Safety of TY027, a Treatment for COVID-19, in Humans
Condition: Coronavirus Disease-2019 (COVID-19)
MeSH terms: COVID-19; Coronavirus Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The emergence and rapid spread of the coronavirus disease 2019 (COVID-19) since December 2019
      across 188 countries globally has become a major public health crisis. COVID-19 was declared
      a pandemic by the World Health Organisation (WHO) on the 11th March 2020. To date, more than
      14,000,000 cases and 600,000 deaths have been reported. COVID-19 is an acute respiratory
      disease caused by the novel SARS-CoV-2 virus from the Betacoronavirus genus, just like
      SARS-CoV and MERS-CoV. SARS-CoV-2 is primarily transmitted person-to-person through
      respiratory droplets or close contact. Fomite transmission has also been implicated as a
      transmission route. Common respiratory symptoms such as fever, sore throat, cough and
      shortness of breath, may appear 2 - 14 days after exposure. About 20% of infected cases
      progress to severe disease resulting in an estimated 2 - 5% mortality reported. With the
      unrelenting increase in cases being reported worldwide, there is thus an urgent need for
      therapeutics to be developed and used to disrupt the ongoing pandemic.

      To date, there is no specific proven antiviral treatment for COVID-19. Supportive care is
      recommended for symptom relief and for severe cases, organ support is critical for optimal
      outcome. Numerous vaccine candidates against SARS-CoV-2 are under development and a couple
      have entered Phase 1 clinical trials. Remdesivir, a nucleotide analog, developed by Gilead
      Sciences as a treatment for Ebola virus disease is currently being repurposed and undergoing
      multiple clinical trials to evaluate safety and efficacy in COVID-19 patients. In a
      preliminary study, convalescent plasma containing neutralizing antibodies against SARS-CoV-2
      has also been experimentally administered in critically ill COVID-19 patients with promising
      results. Donor plasma used was rich in virus specific IgG and IgM antibodies as determined by
      ELISA. Within days of convalescent plasma treatment, patients showed decrease in viral load
      (via qRT-PCR), as well as improved clinical status being observed. Tychan's TY027 will be the
      first biologics in the world, specifically targeting SARS-CoV-2, to enter human clinical
      trials. It is anticipated that a SARS-COV-2 specific monoclonal antibody therapeutic
      administered to acutely infected patients could reduce disease severity as well as prevent
      transmission by reducing viral load and viral shedding. It could also be used as prophylaxis
      against COVID-19 amongst high risk contacts.
    

Detailed description: 
      This is a Phase 1 First-in-Human, Time Lagged, Randomised, Placebo Controlled, Double Blind,
      Single Ascending Dose Study of TY027 in Healthy Adult Volunteers.

      Safety, tolerability and PK of TY027 will be assessed. The dose escalation will include 32
      healthy volunteers across five (5) dose cohorts:

        -  0.5 mg/kg, N = 2 TY027 + 2 Placebos

        -  5 mg/kg, N = 5 TY027 + 2 Placebos

        -  10 mg/kg, N = 5 TY027 + 2 Placebos

        -  20 mg/kg, N = 5 TY027 + 2 Placebos

        -  30 mg/kg, N = 5 TY027 + 2 Placebos

      Subjects will be required to be inpatient at the trial site for approximately 24 hours.

      A minimum of 20-hour interval from the first two (2) subjects dosing (1 treatment and 1
      placebo concurrently) must take place before the third subject can be dosed within the
      cohort. No such time interval will be required for dosing of subsequent subjects (fourth
      subject onwards) within the same dose cohort.

      After 24 hours, subjects will be discharged from the trial site and to return for scheduled
      follow-up visits. Subjects will be followed for up to approximately Day 84 with serum samples
      taken at specified times as per outlines in Table 1.

      Dose escalations will be guided by a safety review of clinical signs, adverse events (AEs),
      laboratory tests (excluding lipase) and immune gene expression data of the prior dose cohort
      (up to 72 hours post-dose). Subsequent post-trial monitoring through weekly telephone calls
      will continue from Day 85 onwards for another three (3) more months.

      Decisions not to dose escalate past any proposed dose level due to safety findings will not
      constitute a protocol violation.

      Safety summaries (up to Day 3 post-dose) will be generated for each dose cohort and delivered
      to the Dose Escalation Review Committee (DERC) for review.

      Interim analysis will be performed after Day 14 post-dose for each dose cohort and delivered
      to the Data Safety Monitoring Board (DSMB) for review.
    

Intervention name(s): TY027; 0.9% Saline
Intervention type(s): Biological; Other
Intervention description(s): TY027 Injection, (100 mg/5 mL/Vial), SARS-CoV-2 Monoclonal Antibody (mAb); Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants are assigned to either treatment or placebo
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Coronavirus Disease-2019; COVID-19; SARS-CoV-2; Monoclonal Antibody; Infectious diseases; Phase 1 first in human study; Singapore