| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Mild/moderate coronavirus disease 2019 (COVID-19) |
|
| 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 | 23.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10084268 |
| E.1.2 | Term | COVID-19 |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 | 10021881 - Infections and infestations |
|
| 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 |
| Evaluate the efficacy of two dose levels of intramuscular (IM) VIR-7831 versus (vs) intravenous (IV) VIR-7831 in preventing the progression of mild/moderate COVID-19 |
|
| E.2.2 | Secondary objectives of the trial |
1-Describe safety and tolerability of IM and IV VIR-7831
2-Assess VIR-7831 immunogenicity
3-Evaluate two dose levels efficacy of IM vs IV VIR-7831 on mild/moderate COVID-19 progression
4-Evaluate two dose levels efficacy of IM vs IV VIR-7831 in preventing COVID-19 respiratory disease progression
5-Compare VIR-7831 virologic activity given IM (two dose leves) or IV in reducing SARS-CoV-2 viral load
6-Assess VIR-7831 pharmacokinetics in serum following IV and IM administration
7-Describe effect of two dose levels of IM vs IV VIR-7831 on incidence and duration of time on total hospital length of stay, incidence and duration of time on a ventilator, and ICU length of stay
8-Monitor SARS-CoV-2 resistant mutants against VIR-7831
9-Compare VIR-7831 virologic activity given IM (two dose leves) or IV in reducing SARS-CoV-2 viral load
10-Compare effect of different sample collection methods in SARS-CoV-2 viral load
11-Evaluate VIR-7831 effect on the development of SARS-CoV-2 antibodies |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Saliva SARS-CoV-2 qRT-PCR sub-study
To evaluate the comparability of SARS-CoV-2 quantitative RT-PCR when performed on saliva versus nasopharyngeal (NP) swabs, an optional sub-study will be performed. Up to 200 subjects will have paired saliva and NP collected at 4 timepoints during the study (D1, D8, D15, D22). |
|
| E.3 | Principal inclusion criteria |
AGE AND RISK FACTORS
1. Participant must be aged 12 years or older at time of consent AND at high risk of progression of COVID-19 based on the presence of one or more of the following risk factors:
a. For 12-17 years old: diabetes, obesity (BMI ≥85th percentile for age/gender based on CDC growth charts), chronic kidney disease (e.g. eGFR <60), sicklecell disease, congenital heart disease, neurodevelopmental disorders, chronic lung diseases (i.e. chronic obstructive pulmonary disease, moderate to severe asthma requiring steroids, interstitial lung disease, cystic fibrosis, and pulmonary hypertension), immunosuppressive disease or immunosuppressive medications, or chronic liver disease
b. For 18-54 years old: diabetes (requiring medication), obesity (BMI ≥ 30, chronic kidney disease (i.e., eGFR <60 by MDRD), congenital heart disease, congestive heart failure (NYHA class II or more), chronic lung diseases (i.e. chronic obstructive pulmonary disease, moderate to severe asthma requiring steroids, interstitial lung disease, cystic fibrosis, and pulmonary hypertension), sickle cell disease, neurodevelopmental disorders, immunosuppressive disease or receiving immunosuppressive medications, or chronic liver disease
OR
2. Participant ≥ 55 years old, irrespective of co-morbidities
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS
3. Participants who have a positive SARS-CoV-2 test result within 7 days of randomization (by any validated diagnostic test e.g. RT-PCR, antigen based testing on any specimen type)
AND
4. Oxygen saturation ≥94% on room air
AND
5. Have symptoms of COVID-19 defined by one or more of the following: fever, chills, cough, sore throat, malaise, headache, joint or muscle pain, change in smell or taste, vomiting, diarrhea, shortness of breath on exertion
AND
6. Participant to be dosed less than or equal to 7 days from onset of symptoms to dosing day (D1)
SEX AND CONTRACEPTIVE/BARRIER REQUIREMENTS
7. No gender restrictions
8. Female participants must meet and agree to abide by the following contraceptive criteria. Contraception use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
a. Is a woman of non-childbearing potential (WONCBP).
OR
b. Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, during the study intervention period and for up to 24 weeks after the last dose of study intervention.
The investigator should evaluate potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention.
-If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the
participant must be excluded from participation if the serum pregnancy result is positive.
INFORMED CONSENT
9. Capable of giving signed informed consent.
OR
10. If participants are not capable of giving written informed consent, alternative consent procedures will be followed as defined in Section 10.1.3 of protocol.
OR
11. Participants <18 years old will be required to sign an assent form in addition to a parent or guardian signing the informed consent. |
|
| E.4 | Principal exclusion criteria |
MEDICAL CONDITIONS
1. Currently hospitalized or judged by the investigator as likely to require hospitalization in the next 24 hours
2. Symptoms consistent with severe COVID-19 as defined by shortness of breath at rest or respiratory distress or requiring supplemental oxygen
3. Participants who, in the judgement of the investigator are likely to die in the next 7 days.
4. Known hypersensitivity to any constituent present in the investigational product
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE
5. Enrollment in any investigational vaccine study within the last 180 days or any other investigational drug study within 30 days prior to Day 1 or within 5 half-lives of the investigational compound, whichever is longer
6. Enrollment in any trial of an investigational drug, vaccine or device study for SARS-CoV-2/COVID-19 within 90 days prior to Day 1 or within 5 half-lives of the investigational compound, whichever is longer
OTHER EXCLUSIONS
7. Receipt of convalescent plasma from a recovered COVID-19 patient or anti SARS-CoV-2 mAb within the last 3 months.
8. Participants who, in the judgment of the investigator, will be unlikely or unable to comply with the requirements of the protocol through Day 29
NOTE: Previous receipt of a SARS-CoV-2/COVID-19 vaccine is NOT an exclusion criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression of COVID-19 through Day 29 as defined by hospitalization > 24 hours for acute management of illness due to any cause or death. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
•Occurrence of adverse events (AEs)
•Occurrence of serious adverse events (SAEs)
•Occurrence of adverse events of special interest (AESI)
•Incidence and titers (if applicable) of serum anti-drug antibody (ADA) to VIR-7831 (sotrovimab)
•Progression of COVID-19 through Day 29 as defined by visit to a hospital emergency room for management of illness OR hospitalization for acute management of illness for any duration and for any cause OR death
•Development of severe and/or critical respiratory COVID-19 as manifested by
requirement for respiratory support (including oxygen) at Day 8, Day 15, Day 22, and Day 29
•Mean area under the curve of SARSCoV-2 viral load in nasal secretions as measured by qRT-PCR from Day 1 to Day 8 (AUCD1-8)
•Change from baseline in viral load in nasal secretions by qRT-PCR at Day 8
•Proportion of participants with a persistently high SARS-CoV-2 viral load at Day 8 by qRT-PCR
•IV and IM sotrovimab pharmacokinetics (PK) in serum
•Incidence of hospitalization through Day 29
•Total hospital length of stay
•Proportion of participants requiring ICU stay or mechanical ventilation through Day 29
•Total ICU LOS
•SARS-CoV-2 resistance mutants to sotrovimab at baseline
•Emergence of viral resistance mutants to mAb by SARS-CoV-2
•Change from baseline in viral load in nasal secretions by qRT-PCR during follow-up period at Day 5, Day 11, Day 15, Day 22 and Day 29
• Undetectable SARS-CoV-2 in nasal secretions by qRT-PCR at Day 3, Day 5, Day 8, Day 11, Day 15, Day 22 and Day 29
• Mean area under the curve of SARSCoV-2 viral load as measured by qRT-PCR from Day 1 to Day 5 (AUCD1-5) and Day 1 to 11 (AUCD1-11) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1 to Day 5
Day 1 to Day 8
Day 1 to Day 11
Day 3
Day 5
Day 8
Day 11
Day 15
Day 22
Day 29
Note: Timepoints are specified for secondary end points in section E.5.2 of this document. |
|
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Two dose levels of intramuscular VIR-7831 are compared versus one dose of intravenous VIR-7831 |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| 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 |
| Canada |
| India |
| Moldova, Republic of |
| Peru |
| South Africa |
| Ukraine |
| United States |
| Austria |
| France |
| Italy |
| Poland |
| Romania |
| Spain |
| Argentina |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| A participant is considered to have completed the study if he/she has completed the Week 24 visit. The end of the study is defined as the date of the last contact of the last participant in the study. |
|
| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | 12 |
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 12 |
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