A Study To Evaluate The Efficacy And Safety Of a Novel Niclosamide Suspension Formulation For COVID-19

The study will be performed in accordance with the relevant articles of the Declaration of
Helsinki (1964) as revised in Tokyo (1975), Venice (1983), Hong Kong (1989), Somerset West,
RSA (1996), Edinburgh (2000), Washington (2002), Tokyo (2004) and Seoul (2008) and Fortaleza
(2013).

The medications for the established treatment regimen will be supplied by Ministry of Health
to the study sites. The other study medications, Investigational product and placebo,
together with relative documentation, will be supplied to clinical sites by the sponsor.
Niclosamide 200 mg/10 mL Suspension and placebo will be supplied together with certificates
of analysis by the company responsible for manufacturing of the test product(s).The packaging
and labelling of niclosamide and placebo will be done according to the GMP and GCP
requirements.

All subjects will receive either 200 mg/10 mL niclosamide suspension or 10 mL placebo three
times a day for 5 days, together with an established COVID-19 treatment regimen according to
the official guidance for COVID-19 Adult Treatment Algorithm of Republic of Turkey Ministry
of Health. Dosings will be administered in accordance with the treatment randomization table
throughout the treatment duration.

On each drug administration, the identity of the subject will be confirmed by checking the
Identity Card. Administration of the study medication will be performed by the
investigator(s) and nurse(s) and supervised by a second medical professional to ensure the
correctness of drug administration. Also, a monitor may attend during this procedure. The
administration of the study medication is to be followed by a mouth check, to be documented
in the CRF and certified by the Investigator.

The statistical analysis will be done according to the provisions of ICH Topic E9,
Statistical Principles for Clinical Trials (CPMP/ICH/363/96), September 1998.

Statistical analysis will be performed as a valid case analysis including all subjects in
which no major protocol deviations occurred and all primary target variables are available
for measurement.

If a subject is to be excluded from evaluation, this decision has to be justified in the
Final Study Report.

Continuous variables will be expressed as means ± standard deviations (SD) for the normally
distributed data or median with interquartile (IQR) for the skewed data. Correspondingly,
two-sample independent t-test and Mann-Whitney U test will be used to detect the difference
between groups. Categorical variables will be described as number (%) and compared by χ² test
or Fisher's exact test as appropriate. Kaplan-Meier method will be used to estimate the
cumulative probability of the endpoint. Cox proportional hazards regression model will be
conducted to determine the potential risk factors associated with the endpoint. Statistical
significance will be defined as p<α=0.0054 for interim analysis, p<α=0.0492 for final
analysis using O'Brien-Fleming alpha adjustment. All analyses will be done with R project.

The expected percentage of treatment success is 75% in the experimental group and 50% in the
control group. The sample size calculation yields that 170 subjects are needed (85 for each
group) to achieve 90% power at α=0.05. Considering potential dropouts, the sample size is
estimated as 200 subjects (100 subjects for each group). For interim analysis, 100 subjects
(50 subjects for each group) will be evaluated.

Before being enrolled to the clinical study, the subject(s) must consent to participate in
the study by signing the informed consent form in response to a complete written and verbal
explanation of the nature, scope and possible consequences of the clinical study explained in
an understandable way for him/her by the physician.

Each subject will give in writing her/his authorization that the study data may be given for
review to the responsible Local and National Authorities.

The subject information and informed consent form will be provided in duplicate [one signed
version (original 1) will be left at the investigator; the other signed version (original 2)
will be forwarded to the subject].