Clinical trial NCT04682444: Efficacy and Safety of Enisamium Iodide for the Treatment of Acute Respiratory Viral Infections, Including Influenza.
Official title: A Prospective Single-blind Comparative Clinical Study of Efficacy and Safety of Amizon 0.25 g Tablets, Manufactured by Farmak JSC, in Patients With ARVI, Including Influenza.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Respiratory Viral Infections
Human Influenza
Keywords: Viral infections
Amizon
Enisamium iodide
Influenza
Lead sponsor: Joint Stock Company "Farmak"
Sponsor class: INDUSTRY
First posted: 2020-12-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, single blind clinical study was conducted to investigate the clinical efficacy and safety of the drug Amizon (enisamium iodide), in comparison with placebo for the treatment of patients with acute respiratory viral infections (ARVI), including influenza. Enisamium iodide is an antiviral small molecule.

Adult patients were enrolled and randomised into 2 groups. On the first day of the onset of symptoms of ARVI, one group of patients took Amizon tablets (active ingredient enisamium iodide) for 7 days; the other group of patients took matching placebo tablets for 7 days. Examination and observation of all participants was done for up to 14 days after the first intake of the study drug.

The effect of treatment was assessed by subjective reporting of the symptoms of ARVI and influenza, using a predefined symptom scale score system.

Objective assessment was performed by measuring vitals signs, laboratory tests (including blood and urine assessment), as well as evaluating the immune status (including measuring the relative concentration of interferon and immunoglobulins).

Detailed description: Numerous studies have shown that influenza vaccines, prepared against the relevant epidemic seasonal vaccine strains, are an effective remedy in prevention of this mass disease and are able to protect about 80% of otherwise healthy children and adults. However, to develop vaccines against the emerging new pandemic strain of the influenza virus and produce them in the necessary amounts requires at least 6 months. During such interim periods, sufficient protection of the population is essential by effective measures for treatment and prevention of influenza.

This randomized, single-blind, clinical study was conducted to investigate the clinical efficacy and safety of the drug Amizon (N-methyl-4-benzylcarbamidopyridinium iodide, international nonproprietary name enisamium iodide) compared with placebo, for the treatment of patients with ARVI, including influenza.

Enisamium iodide is an antiviral small molecule. Enisamium can directly inhibit influenza viral RNA replication.

The study design was: randomised, single-blind, 2 parallel groups. Adult patients (18-60 y) with symptoms of ARVI, including influenza took either Amizon tablets (active ingredient enisamium iodide) for 7 days; in the control group patients took placebo tablets for 7 days. Study visits occurred on Day 0 (screening, examination, check inclusion/exclusion criteria, enrollment, randomization, and first intake of study drug); further study visits were on Day 3, Day 7, and Day 14.

The effect of treatment was assessed by questioning the patients regarding ARVI and influenza symptoms that included pain, headache, general weakness, sore throat, pain in the joints, fatigue, runny and itchy nose. The severity of symptoms was recorded using a 4-point Likert scale.

Further evaluation of the treatment was performed by measuring the vitals signs, laboratory tests that included blood and urine analysis, biochemical analysis, as well as assessing the immune status (including measuring the absolute lymphocytes count, and evaluating the relative concentration of interferon (IFN)-alpha and IFN-gamma, and immunoglobulins (IgA, IgM, and IgG).

Eligibility criteria: Inclusion Criteria:

* Patients aged between 18 to 60 years
* Patients with ARVI, including influenza, starting not later than for 1 day prior to inclusion in the study:
* The body temperature measured axillary above 37.2 °C
* Presence of one of the signs of respiratory disease (runny nose, cough, pain / tickling in the throat)
* Presence of one of the systemic symptoms (weakness, myalgia, headache , chills, sweating)
* Provide written informed consent
* Ability to understand the nature of the study and provide written informed consent in accordance with Good Clinical Practice (GCP) and local law

Exclusion Criteria:

* Age over 60 years and under 18 years old
* Presence of allergic reactions
* Intolerance to NSAIDs and iodine-containing drugs
* Hypersensitivity to the components of the drug
* Mental illness that impedes compliance with the research procedure
* Pregnancy or breast-feeding
* Presence of acute, clinically significant respiratory and cardio vascular insufficiency, functional disorders of liver, kidney, digestive tract (ulcer disease) determined at physical examination or by laboratory screening tests
* Presence of congenital defects or serious chronic disease of the lungs, kidneys, cardiovascular system, nervous system, metabolic disorders, psychiatric disorders, confirmed by patients history or during initial examination
* The use of preparations of blood cytokine immunoglobulin in for 3 months prior to the study
* Chronic use of alcohol and / or drugs
* Presence or history of cancer diseases, HIV, hepatitis B and C
* Application of immunosuppressive or immunomodulatory drugs for 6-months prior to the study
* Women of child-bearing potential and who do not use acceptable measure of contraception or do not plan to use those throughout the study
* Any clinical condition that, according to the investigator, will not allow to safely carry out the protocol and take the studied drugs without risk to health
* Patients receiving antiviral therapy,
* Participation in other clinical trials at the present time or during the last 3 months.

Primary outcomes:
measure: Efficacy - Clinical improvement from Day 3 after therapy start
timeFrame: Day 0, 3, 7, 14
Secondary outcomes:
measure: Efficacy - Time of disappearance of respiratory tract affection symptoms
timeFrame: Day 0, 3, 7, 14
measure: Efficacy - Body temperature normalization
timeFrame: Day 0, 3, 7, 14
measure: Efficacy - General symptoms of ARVI including influenza
timeFrame: Day 0, 3, 7, 14
measure: Efficacy - Viral antigens
timeFrame: Day 0, 3, 7
measure: Safety - Adverse events
timeFrame: Day 0 to Day 14
measure: Safety - Laboratory parameters - Immune status
timeFrame: Day 0, 7, 14
Other outcomes:
Locations:
Study officials:
affiliation: Smorodintsev Research Institute of Influenza
name: Ekatarina A. Okhapkina
role: PRINCIPAL_INVESTIGATOR
References:
citation: Te Velthuis AJW, Zubkova TG, Shaw M, Mehle A, Boltz D, Gmeinwieser N, Stammer H, Milde J, Muller L, Margitich V. Enisamium Reduces Influenza Virus Shedding and Improves Patient Recovery by Inhibiting Viral RNA Polymerase Activity. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02605-20. doi: 10.1128/AAC.02605-20. Print 2021 Mar 18.