A Phase III Confirmatory Study of K-237

A Phase III Confirmatory Study of K-237-Multi-regional, Multi-center, Placebo Controlled, Randomized, Double Blind, Parallel Group Controlled Trial in Patients With Mild COVID-19

The efficacy and safety of K-237 0.3-0.4 mg/kg orally administered once daily for 3 days will be evaluated in patients with mild COVID-19 using a randomized, double-blind, parallel-group comparative method with placebo as a control. Efficacy will be assessed using a stratified log-rank test to determine the superiority of the drug over placebo in terms of time to improvement in clinical symptoms from the start of study drug administration to 168 hours.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: K-237 0.3-0.4mg/kg (once daily); Drug: Placebo 0.3-0.4mg/kg (once daily)

• Study Type: Interventional
• Enrollment (Actual): 1030
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 467-8602
    • Nagoya City University Hospital
  • Aichi, Japan, 453-0812
    • Hosokawa Surgical Clinic
  • Aichi, Japan, 462-8508
    • Nagoya City University West Medical Center
  • Aichi, Japan, 464-8547
    • Nagoya City University East Medical Center
  • Aichi, Japan, 466-0013
    • Naika Tonyobyonaika Maejima Iin
  • Aichi, Japan, 509-6134
    • Tohno Chuo Clinic
  • Chiba, Japan, 273-0121
    • Kamagaya General Hospital
  • Chiba, Japan, 273-8556
    • Japan Community Health care Organization Funabashi Central Hospital
  • Chiba, Japan, 286-8520
    • International University of Health and Welfare Narita Hospital
  • Fukuoka, Japan, 814-8525
    • Fukuoka Kinen Hospital
  • Fukuoka, Japan, 811-3195
    • National Hospital Organization Fukuokahigashi Medical Center
  • Gunma, Japan, 370-0829
    • National Hospital Organization Takasaki General Medical Center
  • Hiroshima, Japan, 734-8530
    • Hiroshima Prefectural Hospital
  • Hokkaido, Japan, 062-8618
    • Japan Community Health Care Organization Hokkaido Hospital
  • Ishikawa, Japan, 920-8650
    • National Hospital Organization Kanazawa Medical Center
  • Kagawa, Japan, 762-8550
    • Sakaide City Hospital
  • Kagoshima, Japan, 892-0822
    • Tenyoukai Central Hospital
  • Kanagawa, Japan, 252-0375
    • Kitasato University Hospital
  • Kanagawa, Japan, 210-0806
    • Kawasaki Rinko General Hospital
  • Kanagawa, Japan, 212-0024
    • Matsuba Clinic
  • Kanagawa, Japan, 220-0004
    • Maekawa Medical Clinic
  • Kanagawa, Japan, 224-0041
    • Tsuzuki Azuma Clinic Primary care and Rheumatology
  • Kanagawa, Japan, 232-0066
    • Mutsukawa Clinic Primary care and Gastroenterology
  • Kumamoto, Japan, 861-1196
    • NHO Kumamoto Saishun Medical Center
  • Kumamoto, Japan, 861-4173
    • Sakura Jyuji Hospital, Sakurajyuji Medical Corporation
  • Nagano, Japan, 381-2217
    • Minami Nagano Clinic
  • Nagasaki, Japan, 857-0134
    • Japan Organization of Occupational Health and Safety Nagasaki Rosai Hospital
  • Nara, Japan, 630-0213
    • Ikoma City Hospital
  • Niigata, Japan, 940-0861
    • Nagaoka Chuo General Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Okayama, Japan, 700-8557
    • Okayama City General Medical Center Okayama City Hospital
  • Osaka, Japan, 598-8577
    • Rinku General Medical Center
  • Osaka, Japan, 530-8480
    • Tazuke Kofukai Medical Research Institute, Kitano Hospital
  • Osaka, Japan, 552-0003
    • Japan Community Health care Organization Osaka Minato Central Hospital
  • Shiga, Japan, 525-8585
    • Omi Medical Center
  • Tochigi, Japan, 321-0114
    • Kuramochi Clinic Interpark
  • Tokyo, Japan, 193-0998
    • Tokyo Medical University Hachioji Medical Center
  • Tokyo, Japan, 153-0051
    • Mishuku Hospital
  • Tokyo, Japan, 103-0028
    • Tokyo Center Clinic
  • Tokyo, Japan, 108-0073
    • Tokyo Saiseikai Central Hospital
  • Tokyo, Japan, 108-8642
    • Kitasato University Kitasato Institute Hospital
  • Tokyo, Japan, 130-0012
    • Sumida General Clinic
  • Tokyo, Japan, 133-0052
    • Edogawa Hospital
  • Tokyo, Japan, 136-0072
    • Koto Hospital
  • Tokyo, Japan, 177-0051
    • Shimamura Memorial Hospital
  • Tokyo, Japan, 192-0918
    • Minamino Cardiovascular Hospital
  • Tokyo, Japan, 198-0042
    • Ome Municipal General Hospital
  • Toyama, Japan, 930-0194
    • Toyama University Hospital
  • Toyama, Japan, 937-0042
    • Japan Organization of Occupational Health and Safety Toyama Rosai Hospital
  • Toyama, Japan, 939-8511
    • Toyama City Hospital
  • Wakayama, Japan, 640-8505
    • Japan Organization of Occupational Health and Safety Wakayama Rosai Hospital
  • Wakayama, Japan, 646-8558
    • National Hospital Organization Minami Wakayama Medical Center
• Thailand
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital
  • Nonthaburi, Thailand, 11000
    • Bamrasnaradura Infectious Diseases Institute
  • Ratchaburi Provinc, Thailand, 70000
    • Ratchaburi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Persons who meet all of the following criteria will be eligible for this clinical trial.

1. Males and females who are 12 years of age or older at the time of obtaining consent
2. Those who are confirmed positive for SARS-CoV-2 by antigen test or RT-PCR test using specimens (nasopharynx, nasal cavity, oropharynx, or saliva) collected within 120 hours prior to obtaining consent.
3. Patients who have fevers (37.5 degrees Celsius or higher) and/or at least one of the following symptoms of Score 2 or higher at a screening test: Myalgia, sore throat, diarrhea, nausea, vomiting, cough, and shortness of breath.
4. Patients with a room air oxygen saturation (SpO2) of 96% or higher at the time of the screening test.

Exclusion Criteria:

• Subjects who meet any one of the following criteria will be excluded from this study.

  1. Patients who have had symptoms caused by COVID-19 for more than 6 days on the day of initiation of study drug administration (Day 1) with the day of onset of symptoms as Day 0.
  2. Patients who need to receive concomitant therapy or administration of prohibited drugs during the study period
  3. Patients who have taken or received drugs that have or may have antiviral activity against SARS-CoV-2 within 2 weeks prior to the start of study drug administration.
  4. Patients currently using antiviral drugs
  5. Patients with suspected complications of infectious diseases other than COVID-19
  6. Subjects with a history of COVID-19 within 1 month prior to obtaining consent
  7. Persons whose weight at the time of the screening test falls into the following categories (The first decimal place of the weight shall be rounded off.) 1) Those who are 18 years of age or older at the time of consent and weigh less than 25 kg or more than 127 kg 2) Those who are between 12 and 18 years of age and weigh less than 40 kg or 127 kg or more at the time of obtaining consent.
  8. Patients undergoing dialysis treatment
  9. Patients wno have severe liver dysfunction (hepatic dysfunction, hepatic fibrosis, etc.)
  10. Patients with poorly controlled hypertension (systolic blood pressure (SBP) of 180 mmHg or higher or diastolic blood pressure (DBP) of 110 mmHg or higher)
  11. Patients with complications of diabetic retinopathy, diabetic nephropathy, or diabetic neuropathy
  12. Patients with heart failure of NYHA Class III or higher
  13. Patients with malignant tumors or those judged to have a high possibility of recurrence
  14. Patients requiring oxygen therapy
  15. A person who has a complication of methemoglobinemia or any other disease that may cause measurement error of the pulse oximeter
  16. Patients with a history of serious drug allergy (anaphylactic shock, etc.)
  17. Pregnant women, lactating women, or women who plan to become pregnant or lactate during the study period
  18. Subjects who have had more than 400 mL of whole blood drawn within 16 weeks or more than 200 mL within 4 weeks prior to obtaining consent, or component blood (plasma and platelet components) drawn within 2 weeks
  19. Patients who have been administered IVM.
  20. Those who have participated in other clinical trials and received medication at the time of obtaining consent, or those who have received an investigational drug other than placebo for less than 16 weeks
  21. Others who are judged by the investigator or others to be inappropriate to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; K-237 0.3-0.4mg/kg (once daily)	Drug: K-237 0.3-0.4mg/kg (once daily); Ivermectin 3mg tablet; Other Names: Ivermectin 0.3-0.4mg/kg (once daily)
Placebo Comparator: Control A; Placebo (once daily)	Drug: Placebo 0.3-0.4mg/kg (once daily); Placebo 3mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time from the start of study drug administration to 168 hours until the clinical symptoms reach an improving trend	Day1～11 after administration

Secondary Outcome Measures

Outcome Measure	Time Frame
In addition to the primary endpoint, time to trend toward improvement in clinical symptoms, including headache, abdominal pain, nasal	Day1～11 after administration
Time to reach a temperature of less than 37.5 ˚C without the use of antipyretics (acetaminophen)	Day1～11 after administration

Collaborators and Investigators

• Sponsor: Kowa Company, Ltd.

Publications and helpful links

General Publications

• Mikamo H, Takahashi S, Yamagishi Y, Hirakawa A, Harada T, Nagashima H, Noguchi C, Masuko K, Maekawa H, Kashii T, Ohbayashi H, Hosokawa S, Maejima K, Yamato M, Manosuthi W, Paiboonpol S, Suganami H, Tanigawa R, Kawamura H; IVERMILCO Study Group. Efficacy and safety of ivermectin in patients with mild COVID-19 in Japan and Thailand. J Infect Chemother. 2024 Jun;30(6):536-543. doi: 10.1016/j.jiac.2023.12.012. Epub 2023 Dec 27.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Actual): August 26, 2022
• Study Completion (Actual): August 26, 2022

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (Actual): September 27, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiparasitic Agents; Ivermectin
• Other Study ID Numbers: K-237-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No