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NCT04709835

Study to Evaluate the Effects of AT-527 in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19

Completed Phase 2 Results posted Last updated 26 October 2022
What this trial tests

Phase 2 trial testing AT-527 in COVID-19 in 104 participants. Completed in 13 October 2021.

Timeline
3 February 2021
Primary endpoint
17 September 2021
13 October 2021

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment104
Start date3 February 2021
Primary completion17 September 2021
Estimated completion13 October 2021
Sites12 locations across Greece, Ireland, United Kingdom, Canada, Spain, Latvia

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo Primary · Baseline, Day 3, Day 5, Day 7

SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from nasopharyngeal (NP) swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement.

Day 3
GroupValue95% CI
Placebo Matched to AT-527 550 mg-1.16± 0.203
AT-527 550 mg (1x550 mg)-1.26± 0.206
Day 5
GroupValue95% CI
Placebo Matched to AT-527 550 mg-2.42± 0.230
AT-527 550 mg (1x550 mg)-2.11± 0.226
Day 7
GroupValue95% CI
Placebo Matched to AT-527 550 mg-3.13± 0.220
AT-527 550 mg (1x550 mg)-3.38± 0.220
Time to Cessation of SARS-CoV-2 Viral Shedding Secondary · Up to Day 7

Time to cessation of viral shedding was defined as the time between the initiation of any study treatment and the first time when a negative or below the limit of detection RT-PCR test result was obtained. RT-PCR was measured from NP swabs. Median, 25th and 75th percentiles were estimated from the Kaplan-Meier curve.

GroupValue95% CI
Pooled PlaceboNA144.2 – NA
AT-527 550 mg (1x550 mg)NA143.8 – NA
AT-527 1100 mg (4x275 mg)NA141.1 – NA
Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA Secondary · Up to Day 7

Time to sustained non-detectable SARS-CoV-2 virus RNA was defined as the time between the initiation of any study treatment and first time when a negative or below the limit of detection test result by RT-PCR is obtained after which no positive test above or equal to the limit of detection was reported. RT-PCR was measured from NP swabs. Median, 25th and 75th percentiles were estimated from the Kaplan-Meier curve.

GroupValue95% CI
Pooled PlaceboNANA – NA
AT-527 550 mg (1x550 mg)NANA – NA
AT-527 1100 mg (4x275 mg)NANA – NA
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints Secondary · Baseline, Day 3, Day 5, Day 7

Reported here is the percentage of participants with a positive virus RNA by RT-PCR test result above or equal to the limit of quantification (LOQ). RT-PCR was measured from NP swabs.

Baseline
GroupValue95% CI
Pooled Placebo100
AT-527 550 mg (1x550 mg)100
AT-527 1100 mg (4x275 mg)96.7
Day 3
GroupValue95% CI
Pooled Placebo95.0
AT-527 550 mg (1x550 mg)100
AT-527 1100 mg (4x275 mg)93.1
Day 5
GroupValue95% CI
Pooled Placebo84.2
AT-527 550 mg (1x550 mg)90.0
AT-527 1100 mg (4x275 mg)83.3
Day 7
GroupValue95% CI
Pooled Placebo76.9
AT-527 550 mg (1x550 mg)79.3
AT-527 1100 mg (4x275 mg)76.7
Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA Secondary · Baseline, Day 3, Day 5, Day 7

AUC is the amount of SARS-CoV-2 virus RNA from baseline to the last sample timepoint and was calculated using the trapezoidal method. RT-PCR was measured from NP swabs.

GroupValue95% CI
Pooled Placebo651.56± 189.10
AT-527 550 mg (1x550 mg)733.70± 146.63
AT-527 1100 mg (4x275 mg)618.62± 194.88
Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) Secondary · Up to 28 Days

COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).Time to alleviation or improvement is defined as the length of time taken from start of treatment to the point at which all of the following three criteria are met and maintained for a concurren

GroupValue95% CI
Pooled Placebo43.49.3 – 104.7
AT-527 550 mg (1x550 mg)57.29.0 – 115.8
AT-527 1100 mg (4x275 mg)56.42.5 – 96.4
Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) Secondary · Up to 28 Days

COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation or improvement is defined as the length of time taken from start of treatment to the point at which all of the following three criteria are met and maintained for a concurre

GroupValue95% CI
Pooled Placebo43.49.3 – 104.7
AT-527 550 mg (1x550 mg)57.29.0 – 141.2
AT-527 1100 mg (4x275 mg)58.12.5 – 118.2
Time to Alleviation of COVID-19 Symptoms (21.5 Hours) Secondary · Up to 28 Days

COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation of COVID-19 symptoms is defined as the length of time taken from start of treatment to the point at which the following criterion is met and maintained for at least 21.5 hou

GroupValue95% CI
Pooled Placebo43.49.3 – 104.7
AT-527 550 mg (1x550 mg)57.29.0 – 115.8
AT-527 1100 mg (4x275 mg)56.48.2 – 96.4
Time to Alleviation of COVID-19 Symptoms (43 Hours) Secondary · Up to 28 Days

COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation of COVID-19 symptoms is defined as the length of time taken from start of treatment to the point at which the following criterion is met and maintained for at least 43 hours

GroupValue95% CI
Pooled Placebo43.49.3 – 104.7
AT-527 550 mg (1x550 mg)57.29.0 – 141.2
AT-527 1100 mg (4x275 mg)58.18.2 – 118.2
Duration of Fever Secondary · Up to 28 Days

Duration of fever was defined as the time from start of treatment to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours.

GroupValue95% CI
Pooled Placebo10.69.6 – 11.7
Percentage of Participants With COVID-19 Related Complications Secondary · Up to 33 Days

COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis, myocarditis, and cardiac failure.

GroupValue95% CI
Pooled Placebo0
AT-527 550 mg (1x550 mg)3.3
AT-527 1100 mg (4x275 mg)3.3
Time to Alleviation of an Individual Symptom Secondary · Up to 28 Days

The COVID-19 Symptom Diary included the following 14 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, diarrhea, sense of smell over the past 7 days and sense of taste over the past 7 days. The severity of items 1-12 was recorded on a 4-point Likert scale (none=0, mild=1, moderate=2, severe=3). Items 13-14 were recorded on a 3-point Likert scale (same as usual=0, less than usual=1, no sense=2). Time to alleviation of an individual symptom was defined as the time take

Nasal Congestion/Runny Nose
GroupValue95% CI
Pooled Placebo27.611.3 – 59.9
AT-527 550 mg (1x550 mg)34.215.8 – 82.4
AT-527 1100 mg (4x275 mg)32.710.0 – 57.7
Sore Throat
GroupValue95% CI
Pooled Placebo20.514.1 – 22.7
AT-527 550 mg (1x550 mg)24.19.8 – 45.0
AT-527 1100 mg (4x275 mg)111.722.1 – 201.4
Cough
GroupValue95% CI
Pooled Placebo22.611.8 – 129.3
AT-527 550 mg (1x550 mg)90.723.7 – 140.4
AT-527 1100 mg (4x275 mg)33.920.5 – 119.2
Shortness of Breath
GroupValue95% CI
Pooled Placebo23.911.5 – NA
AT-527 550 mg (1x550 mg)68.968.5 – 69.2
AT-527 1100 mg (4x275 mg)11.611.6 – 11.6
Aches and Pains
GroupValue95% CI
Pooled Placebo33.111.8 – 60.4
AT-527 550 mg (1x550 mg)22.316.3 – 62.2
AT-527 1100 mg (4x275 mg)94.448.1 – 177.7
Fatigue
GroupValue95% CI
Pooled Placebo47.822.6 – 178.1
AT-527 550 mg (1x550 mg)44.410.5 – 94.5
AT-527 1100 mg (4x275 mg)70.622.6 – 106.0
Headache
GroupValue95% CI
Pooled Placebo32.010.1 – 95.8
AT-527 550 mg (1x550 mg)11.79.8 – 93.6
AT-527 1100 mg (4x275 mg)34.421.8 – 105.4
Chills/Sweats
GroupValue95% CI
Pooled Placebo11.89.8 – 24.1
AT-527 550 mg (1x550 mg)12.09.0 – 35.8
AT-527 1100 mg (4x275 mg)25.017.1 – 41.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 33 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pooled Placebo
Serious: 1/40 (3%)
Deaths: 0/40
AT-527 550 mg (1x550 mg)
Serious: 1/30 (3%)
Deaths: 0/30
AT-527 1100 mg (4x275 mg)
Serious: 1/30 (3%)
Deaths: 0/30

Serious adverse events (2 terms)

ReactionSystemPooled PlaceboAT-527 550 mg (1x550 mg)AT-527 1100 mg (4x275 mg)
Atrial flutterCardiac disorders
COVID-19 pneumoniaInfections and infestations
Other adverse events (2 terms — click to expand)

ReactionSystemPooled PlaceboAT-527 550 mg (1x550 mg)AT-527 1100 mg (4x275 mg)
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders

Most-reported serious reactions: Atrial flutter, COVID-19 pneumonia.

Data from ClinicalTrials.gov NCT04709835 adverse events section.

Sponsor's own description

This randomized study evaluates the antiviral activity, safety, efficacy and pharmacokinetics of AT-527 versus a placebo in participants with mild or moderate coronavirus disease (COVID-19) who are not hospitalized.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. SARS-CoV-2 Antiviral Therapy.
    Tao K, Tzou PL, Nouhin J, Bonilla H, et al · · 2021 · cited 80× · PMID 34319150 · DOI 10.1128/cmr.00109-21
  2. Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review.
    Hu S, Jiang S, Qi X, Bai R, et al · · 2022 · cited 68× · PMID 34762760 · DOI 10.1002/ddr.21895
  3. An update of anti-viral treatment of COVID-19
    Şimşek-Yavuz S, Komsuoğlu Çelikyurt FI. · · 2021 · cited 51× · PMID 34391321 · DOI 10.3906/sag-2106-250
  4. Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021.
    Alam S, Kamal TB, Sarker MMR, Zhou JR, et al · · 2021 · cited 31× · PMID 34220503 · DOI 10.3389/fphar.2021.659577
  5. Progress and pitfalls of a year of drug repurposing screens against COVID-19.
    Sourimant J, Aggarwal M, Plemper RK. · · 2021 · cited 23× · PMID 34218010 · DOI 10.1016/j.coviro.2021.06.004
  6. Deuterated Drugs and Biomarkers in the COVID-19 Pandemic.
    Jansen-van Vuuren RD, Jedlovčnik L, Košmrlj J, Massey TE, et al · · 2022 · cited 20× · PMID 36440130 · DOI 10.1021/acsomega.2c04160
  7. Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences.
    Shiraki K, Sato N, Sakai K, Matsumoto S, et al · · 2022 · cited 20× · PMID 35121001 · DOI 10.1016/j.pharmthera.2022.108121
  8. Oral bemnifosbuvir (AT-527) vs placebo in patients with mild-to-moderate COVID-19 in an outpatient setting (MORNINGSKY).
    Horga A, Saenz R, Yilmaz G, Simón-Campos A, et al · · 2023 · cited 12× · PMID 37928891 · DOI 10.2217/fvl-2023-0115

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