Safety of TY027, a Treatment for COVID-19, in Humans

NCT04429529 | Completed Phase 1 DMC

• 1 other identifier: SCT-001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Coronavirus Disease-2019 (COVID-19)

Keywords

Coronavirus Disease-2019; COVID-19; SARS-CoV-2; Monoclonal Antibody; Infectious diseases; Phase 1 first in human study; Singapore

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  To assess the safety and tolerability of an intravenous (IV) infusion of TY027 when administered to healthy adult volunteers. This will be assessed at various time points by clinical laboratory tests, vital signs and adverse events

  84 Days

Secondary Outcomes (7)

• Maximum Concentration (Cmax) - Pharmacokinetic Assessment

  84 Days

• Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment

  84 Days

• Area Under the Curve Extrapolated to Infinity (AUC0-∞) - Pharmacokinetic Assessment

  84 Days

• AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment

  84 Days

• Half-Life (t1/2) - Pharmacokinetic Assessment

  84 Days

Study Arms (10)

TY027 0.5 mg/kg

EXPERIMENTAL

Subject will be administered with 0.5 mg/kg of TY027 via IV infusion over a period of 30 minutes.

Biological: TY027

Placebo 0.5 mg/kg

PLACEBO COMPARATOR

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Other: 0.9% Saline

TY027 5mg/kg

EXPERIMENTAL

Subject will be administered with 5 mg/kg of TY027 via IV infusion over a period of 30 minutes.

Biological: TY027

Placebo 5 mg/kg

PLACEBO COMPARATOR

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Other: 0.9% Saline

TY027 10 mg/kg

EXPERIMENTAL

Subject will be administered with 10 mg/kg of TY027 via IV infusion over a period of 30 minutes.

Biological: TY027

Placebo 10 mg/kg

PLACEBO COMPARATOR

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Other: 0.9% Saline

TY027 20 mg/kg

EXPERIMENTAL

Subject will be administered with 20 mg/kg of TY027 via IV infusion over a period of 30 minutes.

Biological: TY027

Placebo 20 mg/kg

PLACEBO COMPARATOR

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Other: 0.9% Saline

TY027 30 mg/kg

EXPERIMENTAL

Subject will be administered with 30 mg/kg of TY027 via IV infusion over a period of 30 minutes.

Biological: TY027

Placebo 30 mg/kg

PLACEBO COMPARATOR

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Other: 0.9% Saline

Interventions

TY027 BIOLOGICAL

TY027 Injection, (100 mg/5 mL/Vial), SARS-CoV-2 Monoclonal Antibody (mAb)

TY027 0.5 mg/kg; TY027 10 mg/kg; TY027 20 mg/kg; TY027 30 mg/kg; TY027 5mg/kg

0.9% Saline OTHER

Placebo

Placebo 0.5 mg/kg; Placebo 10 mg/kg; Placebo 20 mg/kg; Placebo 30 mg/kg; Placebo 5 mg/kg

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult volunteers, aged 21 to 50 years old, men or women
• Subjects negative for human immunodeficiency virus (HIV antibody screen), Hepatitis B virus surface Antigen (HBsAg) and Hepatitis C virus (HCV antibody screen)
• Subjects who are willing to comply with the requirements of the study protocol, attend scheduled visits and make themselves available for the duration of the study with access to a consistent means of telephone contact, which may be, but not limited to, at home or at work via landline or mobile
• Subjects who give written informed consent approved by the Ethical Review Board governing the site
• Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. Normal laboratory values must be within normal range of the assessing site or show minor variations that are deemed not clinically significant as judged by the Investigator and acceptable for study entry. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event
• Accessible vein in the forearm for blood collection
• Female subjects of childbearing potential may be enrolled in the study if they have negative urine pregnancy tests on the day of screening and day of admission
• Female subjects of non-childbearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Post- menopause subjects must have had at least 12 months of natural (spontaneous) amenorrhea
• Both male (if he has a partner of childbearing potential) and female subjects (of childbearing potential) must agree to use adequate and reliable contraceptive measures (e.g. spermicides, condoms, contraceptive pills, etc.) or practice abstinence throughout the duration of the study (up to 84 days post-dosing)

You may not qualify if:

• Subject previously diagnosed with COVID-19 or had been issued with a quarantine order by the Ministry of Health
• Presence of acute infection in the preceding 14 days, or presence of a temperature ≥ 38.0 ˚C (oral or tympanic temperature assessment), or acute symptoms of any severity on the scheduled date of admission
• History of severe drug and / or food allergies and / or known allergies to the trial product or its components
• Female subject who is pregnant or breast-feeding
• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, or immunosuppressive disorders
• Evidence of clinically significant anaemia (HB \< 10 g/dL) or any other significant active haematological disease, or having donated \> 450 mL of blood within the past three (3) months
• Participation or planned participation in a study involving the administration of an investigational compound within the past four (4) months or during this study period
• Receipt of immunoglobulins and/or any blood products within nine (9) months of study enrolment or planned administration of any of these products during the study period
• Administration of any licensed vaccine within 30 days before the first study vaccine dose.
• History of any reaction to monoclonal antibodies
• Any condition that, in the opinion of the Investigator, would complicate or compromise the study or well-being of the subject
• Both male (if he has a partner of childbearing potential) and female subjects (of childbearing potential) who are unwilling to use adequate contraception or practice abstinence throughout the duration of the study (up to 84 days post-dosing)

Sponsors & Collaborators

• Tychan Pte Ltd.: lead

Study Sites (1)

SingHealth Investigational Medicine Unit

Singapore, 169608, Singapore

Location

Related Publications (1)

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19; Communicable Diseases

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jenny Low, MBBS

  SingHealth Investigational Medicine Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are assigned to either treatment or placebo

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 12, 2020
• Study Start: June 9, 2020
• Primary Completion: November 19, 2020
• Study Completion: January 20, 2021
• Last Updated: April 8, 2021

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)