The Containing Coronavirus Disease 19 (COVID-19) Trial
Condition: SARS-CoV Infection; Interferon; Covid19
MeSH terms: COVID-19; Severe Acute Respiratory Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      In recent months severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has emerged as
      a novel human pathogen and, susceptibility amongst humans is presumed to be universal.
      Prevention measures of COVID-19 have included distancing, quarantines, use of facemasks in
      public places, and hand hygiene measures. Mandatory quarantines have also been applied on
      index cases and their contacts, as well as an active search for asymptomatic patients.

      Current strategies to reduce the spread of SARS-CoV-2 do not include measures that could
      prevent transmission prior to the onset of symptoms. Subjects infected with SARS-CoV-2 have
      been known to shed virus and be contagious for up to 5 days prior to developing symptoms
      ('pre-symptomatic transmission'). In fact, nearly 60% of all infected subjects can shed virus
      pre-symptomatically. Pre- or even asymptomatic shedding occurs across all age groups,
      contributing to the rapidly expanding pandemic.

      Post-exposure prophylaxis (PEP) using type 1 interferon (IFN) can potentially eliminate the
      spread of SARS-CoV-2. IFN could reduce the period of viral shedding by ~1 week. Since
      pre-symptomatic shedding of virus can start up to 5 days prior to symptom onset, our approach
      of a PEP intervention to all contacts recently exposed to a case could possibly entirely
      interrupt the spread of the virus, and with that, the pandemic. The current study focuses on
      prevention of the disease in addition to its treatment. Thus, the key distinction between
      these other trials and this study is that this study focuses on containing coronavirus (i.e.
      cause) in the community, rather than simply its treatment (i.e. consequence) in the
      individual.

      Viral spread could be eliminated through interventions effective at abolishing viral
      transmission. However, such post-exposure prophylaxis interventions, that is initiation of
      antiviral therapy in pre-infectious contacts to reduce or even eliminate such spread, must be
      safe since they are given to asymptomatic and possibly uninfected subjects. In none of the
      previous clinical trials of IFN therapy for SARS-CoV-2 have serious adverse events been
      recorded. Furthermore, the IFN chosen for this study (pegylated IFN 1b) has been extensively
      studied in clinical trials, and has been in clinical use for years for multiple sclerosis.
      Pegylated IFN formulations allow for weekly injections while maintaining serum levels and
      limiting dose-dependent side effects. Together these data support a sound safety profile for
      the planned intervention.

      The aim of this study is to ascertain whether IFN administered to index cases and household
      contacts of an index case, starting immediately following confirmed exposure (index case
      confirmed positive for SARS-CoV-2), will reduce duration of SARS-CoV-2 detectable by PCR in
      the index cases, and incidence of SARS-CoV-2 detectable by PCR in household contacts.
    

Detailed description: 
      Participants with COVID-19 will be identified from lists of patients with positive SARS-CoV-2
      PCR that is obtained daily from clinical laboratories, at COVID-19 outpatient and hospital
      clinics, or the Emergency Rooms in Chile. After telephonically pre-screening eligibility of
      the index case and his/her household, and participants providing informed consent, households
      will be randomized 1:1 to three doses of IFN beta 1a or standard of care. Only the index case
      and treatment-eligible household members will receive IFN if their household is assigned to
      treatment arm. Other non-eligible household participants (e.g. children) will be monitored by
      serial SARS-CoV-2 saliva PCR and diary cards, and at day 29 all participants will be
      evaluated for SARS-CoV-2 antibodies in blood.
    

Intervention name(s): Peginterferon beta-1a
Intervention type(s): Biological
Intervention description(s): Administration of trial drug: PLEGRIDY is given by an injection under the skin (subcutaneous injection). It will be administered to participants in accordance with product insert instructions by appropriately trained trial staff for whom administration of subcutaneous injections is within their normal scope of practice (e.g. RN or MD). They will wait for 20 mins after the last individual receives the interferon before leaving a residence. Administering staff will be supplied with appropriate PPE, trained in the use of this equipment and protocols for infection control, and will always attend in pairs.
PLEGRIDY will be administered in the home of the participants. Due to the heat-labile nature of the trial product (storage required at ~4oC) a verified English Spanish version of the product label will be printed by a GMP certified company and applied to the product and patient band just at the time of use.
Other intervention name(s): Plegridy
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A prospective, cluster randomised trial of interferon versus standard of care. Index cases will be identified from databases of positive COVID-19 PCR patients from the virology lab,('Fever') clinics, outpatient clinics and hospital emergency room visits for possible COVID-19. Household contacts will be identified via the index cases and will be approached with the consent of the index case.
Randomisation: Households will be randomised to receive IFN or standard of care (as recommended by the Public Health Department).
Trial population: Index cases positively infected with SARS-CoV-2 and their exposed household contacts. Index cases will be recruited from databases of individuals with confirmed COVID-19 identified from COVID-19 ('Fever') clinics and emergency room visits in Santiago, Chile.
Eligibility criteria: Households will be randomised only if cases and at least one treatment-eligible household contact meets all the inclusion criteria and none of the exclusion criteria.
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment