Efficacy and Safety of Enisamium Iodide for the Treatment of Acute Respiratory Viral Infections, Including Influenza.

Phase 2

Completed

• Conditions: Acute Respiratory Viral Infections; Human Influenza
• Interventions: Drug: Enisamium Iodide; Drug: Placebo

• Registration Number: NCT04682444
• Lead Sponsor: Joint Stock Company "Farmak"

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).

Study Timeline

• Study Start: 2009-04-13
• Primary Completion: 2010-01-28
• Study Completion: 2010-05-15
• Status Verified: 2020-12
• Study First Submitted: 2020-12-17
• Study First Submitted QC: 2020-12-22
• Last Update Submitted: 2020-12-22
• Study First Posted: 2020-12-23
• Last Update Posted: 2020-12-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 - Active Treatment	Enisamium Iodide	Patient who were randomized into Group 1 ingested Amizon tablets 0.5 g (2 tablets) after a meal, 3 times a day, for 7 days; each tablet contains 0.25 g of enisamium iodide.
Group 2 - Placebo	Placebo	Patient who were randomized into Group 2 ingested placebo tablets after a meal, at the dose 0.5 g (2 tablets), 3 times a day, for 7 days.

Primary Outcome Measures

Name	Time	Method
Efficacy - Clinical improvement from Day 3 after therapy start	Day 0, 3, 7, 14	Evaluate the number of patients in the treatment and the placebo groups regarding clinical improvement from Day 3 after therapy start.; Clinical improvement was assessed by the investigator from scores of objective and subjective data, relating to the severity of clinical symptoms of ARVI, including influenza.; Objective symptoms were assessed using the following score system: normal or abnormal blood pressure was counted 0 or 4 score points; lung auscultation was counted 0 for vesicular breath sound and wheezing or crepitation were scored 2 or 4 points, respectively; clear and rhythmic heart sounds were each scored 0 points, whereas noisy and arrhythmic heart sounds were scored 2 points each.; The subjective symptoms were assessed using a 4-point Likert scale, ranging from 1 (absent) to 4 (severe).

Secondary Outcome Measures

Name	Time	Method
Efficacy - Time of disappearance of respiratory tract affection symptoms	Day 0, 3, 7, 14	Evaluate the time of disappearance of respiratory tract symptoms (rhinitis, pharyngitis, laryngitis, tracheitis, bronchitis, cough).; Evaluate the general state of health, condition of cutaneous coverings, oral mucosa and tonsils, peripheral lymph nodes, abdominal cavity organs, nervous and musculoskeletal system, lung and heart percussion and auscultation data were assessed.; Evaluate the intensity and duration of the disease symptoms: temperature response, catarrhal events in nasopharynx and other respiratory tract parts.; Clinical improvement was assessed by the visit day on which the symptoms were absent (score 1 on the Likert scale, as described for Outcome 1).
Efficacy - Body temperature normalization	Day 0, 3, 7, 14	Monitor body temperature.
Efficacy - General symptoms of ARVI including influenza	Day 0, 3, 7, 14	Time of disappearance of general symptoms -- ARVI, including influenza.; Time of disappearance of general symptoms relating to the respiratory tract, including weakness, headache, myalgia, chills, sore throat, and cough.
Efficacy - Viral antigens	Day 0, 3, 7	Viral antigens evaluated: influenza A and B, respiratory syncytial virus, adenovirus, parainfluenza virus.; Virus antigens were isolated from nasal swabs and detected by using validated immunofluorescence testing methods.; Efficacy assessment: evaluate viral antigen levels at the end of treatment (Day 7) versus the baseline data (Day 0) and compare with the placebo group.
Safety - Adverse events	Day 0 to Day 14	Adverse events occurring during the study were recorded daily by the patients into a patient dairy (Day 0 to Day 14). Clinically relevant laboratory parameters changes outside the normal range were also considered as adverse events.; The relationship of the adverse events to the intake of the investigational drug assessed by the investigator.
Safety - Laboratory parameters - Immune status	Day 0, 7, 14	Assessment of the immune status was performed by evaluating the concentration in blood serum of interferon \[IFN\]-alpha and IFN-gamma, immunoglobulin A, immunoglobulin M, immunoglobulin G.; Determination of immunoglobulins А, М, G was performed by turbidimetry. Determination of interferon-alpha and interferon-gamma in human blood serum was carried out using flow cytometer.