E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to Moderate coronavirus disease 2019 (COVID-19) |
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E.1.1.1 | Medical condition in easily understood language |
COVID-19 is an infectious disease caused by coronavirus strain. Coronavirus is mainly transmitted from person to person through droplets generated when an infected person coughs, sneezes, or exhales. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084401 |
E.1.2 | Term | COVID-19 respiratory infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of RO7496998 (AT-527) compared with placebo based on the time to alleviation or improvement of COVID-19 symptoms |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of RO7496998 (AT-527) compared with placebo based on: Time to alleviation of symptoms Time to one-category improvement of baseline presenting COVID-19 symptoms Time to alleviation of individual symptoms Proportion of patients requiring hospitalization for COVID-19 Proportion of patients with >=1 COVID-19 related medically attended visit through to study end Duration of fever Frequency of COVID-19 related complications, Proportion of patients with any post-treatment infection Proportion of patients with all-cause mortality -To evaluate the antiviral activity of RO7496998 (AT-527) compared with placebo -To evaluate the safety of RO7496998 (AT-527) compared with placebo -To characterize the pharmacokinetic (PK) profile of AT-511 and major metabolites in plasma
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age >=18 years (regardless of weight) at the time of signing informed consent or age >=12 to <18 years (weight >=40 kilogram) at the time of signing informed consent (and assent) Ability to comply with all aspects of the study protocol, including providing samples for virology, in the opinion of the investigator At least three of the following symptoms of at least moderate (score >=2 as per COVID-19 Symptom Diary) intensity: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills or sweats, feeling hot or feverish, nausea, vomiting, or diarrhea Positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) diagnostic test (reverse-transcriptase polymerase chain reaction [RT-PCR] or validated rapid antigen test) <=72 hours prior to randomization Symptoms consistent with mild or moderate COVID-19, as determined by the Investigator, with onset <=5 days before randomization For women of childbearing potential and girls at or beyond menarche (age >=12 to <18 years): agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 30 days after the final dose of RO7496998 (AT-527)
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E.4 | Principal exclusion criteria |
Clinical signs indicative of COVID-19 illness requiring hospitalization Admitted to a hospital prior to randomization or is hospitalized (inpatient) at randomization due to COVID-19 In the opinion of the investigator, is likely to experience imminent deterioration and require hospitalization Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization Treatment with a COVID-19 therapeutic agent against SARS-CoV-2 including, but not limited to, other direct or indirect acting antivirals, dexamethasone, interferons, convalescent plasma, monoclonal antibodies against SARS CoV-2, intravenous immunoglobulin or other emergency use authorization (EUA)-approved treatments within the last 2 weeks prior to the screening visit Concomitant use of P-glycoprotein (P-gp) inhibitors or inducers Known allergy or hypersensitivity to components of study drug Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the final dose of RO7496998 (AT-527) Abnormal laboratory test results at screening Requirement of any prohibited medications during the study Known active viral or bacterial infection at the time of screening Any clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, could jeopardize the safety of the patient or affect patient compliance or safety/efficacy observations during the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to alleviation or improvement of COVID-19 symptoms (Items 1-12 of the COVID-19 symptom diary) maintained for a duration of 21.5 hours
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Time to alleviation of symptoms defined as the time from randomization to the point at which the following criterion is met and maintained for at least 21.5 hours: Score of 0 or 1 for Items 1-12 of the COVID-19 Symptom Diary 2. Time to one-category improvement of baseline presenting COVID-19 symptoms maintained for a duration of 21.5 hours defined as time from randomization to when the symptoms have improved by at least one category from baseline on the Likert scale 3. Time to alleviation of individual symptoms, defined as the time from randomization to the point at which the following criterion is met and maintained (for each individual symptom) for at least 21.5 hours: Score of 0 or 1 for Items 1-14 of the COVID-19 Symptom Diary 4. Proportion of patients requiring hospitalization for COVID-19 5. Proportion of patients with >=1 COVID-19 related medically attended visit through to study end (defined as hospitalization, emergency room [ER] visit, urgent care visit, physician’s office visit, or telemedicine visit, with the primary reason for the visit being COVID-19) 6.Duration of fever (time to return to afebrile state [temperature <=37.5 degrees celsius] and remaining so for at least 21.5 hours) 7.Frequency of COVID-19 related complications 8.Proportion of patients with any post-treatment infection 9.Proportion of patients with all-cause mortality 10.Change from baseline in amount of SARS-CoV-2 virus RNA, as measured by (reverse-transcriptase quantitative polymerase chain reaction) RT-qPCR at each timepoint 11.Time to cessation of SARS-CoV-2 viral shedding, as measured by RT-qPCR 12. Proportion of patients positive for SARS-Cov-2 virus RNA, as measured by RT-qPCR at specified timepoints 13. Area under the curve in the amount of SARS-CoV-2 virus RNA, as measured by RT-qPCR 14.Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0 15. Incidence of serious adverse events. 16.Change from baseline in vital signs, including peripheral capillary oxygen saturation (SpO^2) 17.Change from baseline in targeted clinical laboratory test results 18.Plasma concentration of AT-511 (the free base form of RO7496998 [AT-527]), AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010) at specified timepoints
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Day 1 to day 29 4-5. Up to day 33 6. Day 1 to day 29 7-9. Up to day 33 10-13. Day 1 to day 14 14-15. Up to day 33 16. Screening (Day -2 to -1) to day 14 17. Screening (Day -2 to -1) and day 5 18. At Days 1, 5 and 7
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Colombia |
Japan |
Mexico |
Peru |
Russian Federation |
Serbia |
Turkey |
Ukraine |
United States |
Belgium |
Denmark |
France |
Germany |
Hungary |
Italy |
Poland |
Portugal |
Romania |
Spain |
Switzerland |
Argentina |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |