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

NCT04649515 | Terminated Phase 3 DMC

• 1 other identifier: SCT-301
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The emergence \& 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 on 11 March 2020. To date, tens of millions of cases have been reported and over 3% of these cases have died. 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/close contact. Fomite transmission has also been shown as a transmission route. Common respiratory symptoms such as fever, sore throat, cough \& 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 rate. With the unrelenting increase in cases being reported worldwide, there is thus an urgent need for therapeutics to be developed to treat disease \& reduce further transmission in order to disrupt the ongoing pandemic. To date, there are no specific proven antiviral treatment to prevent disease progression from mild to severe respiratory dysfunction among COVID-19 patients. Supportive care is recommended for symptom relief \& for severe cases. Numerous vaccine candidates against SARS-CoV-2 are under development. Tychan's TY027, a fully engineered human IgG, is one of the first few biologics in the world, specifically targeting SARS-CoV-2, to enter human clinical trials. Preliminary data from our phase 1 healthy volunteer trial (SCT-001; ClinicalTrials.gov Identifier NCT04429529) reveals that TY027 is safe \& well-tolerated up to 20 mg/kg tested. A total of 10 adverse events (AEs) were observed, all were of mild in intensity with none resulting in subject withdrawal from the study. There were no serious adverse events \& no clinically relevant trends in mean clinical laboratory, physical examinations, vital signs or ECG results were observed. Pharmacokinetic profile of subjects across dose cohorts 1 - 4, up to Day 14, were comparable to those typical of human IgG1 antibody with serum concentrations declining in a biphasic manner. Exposure of TY027, based on Cmax, increased in a linear \& generally dose proportional manner. It is anticipated that TY027, when administered to acutely infected COVID-19 patients, could reduce disease severity. It may potentially also be used as a 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 3 study; Singapore

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of a single dose intravenous (IV) infusion of TY027 in reducing disease progression, defined as progression to score 4 and below on COVID scale

  Proportion of COVID-19 patients with disease progression, defined as progression to score 4 and below on the COVID Scale, within the first 14 days after a single dose IV infusion of TY027 as compared to placebo

  Within the first 14 days

Secondary Outcomes (6)

• Rate of AEs (grade 3 and above) and SAEs in COVID-19 patients

  28 days

• All cause mortality rate

  28 days

• Proportion of subjects in categories 4, 3, 2 and 1 of the COVID scale

  Up to Day 28

• Number of days COVID-19 patients require supplemental oxygen, high flow oxygen, non-invasive and invasive mechanical ventilation (if applicable)

  28 days

• Proportion of COVID-19 patients tested negative for SARS-CoV-2 via reverse transcriptase-polymerase chain reaction (RT-PCR)

  Up to Day 28

Study Arms (3)

TY027 1,500 mg

EXPERIMENTAL

1,500 mg of TY027 will be administered via IV infusion over a period of 30 minutes.

Biological: TY027

TY027 2,000 mg

EXPERIMENTAL

2,000 mg of TY027 will be administered via IV infusion over a period of 30 minutes.

Biological: TY027

Placebo

PLACEBO COMPARATOR

Placebo will be administered 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) - 1,500 mg of TY027

TY027 1,500 mg

0.9% saline OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic and RT-PCR confirmed COVID-19 within 6 days from symptom onset.
• Has any one of the following factors associated with disease progression:
• Elevated lactate dehydrogenase (LDH)
• Elevated C reactive protein (CRP)
• Lymphocyte count below normal limit
• Age 40 and above
• History of well-controlled diabetes, hypertension, chronic obstructive lung disease or ischemic heart diseases
• Stable chronic renal disease
• History of asthma
• Disease outcome score of 6, 7 or 8 based on the COVID Scale
• Willing to comply with the requirements of the study protocol and attend scheduled study visits
• Can give written informed consent approved by the Ethical Review Board governing the site

You may not qualify if:

• Aged below 21 years old
• Female who is pregnant or breast-feeding
• With the following conditions, but not limited to:
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy defined as prednisone or equivalent for more than 2 consecutive weeks within the past 3 months
• Child-Pugh Class C chronic liver disease
• Renal insufficiency with an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2 calculated by the CKD-EPI formula
• Suspected or confirmed active bacterial, fungal or mycobacterial infection
• History of any allergic reaction to monoclonal antibodies
• Currently enrolled in another COVID-19 investigational drug study
• Previously enrolled in a COVID-19 investigational vaccine study
• Any medical condition, which in the opinion of the Investigator, will compromise the safety of the patient

Sponsors & Collaborators

• Tychan Pte Ltd.: lead

Study Sites (1)

Singapore General Hospital

Singapore, 169856, 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

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: November 26, 2020
• First Posted: December 2, 2020
• Study Start: December 4, 2020
• Primary Completion: March 4, 2022
• Study Completion: March 4, 2022
• Last Updated: March 24, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)