PROTOCOL SUMMARY Synopsis
Title: A randomized, multi-center, double-blind, placebo-controlled study to assess the safety and efficacy of monoclonal antibody VIR-7831 for the early treatment of coronavirus disease 2019 (COVID-19) in non-hospitalized patients
Rationale:
There is an urgent medical need for therapeutics for the treatment of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019 (COVID-19). Early treatment of mild and moderate disease in outpatients could prevent the more severe sequelae of COVID-19 requiring hospitalization, such as respiratory failure, thromboembolic disease leading to pulmonary embolism and stroke, arrhythmias, and shock. Furthermore, a potent treatment given early in disease could ameliorate the severity and duration of COVID-19 and potentially reduce transmission.
Vir Biotechnology, Inc. (Vir) has developed a fully human neutralizing anti-SARS-CoV-2 antibody (Pinto et al. 2020), VIR-7831 (GSK4182136), which has an Fc-modification (“LS”) that is designed to improve bioavailability in the respiratory mucosa (Hope et al. 2019) and increase half-life (Ko et al. 2014).
The Lead-In phase of this study will serve as the first-in-human (FIH) assessment and includes participants with mild/moderate COVID-19 to assess the safety and tolerability of VIR-7831. Following initial safety assessment in the Lead-In phase, assessment of safety and efficacy will commence in the Expansion phase of this study with the aim of preventing disease progression in high-risk participants.
The Expansion phase of the study will progress following assessment of available unblinded safety data from the Lead-in phase (N=10 per arm through Day 15 of follow- up) by an IDMC. Outpatient participants with early mild/moderate COVID-19 who are at high risk for progression to severe disease will be randomized in a 1:1 ratio to receive a single IV infusion of VIR-7831 or placebo.
Participants will be monitored through at least 2 hours post-dose prior to discharge from the study unit. During dose administration vital signs will be monitored every 15 minutes over the 1-hour IV infusion. Vital signs will also be monitored every hour after infusion for 2 hours. Participants will subsequently be actively monitored on an outpatient basis with in-person study visits at Weeks 1, 2, 3, and 4 and daily telephone calls (except on in- clinic visit days) through Day 15 for AEs and worsening of COVID-19. Serum PK and anti-drug antibodies (ADA) samples will be collected as detailed in the Schedule of Activities (Section 1.3, Table 2).
Starting at Week 8, participants will be monitored monthly via phone call to assess for the incidence and of severity of subsequent COVID-19 illness, if any, for a total of
24 weeks from dosing.
Original
11
VIR-7831 CONFIDENTIAL
Immunology Assessment Sub-study
Participants in the Lead-In phase will have blood collections for the isolation of peripheral blood mononuclear cells (PBMCs) as part of the required sub-study to explore the host immune response and potential biomarkers of infection.
At select participating sites in the Expansion Phase, participants may consent to an optional sub-study. Subjects who consent to the optional sub-study will have blood collection for the isolation of PBMCs.
The timepoints for blood collection for the sub-study are outlined in the Schedule of Activities (Section 1.3, Table 2). The sub-study will be done at selected sites in the United States only. All 20 subjects in the Lead-In Phase will participate in the sub-study. Approximately, 40-100 participants will be enrolled in the optional sub-study in the Expansion Phase.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
5.1.1.
1.
OR 2.
5.1.2.
3.
Age and Risk Factors
Participant must be aged 18 years or older AND at high risk of progression of COVID-19 based on presence of one or more of the following risk factors: diabetes (requiring medication), obesity (BMI>30), chronic kidney disease
(i.e., eGFR <60 by MDRD), congestive heart failure (NYHA class II or more), chronic obstructive pulmonary disease (history of chronic bronchitis, chronic obstructive lung disease, or emphysema with dyspnea on physical exertion), and moderate to severe asthma (participant requires an inhaled steroid to control symptoms or has been prescribed a course of oral steroids in the past year)
Participant ≥ 55 years old, irrespective of co-morbidities.
Type of Participant and Disease Characteristics
Participants who have a positive SARS-CoV-2 test result (by any validated test e.g. RT-PCR on any specimen type)
AND
Oxygen saturation ≥94% on room air
AND
Have COVID-19 defined by one or more of the following symptoms: fever, chills, cough, sore throat, malaise, headache, joint or muscle pain, change in smell or taste, vomiting, diarrhea, shortness of breath on exertion
Medication Not Permitted During the Study
Given accumulating evidence around the risks associated with the use of hydroxychloroquine and chloroquine and absence of defined benefit, these will NOT be considered standard of care, and are prohibited over the course of the study.
Receipt of convalescent plasma from a recovered COVID-19 patient or anti-SARS-CoV-2 mAb is also not permitted during the study.
Receipt of any vaccine is not permitted within 4 weeks after dosing. Receipt of any investigational SARS-CoV-2 vaccine is not permitted during the study.