemental O2 75 (13.9) 63 (12.1)

5. Hospitalized, receiving
supplemental O2 232 (42.9) 203 (39.0)

6. Hospitalized, non-invasive
ventilation or high-flow O2 devices 95 (17.6) 98 (18.8)

7. Hospitalized, invasive mechanical

131 (24.2) 154 (29.6)
ventilation, or ECMO

Baseline score missing 8 (1.5) 3 (0.6)

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1):
Results

• Median time to recovery was significantly different:

- Remdesivir 10 days (95% confidence interval [CI], 9 to 11)
- Placebo 15 days (95% CI, 13 to 18) in those who received
placebo
- Rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001)

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
M o r t a l i t y (K a p l a n - M e i e r E s ti m a t e )
Remdesivir for the Treatment of Covid-19 (ACTT-1):
Results, Mortality by Days 15 and 29 (Kaplan-Meier Estimate)

Remdesivir Placebo
20

15
13.0
11.9

10
7.7
6.7

5
2.9
1.6
0
Overall Mild-Moderate Severe
Baseline Disease Severity

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1):
D a y s to R e c o v e r y (M e d ia n )
Results, Days to Recovery

Remdesivir Placebo
25

20 P<0.00
1 18
15
15
11
10
10

5 5
5

0
Overall Mild-Moderate Severe
Baseline Disease Severity

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19 (ACTT-1):
Morality Results

Outcome* *Hazard Ratio (95% CI)

Mortality (Overall) 0.73 (0.52 – 1.03)

Mortality, by ordinal score at baseline
4 0.82 (0.17 – 4.07)
5 0.30 (0.14 – 0.64)
6 1.02 (0.54 – 1.91)
7 1.13 (0.67 – 1.89)

*Hazard ratio based on comparison of remdesivir versus placebo

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]
Remdesivir for the Treatment of Covid-19:
Authors’ Conclusions

Conclusions: “Our data show that remdesivir was superior to

placebo in shortening the time to recovery in adults who were
hospitalized with Covid-19 and had evidence of lower respiratory
tract infection.”

Source: Beigel JH, et al. N Engl J Med. October 8, 2020. [Online ahead of print]