Clinical trial NCT04682873: A Clinical Study to Assess the Efficacy and Safety of Amizon® Max in the Treatment of Moderate Covid-19, Caused by the SARS-CoV-2 Virus
Official title: A Multi-centre, Double-blind, Randomised, Placebo-controlled, Trial to Assess the Efficacy and Safety of Amizon® Max, Manufactured by Farmak JSC, in Combination With Basic Treatment, in Subjects With Moderate Covid-19, Which is Caused by the SARS-CoV-2 Virus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Covid-19 Disease
Keywords: Amizon
Antiviral
Covid-19
Enisamium iodide
Ukraine
FAV00A
Lead sponsor: Joint Stock Company "Farmak"
Sponsor class: INDUSTRY
First posted: 2020-12-24
Enrollment: 592
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Adult female and male patients, hospitalized with Covid-19 infection (confirmed by reverse transcription polymerase chain reaction \[RT-PCR\]), will be screened for participation in this prospective, multi-center, double-blind, randomised, placebo-controlled trial.

Enrolled patients will be randomized (1:1) into 2 treatment groups: Group 1 will receive the active treatment with Amizon® Max (international nonproprietary name enisamium iodide), one capsule (each containing 500 mg of enisamium iodide) 4 times daily every 6 hours for 7 days; patients in treatment Group 2 will receive a matching placebo capsule, 4 times daily every 6 hours for 7 days. Patient observation and follow-up are planned for 29 days, unless discharged before Day 29.

The effect of treatment on Covid-19 will be evaluated by time from day of randomization to an increase of at least two points (from the status at randomization) on the severity rating scale (SR), the Time to Clinical Recovery (TTCR) of main Covid-19 symptoms / complications and the Sum of Severity Rating from Day 2 to Day 15 (SSR-15). Safety and tolerability of the study drug will be evaluated based on the intensity and course of adverse events (Es).

Enisamium iodide is an antiviral small molecule. Enisamium inhibits replication of alpha- and beta- coronaviruses (human coronavirus NL63 and SARS-CoV-2, respectively) and influenza virus A and B. Mechanism of action against SARS-CoV-2 includes the direct inhibition of the viral RNA polymerase.

Detailed description: This randomized, prospective, multi-center, double-blind, placebo-controlled trial, is conducted to investigate the clinical efficacy and safety of the drug Amizon® Max (N-methyl-4-benzylcarbamidopyridinium iodide, international nonproprietary name enisamium iodide, lab code FAV00A) in comparison with placebo, for the treatment of hospitalized patients with RT-PCR confirmed Covid-19 infection.

Enisamium iodide is an antiviral small molecule. Enisamium can directly inhibit influenza viral RNA replication and has antiviral effect against viruses, including coronaviruses (human coronavirus NL63, SARS-CoV-2).Based on the promising in-vitro anti-SARS-CoV-2 activity, it could be assumed that patients suffering from Covid-19 would benefit from a reduced virus load and this could lead to a reduction of Covid-19 typical symptoms that might prevent further complications associated with severe Covid-19 (e.g. active mechanical ventilation).

Adult female and male patients, with Covid-19 infection, will be screened (Day 1) to participate in this trial. If all inclusion/exclusion criteria are fulfilled, randomization to treatment and a start of treatment will occur on Day 1.

Patients will be randomized into 2 treatment groups (1:1) as follows: patients in treatment Group 1 will receive the active treatment with Amizon® Max capsule; patients in treatment Group 2 will receive a placebo capsule. The active treatment and placebo capsules are identical in appearance and size.

Patients will take Amizon® Max capsules 500 mg (active ingredient enisamium iodide) 4 times a day every 6 hours (total daily dose 2,000 mg) for full 7 days. In the control group, patients will take placebo tablets 4 times a day for full 7 days. Patient observation interval is for as long as a subject is hospitalized Day 1 to Day 29. A follow-up visit will be performed on Day 29 (by phone as applicable for all subjects discharged from the hospital before Day 29).

The effect of treatment on Covid-19 will be evaluated by the time from the day of randomization (Day 0) to an improvement of at least two points (from the status at randomization) on the severity rating scale (SR), the Time to Clinical Recovery (TTCR) of main Covid-19 symptoms / complications and the Sum of Severity Rating from Day 2 to Day 15 (SSR-15).

Additional outcome measures of efficacy include the 'Days Alive' and 'Out of Hospital' from Day 1 until Day 15 (DAOH-14), the proportion of subjects discharged by Day 8, 15, 22, and 29, the incidence of complications (i.e. pneumonia, need for transfer to intensive care unit \[ICU\]), the incidence and days until occurrence of pneumonia, incidence and days until supplemental oxygen / high flow oxygen, incidence and days until (non-invasive / invasive mechanical ventilation), incidence and days until transfer to ICU, incidence and time to death, time to virus free, measurement of vital signs (i.e. fever (body temperature), respiratory rate, peripheral capillary oxygen saturation \[SpO2\]) and the course of symptoms of Covid-19.

Symptom severity for headache, sore throat, cough, shortness of breath, rhinorrhoea, fatigue, myalgia, diarrhoea will be monitored. Safety and tolerability of the study drug will be evaluated based on the intensity and course of adverse events (AEs), safety laboratory tests, as well as the investigator's and subject's overall assessment of tolerability of the treatment.

Eligibility criteria: Inclusion Criteria:

Each subject must meet all of the following inclusion criteria to be randomized to treatment:

1. Willing and able to provide written informed consent
2. Aged ≥ 18 years
3. SARS-CoV-2 infection confirmed by PCR ≤ 4 days before randomization
4. Currently hospitalized due to SARS-CoV-2 infection with fever, defined as body temperature ≥ 37.8 °C
5. Modified World Health Organization (WHO) Ordinal Scale for Clinical Status Patient state in Covid-19: score 4 i.e. hospitalized, virus-positive, oxygen by mask or nasal prongs

Exclusion Criteria:

The subject is excluded from the trial if any of the following criteria apply:

1. Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited \< 24 hours prior to start of IMP treatment
2. Requiring mechanical ventilation at screening or it is expected within 24 h after inclusion
3. Expected survival time \< 72 hours for any reason
4. Positive pregnancy test
5. Breastfeeding woman
6. Presence of renal dysfunction defined as estimated glomerular filtration rate (eGFR) \<60 mL/min, total bilirubin ≥ 2.0 mg/dL, Thyroid stimulating hormone (TSH) outside normal range and / or Aspartate aminotransferase (ASAT)/ Alanine aminotransferase (ALAT) above threefold upper limit of normal range (known from patients medical history)
7. Known hypersensitivity to the trial drug, the metabolites, or formulation excipient
8. History or presence of drug or alcohol abuse
9. History or presence of diseases of thyroid gland

Primary outcomes:
measure: Efficacy - Time from day of randomization to an improvement of at least two points (from the status at randomization) on severity rating (SR) scale in days
timeFrame: Day 0 to Day 29
Secondary outcomes:
measure: Efficacy - Time to recovery (TTR) from Day 1 (randomization and start of IMP treatment)
timeFrame: Day 0 to Day 29
measure: Time to Clinical Recovery (TTCR) of main Covid-19 symptoms/complications or discharge
timeFrame: Day 0 to Day 29
measure: Sum of Severity Rating from Day 2 to Day 15 (SSR-15)
timeFrame: Day 2 to Day 15
measure: Severity Rating on Day 15 (SR-15):
timeFrame: Day 15 or Day of discharge (whichever occurs first)
measure: Days Alive and Out of Hospital until Day 15 (DAOH-14)
timeFrame: Day 2 to Day 15
measure: Proportion of Subjects Discharged by Day 8, 15, 22, 29
timeFrame: Day 0 to Day 29
measure: Incidence of non-invasive ventilation
timeFrame: Day 0 to Day 29
measure: Days until non-invasive ventilation
timeFrame: Day 0 to Day 29
measure: Total days of non-invasive ventilation
timeFrame: Day 0 to Day 29
measure: Incidence of invasive mechanical ventilation or ECMO
timeFrame: Day 0 to Day 29
measure: Days until invasive mechanical ventilation or ECMO
timeFrame: Day 0 to Day 29
measure: Course of qualitative RT-PCR viral test results
timeFrame: Day 0 to Day 29
measure: Viral test evaluation - Proportion of subjects free of SARS-CoV-2
timeFrame: Days 0, 8, 15, 22, 29
measure: Overall assessment of efficacy (patient and investigator)
timeFrame: Day 29 or Day of discharge (whichever occurs first)
measure: Adverse events (AEs)
timeFrame: Day 0 to Day 29
measure: Overall assessment of tolerability of treatment (patient and investigator)
timeFrame: Day 29 or Day of discharge (whichever occurs first)
Other outcomes:
Locations:
city: Lutsk
country: Ukraine
facility: Municipal Enterprise "Volyn Regional Clinical Hospital" of Volyn Regional Council, Dept. Pulmonology
state: Volynsk
city: Chernivtsi
country: Ukraine
facility: Municipal Non-Commercial Enterprise 'City Clinical Hospital #3' Chernivtsi City Council, Dept. Therapeutics #1, Dept. Therapeutics #2, Higher State Educational Institution of Ukraine 'Bukovinian State University'
city: Ivano-Frankivsk
country: Ukraine
facility: Municipal Non-Commercial Enterprise 'Regional Clinical Infection Hospital Ivano-Frankivsk Regional Council', Dept. #2, Ivano-Frankivsk National Medical University
city: Ivano-Frankivsk
country: Ukraine
facility: Municipal Non-Commercial Enterprise 'Regional Clinical Hospital Ivano-Frankivsk Regional Council', Dept. Allergology
city: Ivano-Frankivsk
country: Ukraine
facility: Municipal Non-Commercial Enterprise 'City Clinical Hospital #1 Ivano-Frankivsk City Council', Dept. Therapeutics
city: Kharkiv
country: Ukraine
facility: Municipal Non-Commercial Enterprise Kharkiv Regional Council 'Regional Clinical Infection Hospital', 1st Department, Kharkiv National Medical University, Chair of Infectious Diseases
city: Kyiv
country: Ukraine
facility: Municipal Non-Commercial Enterprise 'Olexandrivska Clinical Hospital of Kyiv' Executive Authority of Kyiv City Council, Dept. Infections
city: Kyiv
country: Ukraine
facility: Municipal Non-Commercial Enterprise "Kyiv City Clinical Hospital #9" Executive Authority of Kyiv City Council, Dept. Infections
city: Lviv
country: Ukraine
facility: Municipal Non-Commercial Enterprise Lviv Regional Council 'Lviv Regional Infection Hospital', Fourth Diagnostic Department
city: Poltava
country: Ukraine
facility: Ukraine Medical Stomatological Academy, Chair of Infectious Diseases with Epidemiology, Municipal Non-Commercial Enterprise 'Poltava Regional Infection Hospital Poltava Regional Council', Dept. Respiratory Infections
city: Rivne
country: Ukraine
facility: Municipal Non-Commercial Enterprise 'Central Clinical Hospital' of Rivne City Council, Hepatic Centre - Infections
city: Uzhhorod
country: Ukraine
facility: Municipal Non-Commercial Enterprise 'Regional Clinical Infectional Hospital' Transcarpathian Regional Council, Dept. Infections (Adult)
city: Vinnytsya
country: Ukraine
facility: Municipal Non-Сommercial Enterprise 'Vinnytsya City Clinical Hospital #1', Infectious Department, National Pirogov Memorial Medical University, Dept. Infections
Study officials:
affiliation: Head of Department of Infectious Diseases; O.O. Bogomolets National Medical University; Kyiv Ukraine
name: Olha Holubovska, MD, DSc
role: PRINCIPAL_INVESTIGATOR
References: