Clinical trial NCT05056883: A Phase III Confirmatory Study of K-237
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Covid19
Lead sponsor: Kowa Company, Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-27
Enrollment: 1030
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time from the start of study drug administration to 168 hours until the clinical symptoms reach an improving trend
timeFrame: Day1～11 after administration
Secondary outcomes:
measure: In addition to the primary endpoint, time to trend toward improvement in clinical symptoms, including headache, abdominal pain, nasal
timeFrame: Day1～11 after administration
measure: Time to reach a temperature of less than 37.5 ˚C without the use of antipyretics (acetaminophen)
timeFrame: Day1～11 after administration
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Hosokawa Surgical Clinic
city: Aichi
country: Japan
facility: Nagoya City University West Medical Center
city: Aichi
country: Japan
facility: Nagoya City University East Medical Center
city: Aichi
country: Japan
facility: Naika Tonyobyonaika Maejima Iin
city: Aichi
country: Japan
facility: Nagoya City University Hospital
city: Aichi
country: Japan
facility: Tohno Chuo Clinic
city: Chiba
country: Japan
facility: Kamagaya General Hospital
city: Chiba
country: Japan
facility: Japan Community Health care Organization Funabashi Central Hospital
city: Chiba
country: Japan
facility: International University of Health and Welfare Narita Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Fukuokahigashi Medical Center
city: Fukuoka
country: Japan
facility: Fukuoka Kinen Hospital
city: Gunma
country: Japan
facility: National Hospital Organization Takasaki General Medical Center
city: Hiroshima
country: Japan
facility: Hiroshima Prefectural Hospital
city: Hokkaido
country: Japan
facility: Japan Community Health care Organization Hokkaido Hospital
city: Ishikawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
city: Kagawa
country: Japan
facility: Sakaide City Hospital
city: Kagoshima
country: Japan
facility: Tenyoukai Central Hospital
city: Kanagawa
country: Japan
facility: Kawasaki Rinko General Hospital
city: Kanagawa
country: Japan
facility: Matsuba Clinic
city: Kanagawa
country: Japan
facility: Maekawa Medical Clinic
city: Kanagawa
country: Japan
facility: Tsuzuki Azuma Clinic Primary care and Rheumatology
city: Kanagawa
country: Japan
facility: Mutsukawa Clinic Primary care and Gastroenterology
city: Kanagawa
country: Japan
facility: Kitasato University Hospital
city: Kumamoto
country: Japan
facility: NHO Kumamoto Saishun Medical Center
city: Kumamoto
country: Japan
facility: Sakura Jyuji Hospital, Sakurajyuji Medical Corporation
city: Nagano
country: Japan
facility: Minami Nagano Clinic
city: Nagasaki
country: Japan
facility: Japan Organization of Occupational Health and Safety Nagasaki Rosai Hospital
city: Nara
country: Japan
facility: Ikoma City Hospital
city: Niigata
country: Japan
facility: Nagaoka Chuo General Hospital
city: Okayama
country: Japan
facility: Okayama City General Medical Center Okayama City Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Tazuke Kofukai Medical Research Institute, Kitano Hospital
city: Osaka
country: Japan
facility: Japan Community Health care Organization Osaka Minato Central Hospital
city: Osaka
country: Japan
facility: Rinku General Medical Center
city: Shiga
country: Japan
facility: Omi Medical Center
city: Tochigi
country: Japan
facility: Kuramochi Clinic Interpark
city: Tokyo
country: Japan
facility: Tokyo center clinic
city: Tokyo
country: Japan
facility: Tokyo Saiseikai Central Hospital
city: Tokyo
country: Japan
facility: Kitasato University Kitasato Institute Hospital
city: Tokyo
country: Japan
facility: Sumida General Clinic
city: Tokyo
country: Japan
facility: Edogawa Hospital
city: Tokyo
country: Japan
facility: Koto Hospital
city: Tokyo
country: Japan
facility: Mishuku Hospital
city: Tokyo
country: Japan
facility: Shimamura Memorial Hospital
city: Tokyo
country: Japan
facility: Minamino Cardiovascular Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical University Hachioji Medical Center
city: Tokyo
country: Japan
facility: Ome Municipal General Hospital
city: Toyama
country: Japan
facility: Toyama University Hospital
city: Toyama
country: Japan
facility: Japan Organization of Occupational Health and Safety Toyama Rosai Hospital
city: Toyama
country: Japan
facility: Toyama City Hospital
city: Wakayama
country: Japan
facility: Japan Organization of Occupational Health and Safety Wakayama Rosai Hospital
city: Wakayama
country: Japan
facility: National Hospital Organization Minami Wakayama Medical Center
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Infectious Diseases Institute
city: Ratchaburi Provinc
country: Thailand
facility: Ratchaburi Hospital
Study officials:
References:
citation: 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.