Safety and Efficacy Study of STI-1558 in Healthy Adults and SARS-CoV-2-Positive Patients

NCT05523739 | Completed Phase 1

• 1 other identifier: MPR-COV-101CN
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety of STI-1558 in healthy subjects and the safety, pharmacokinetics, and efficacy in SARS-CoV-2-Positive subjects.

Conditions

SARS-CoV-2 Infection

Outcome Measures

Primary Outcomes (1)

• AE, laboratory tests, thyroid function, physical examination, vital signs.

  Incidence and severity of AEs up to 6 days for part 1 and 21 days for part 2 post-dosing.

  Day 7 for part 1 and day 29 for part 2.

Secondary Outcomes (6)

• Proportion of changes from baseline in SARS-CoV-2 RNA quantification levels on D3, D5, D7, D10, D14, D21, D29.

  Day3, Day5, Day7, Day10, Day14, Day21, Day29

• Proportion of SARS-CoV-2 RNA quantification levels below the lower limit of quantification on D3, D5, D7, D10, D14, D21, D29.

  Day3, Day5, Day7, Day10, Day14, Day21, Day29.

• Pharmacokinetic parameter of AUC

  Day1, Day2, Day3 for part 1 and Day1, Day6, Day7, Day8 for part 2

• Pharmacokinetic parameter of Cmax

  Day1, Day2, Day3 for part 1 and Day1, Day6, Day7, Day8 for part 2

• Pharmacokinetic parameter of Tmax

  Day1, Day2, Day3 for part 1 and Day1, Day6, Day7, Day8 for part 2

Study Arms (7)

Part 1: Cohort 1

EXPERIMENTAL

Participants will receive a single 300 mg dose of STI-1558 or placebo. Cohort 1 will dose 6 subjects to STI-1558 and 2 subjects to placebo.

Drug: STI-1558

Part 1: Cohort 2

EXPERIMENTAL

Participants will receive a single 600 mg dose of STI-1558 or placebo. Cohort 2 will dose 6 subjects to STI-1558 and 2 subjects to placebo.

Drug: STI-1558

Part 1: Cohort 3

EXPERIMENTAL

Participants will receive a single 1200 mg dose of STI-1558 or placebo. Cohort 3 will dose 6 subjects to STI-1558 and 2 subjects to placebo.

Drug: STI-1558

Part 1: Cohort 4

EXPERIMENTAL

Participants will receive a single 2000 mg dose of STI-1558 or placebo. Cohort 4 will dose 6 subjects to STI-1558 and 2 subjects to placebo.

Drug: STI-1558

Part 2: Cohort 1

EXPERIMENTAL

Participants will receive a 300 mg dose of STI-1558 or placebo q12h on Day1 to Day7 and once in the morning on Day8 for a total of 15 doses. Cohort 1 will dose 6 subjects to STI-1558 and 2 subjects to placebo.

Drug: STI-1558

Part 2: Cohort 2

EXPERIMENTAL

Participants will receive a 600 mg dose of STI-1558 or placebo q12h on Day1 to Day7 and once in the morning on Day8 for a total of 15 doses. Cohort 2 will dose 16 subjects to STI-1558 and 8 subjects to placebo.

Drug: STI-1558

Part 2: Cohort 3

EXPERIMENTAL

Participants will receive a 800 mg dose of STI-1558 or placebo q12h on Day1 to Day7 and once in the morning on Day8 for a total of 15 doses. Cohort 3 will dose 16 subjects to STI-1558 and 8 subjects to placebo.

Drug: STI-1558

Interventions

STI-1558 DRUG

An oral small molecule prodrug that effectively inhibits the SARS-CoV-2 main protease (Mpro).

Part 1: Cohort 1; Part 1: Cohort 2; Part 1: Cohort 3; Part 1: Cohort 4; Part 2: Cohort 1; Part 2: Cohort 2; Part 2: Cohort 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1
• Subjects are fully informed of the study and sign the informed consent document prior to any procedure.
• Healthy subjects aged ≥18 but ≤45 years old, regardless of gender.
• BMI ≥18, but ≤30kg/m2, and weight ≥45, but ≤100kg.
• Good health status, with normal or abnormal and not clinically significant (NCS) results of medical history, vital signs, physical examination, 12-lead electrocardiogram, laboratory tests (blood routine, blood chemistry, urine routine, coagulation function) and thyroid function (TSH, FT3, FT4) during the screening period.
• Must be willing and able to comply with all planned study procedures.
• Women of childbearing potential (WOCBP) (infertile women defined as having undergone hysterectomy or bilateral oophorectomy or bilateral salpingectomy or bilateral tubal ligation/closure, or who are infertile due to a congenital or acquired condition or spontaneously menopausal for ≥ 12 months) must have a negative blood pregnancy test during screening. Fertility female and male subjects must use a highly effective method of contraception from the screening period to 90 days after the last dose of study drug.
• Part 2
• Subjects are fully informed of the study and sign the informed consent document prior to any procedure.
• Age ≥ 18, but \< 65 years old, gregardless of gender.
• BMI ≥18, but ≤30kg/m2, and weight ≥45, but ≤100kg.
• Asymptomatic or mild patients diagnosed with SARS-CoV-2 positive according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 9).
• First positive for SARS-CoV-2 in specimens such as nasal or oropharyngeal swabs within 5 days prior to D1 (≤5 days from D1) using nucleic acid amplification assays.
• Requirements for laboratory test values, including:
• Alanine aminotransferase (AST) ≤ 2.5×ULN

You may not qualify if:

• Subjects who faint with needles, faint with blood, or have difficulty collecting venous blood.
• Known hypersensitivity to any of the ingredients of this product.
• Participated in an interventional clinical trial within 30 days before D1 or within 5 half-lives (whichever is longer).
• Subjects who have a history of gastrointestinal (such as duodenal ulcer, gastrointestinal bleeding), liver or kidney-related medical history, or other medical history that may affect the absorption, distribution, metabolism, and excretion of oral drugs as assessed by the investigator.
• Subjects who have undergone major surgery within 3 months prior to screening, or who have not fully recovered from surgery, or who plan to undergo surgery during the study period.
• Take foods, juices or beverages containing alcohol, grapefruit, lime, cinchona bark and quinine within 24 hours prior to D1.
• Use of BCRP substrate drugs within 7 days prior to D1 (see "6.5.1 Prohibited Drugs and Treatments").
• History of substance abuse within 2 years prior to screening.
• Subjects who have donated blood (including blood components donation) or lost more than 400 mL of blood within 3 months prior to screening.
• History of alcohol abuse (defined as: more than 14 units of alcohol per week, 1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of spirit containing 40% alcohol) within 3 months prior to screening.
• Refusal to abstain from smoking after signing the informed consent form and during the study.
• Excessive consumption of tea, coffee or caffeinated beverages (defined as: at least 8 cups per day, 1 cup = 250 ml) within 3 months prior to screening.
• Currently pregnant or breastfeeding.
• According to the investigator's judgment, the subject has any other disease or condition that may affect the normal completion of the study or the evaluation of the study data, or other conditions that are not suitable for participation in this study.
• Healthy subjects are not allowed to join the part 1 if they meet any of the following criteria:

Sponsors & Collaborators

• Zhejiang ACEA Pharmaceutical Co. Ltd.: lead

Study Sites (1)

The Third People's Hospital Of Shenzhen

Shenzhen, Guangdong, China

Location

Related Publications (1)

• Mao L, Shaabani N, Zhang X, Jin C, Xu W, Argent C, Kushnareva Y, Powers C, Stegman K, Liu J, Xie H, Xu C, Bao Y, Xu L, Zhang Y, Yang H, Qian S, Hu Y, Shao J, Zhang C, Li T, Li Y, Liu N, Lin Z, Wang S, Wang C, Shen W, Lin Y, Shu D, Zhu Z, Kotoi O, Kerwin L, Han Q, Chumakova L, Teijaro J, Royal M, Brunswick M, Allen R, Ji H, Lu H, Xu X. Olgotrelvir, a dual inhibitor of SARS-CoV-2 Mpro and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19. Med. 2024 Jan 12;5(1):42-61.e23. doi: 10.1016/j.medj.2023.12.004. Epub 2024 Jan 4.

  PMID: 38181791 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

STI-1558

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

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

Study Record Dates

• First Submitted: August 25, 2022
• First Posted: August 31, 2022
• Study Start: September 16, 2022
• Primary Completion: December 21, 2022
• Study Completion: March 29, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)