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Trial registered on ANZCTR


Registration number
ACTRN12623000035628
Ethics application status
Approved
Date submitted
5/01/2023
Date registered
13/01/2023
Date last updated
3/05/2023
Date data sharing statement initially provided
13/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of the safety and efficacy of 7 days treatment with BIT225 in patients with COVID-19, compared to placebo, including measurement of antiviral activity, clinical recovery and immune biomarkers.
Scientific title
A Phase 2, Double Blind Placebo-Controlled Study of BIT225, an Orally Administered SARS-CoV-2 Viroporin Inhibitor, to Evaluate Antiviral Activity, Safety, and Immune Biomarkers in Non-Hospitalised Vaccinated and Unvaccinated Adults with COVID-19.
Secondary ID [1] 308688 0
BIT225-012
Universal Trial Number (UTN)
U1111-1286-7528
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 328623 0
Condition category
Condition code
Infection 325626 325626 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Screening, enrolment, treatment randomisation and first dosing will occur on Screening / Day 1
Arm 1-BIT225 200mg (1 x 100mg capsule) twice daily (BID), oral, from Day 1 to Day 7
Arm 2-BIT225 400mg (2 x 100mg capsule) twice daily (BID), oral, from Day 1 to Day 7
Capsule counts on return will be used to monitor adherence.
Intervention code [1] 325156 0
Treatment: Drugs
Comparator / control treatment
Placebo control, capsules containing microcrystalline cellulose, taken twice daily (BID), oral, from Day 1 to Day 7.
Capsule counts on return will be used to monitor adherence.
Control group
Placebo

Outcomes
Primary outcome [1] 333472 0
To determine the safety and tolerability of BIT225 when dosed at 200mg or 400 mg per day, or matching placebo administered for 7 consecutive days in individuals newly diagnosed with SARS-CoV-2 within 3 days of the first onset of symptoms. Safety and tolerability will be assessed by comparison to placebo of treatment emergent untoward medical changes, e.g. changes in clinical laboratory assessments (hematology, coagulation, biochemistry), vital signs (temperature assessed by thermometer, respiratory and pulse rate assessed as a manual count) and ECG measures.
Timepoint [1] 333472 0
Medical changes and vital signs will be evaluated at Screening, Days 3, 5, and 7 and follow-up Days 10 and 21 post-intervention commencement.
Clinical Laboratory measures will be evaluated at Screening and Day 7 and follow-up Day 21 post-intervention commencement.
ECG measurements will be evaluated at Screening, Days 5 and 7, and follow-up Days 10 and 21 post-intervention commencement.
Primary outcome [2] 333476 0
To determine the efficacy of BIT225 when dosed at 200 mg, 400 mg per day, or matching placebo administered for 7 consecutive days in individuals diagnosed with SARS-CoV-2 within 3 days of the onset of symptoms, based on SARS-CoV-2 nasal viral load, including kinetics of change and time to negative SARS-CoV-2 PCR. This will be assessed as a composite outcome.
Timepoint [2] 333476 0
SARS-CoV-2 test (nasal swab) will be collected each day up to Day 10 and follow-up Day 21 post-intervention commencement. Samples to be analysed by RT-PCR.
Secondary outcome [1] 417206 0
To determine the efficacy of BIT225 when dosed at 200 mg, 400 mg per day, or matching placebo administered for 7 consecutive days in individuals diagnosed with SARS-CoV-2 within 3 days of the onset of symptoms, based on multiple clinical outcome measures including time to sustained clinical recovery.
Timepoint [1] 417206 0
COVID-19 symptoms will be captured daily and graded through use of a participant diary.
Secondary outcome [2] 417207 0
To determine the efficacy of BIT225 when dosed at 200 mg, 400 mg per day, or matching placebo administered for 7 consecutive days in individuals diagnosed with SARS-CoV-2 within 3 days of the onset of symptoms, based on multiple clinical outcome measures including: time to clinical improvement.
Timepoint [2] 417207 0
COVID-19 symptoms will be captured daily and graded through use of a participant diary.
Secondary outcome [3] 417284 0
To determine the efficacy of BIT225 when dosed at 200 mg, 400 mg per day, or matching placebo administered for 7 consecutive days in individuals diagnosed with SARS-CoV-2 within 3 days of the onset of symptoms, based on multiple clinical outcome measures including rate of hospitalisation.
Timepoint [3] 417284 0
Adverse events will be monitored throughout the study and assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTAE). COVID-19 symptoms will be captured daily and graded through use of a participant diary.
Secondary outcome [4] 417285 0
To determine the efficacy of BIT225 when dosed at 200 mg, 400 mg per day, or matching placebo administered for 7 consecutive days in individuals diagnosed with SARS-CoV-2 within 3 days of the onset of symptoms, based on multiple clinical outcome measures including rate of all-cause mortality.
Timepoint [4] 417285 0
Adverse events will be monitored throughout the study and assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTAE). COVID-19 symptoms will be captured daily and graded through use of a participant diary.
Secondary outcome [5] 417286 0
To determine the efficacy of BIT225 when dosed at 200 mg, 400 mg per day, or matching placebo administered for 7 consecutive days in individuals diagnosed with SARS-CoV-2 within 3 days of the onset of symptoms, based on multiple clinical outcome measures including rate of recrudescent SARS-CoV-2 infection.
Timepoint [5] 417286 0
Adverse events will be monitored throughout the study and assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTAE). COVID-19 symptoms will be captured daily and graded through use of a participant diary.
Secondary outcome [6] 417287 0
To determine the efficacy of BIT225 when dosed at 200 mg, 400 mg per day, or matching placebo administered for 7 consecutive days in individuals diagnosed with SARS-CoV-2 within 3 days of the onset of symptoms, based on multiple immunological outcome measures. disease-specific immune and inflammatory markers, including CD8 counts, CD4/CD8 ratio, pro-inflammatory cytokines, including IL-1ß, IL-6, and markers of inflammation, such as sCD163. These markers will be assessed as a composite outcome and are exploratory in nature.
Timepoint [6] 417287 0
Blood samples for detection of immune activation and inflammatory markers will be collected from all participants at Screening and Day 7, and follow-up Day 21 post-intervention commencement and will be determined by enzyme linked immunosorbent assay (ELISA).

Eligibility
Key inclusion criteria
1. Non-hospitalised, males or females aged 18-59 years with symptoms of mild to moderate SARS-CoV-2, including any cough, sore throat, fever, chills, nasal discharge, shortness of breath, fatigue, myalgias, malaise, headache, nausea, vomiting, diarrhea, alteration of taste or smell, that in the opinion of the Investigator are consistent with a presumptive diagnosis of SARS-CoV-2.

2. Rapid Antigen Test or PCR evidence confirming infection with SARS-CoV-2; documentation of a positive test within the past 24 hours.

3. Symptoms of =/< 3 days consistent with acute SARS-CoV-2 infection.

4. Room air oxygen saturation >/= 93%

5. Participants may have mild or well controlled comorbid conditions.

6. SARS-CoV-2 vaccinated, or unvaccinated individuals will be eligible for screening and enrolment.

7. Females of reproductive potential (defined as women who have not been post-menopausal for at least 12 consecutive months, i.e., who have had menses within the preceding 12 months, or women who have not undergone surgical sterilisation via hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy and/or tubal ligation), must:
Have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL at Screening

8. All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant, or to impregnate, sperm donation, in vitro fertilization). If participating in sexual activity that could lead to pregnancy, the participant and partner must agree to use reliable methods of contraception while receiving study treatment.

9. Participants who are not of reproductive potential (women who have been post-menopausal for at least 12 consecutive months or have undergone hysterectomy, bilateral salpingotomy, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives.

10. Provide written informed consent to participate in the study and be willing to comply with the study procedures
Minimum age
18 Years
Maximum age
59 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Individuals who would be excluded following the current Thai Ministry of Public Health (MOPH) COVID-19 National Guidelines.

2. In the opinion of the investigator, any participant who is likely to require hospitalisation, for any reason, within the next 48 hours.

3. Participants who have received non-vaccination treatment for SARS-CoV-2 within 30 days prior to study entry, e.g., remdesivir, Paxlovid, molnuparivir, SARS-CoV-2 monoclonal Abs, convalescent serum, or other anti- SARS-CoV-2 agents with national regulatory approval, zinc, or Andrographis paniculata.

4. Known current, or past, history of clinically significant arrhythmia.

5. Screening ECG QTcF value >/= 450 ms.

6. Pregnancy or breastfeeding.

7. Serious illness, that in the opinion of the site Investigator, is not considered medically stable.

8. Hospitalisation, for any reason, within the past 7 days.

9. The consumption / administration of excluded concomitant medication at the time of the Screening visit or during the treatment course of the study.

10. Active drug or alcohol use or dependence that, in the opinion of the site Investigator, would interfere with adherence to study requirements or compromise participant safety.

11. Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation

12. Presence of a condition, that in the opinion of the Investigator, would place the participant at increased risk from study participation, or compromise data integrity.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be assigned to treatment in accordance with the randomisation schedule following confirmation of eligibility on day 1. An unblinded pharmacist at the site will dispense the study medication to the blinded site staff according to the randomisation schedule. The dispensed medication will carry the participant's unique study number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Allocation of treatment is in a ratio of 2:1, BIT225 to placebo
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
8/05/2023
Actual
Date of last participant enrolment
Anticipated
14/07/2023
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment outside Australia
Country [1] 25197 0
Thailand
State/province [1] 25197 0

Funding & Sponsors
Funding source category [1] 312918 0
Commercial sector/Industry
Name [1] 312918 0
Biotron Limited
Country [1] 312918 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Biotron Limited
Address
Suite 3.3
56 Delhi Road
North Ryde NSW 2113
Country
Australia
Secondary sponsor category [1] 314595 0
None
Name [1] 314595 0
Address [1] 314595 0
Country [1] 314595 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312191 0
Institutional Review Board, Faculty of Medicine, Chulalongkorn University
Ethics committee address [1] 312191 0
1873 Rama 4 Road
Pathumwan,
Bangkok 10330 Thailand
Ethics committee country [1] 312191 0
Thailand
Date submitted for ethics approval [1] 312191 0
16/01/2023
Approval date [1] 312191 0
30/03/2023
Ethics approval number [1] 312191 0
Ethics committee name [2] 312941 0
Centre for Ethics in Human Research, Khon Kaen University
Ethics committee address [2] 312941 0
17th floor, Sor Vor 1 Building,
Faculty of Medicine, Khon Kaen University
123 Mittraphap Road
Nai Muang Subdistrict
Muang District, Khon Kaen, Thailand 40002
Ethics committee country [2] 312941 0
Thailand
Date submitted for ethics approval [2] 312941 0
03/02/2023
Approval date [2] 312941 0
05/04/2023
Ethics approval number [2] 312941 0

Summary
Brief summary
The proposed study will allow for an initial assessment of the safety, tolerability, and antiviral activity of multiple doses of BIT225 in SARS-CoV-2 infected patients.

The proposed study in SARS-CoV-2 will expand the knowledge of the antiviral and immune-modulatory capabilities of BIT225, and determine potential benefits to SARS-CoV-2 infected individuals. The role of BIT225 will be investigated in this proposed study of SARS-CoV-2 infected individuals, with special attention on immune and inflammatory activation markers, viral decay kinetics and time to resolution of symptoms.

This study aims to demonstrate if treatment with BIT225 within 3 days of onset of COVID-19 symptoms will result in reduction in SARS-CoV-2 plasma viral load, clinically favourable changes in viral, inflammatory and immune activation markers, as well as improvement in clinical symptoms of COVID-19 infection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123794 0
Dr Anchalee Avihingsanon
Address 123794 0
HIV-NAT, Thai Red Cross AIDS Research Centre
104 Ratchadamri Rd Pathumwan,
Bangkok, 10330, Thailand
Country 123794 0
Thailand
Phone 123794 0
+66 2 652 6040
Fax 123794 0
+66 2 252 5779
Email 123794 0
[email protected]
Contact person for public queries
Name 123795 0
Michelle Miller
Address 123795 0
Biotron Limited
Suite 3.3, 56 Delhi Rd
North Ryde NSW 2113
Australia
Country 123795 0
Australia
Phone 123795 0
+61 2 9805 0488
Fax 123795 0
+61 2 9805 0688
Email 123795 0
[email protected]
Contact person for scientific queries
Name 123796 0
Michelle Miller
Address 123796 0
Biotron Limited
Suite 3.3, 56 Delhi Rd
North Ryde NSW 2113
Australia
Country 123796 0
Australia
Phone 123796 0
+61 2 9805 0488
Fax 123796 0
+61 2 9805 0688
Email 123796 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.