Clinical Trial of Efficacy and Safety of ММН-407 in Acute Respiratory Viral Infection

Multicenter Double-blind Placebo-controlled Parallel Group Randomized Clinical Trial of Efficacy and Safety of MMH-407 in the Treatment of Acute Respiratory Viral Infection

To evaluate the efficacy and safety of ММН-407 in treatment of acute respiratory viral infection (ARVI).

Study Overview

• Status: Completed
• Conditions: Viral Respiratory Infection
• Intervention / Treatment: Drug: MMH-407; Drug: Placebo

Detailed Description

Design: multicenter, double blind, placebo-controlled, parallel group randomized clinical trial.

The study will enroll outpatients of either gender aged 18-70 years old with clinical manifestations of ARVI within the first day after the onset of the disease during seasonal ARVI morbidity.

After signing patient information sheet and informed consent form, medical history, thermometry, objective examination, laboratory tests and concomitant medication will be performed. Severity of ARVI symptoms is evaluated with 4-point scale.

The nasopharyngeal swabs for PCR diagnosis and verification of respiratory viruses will be performed prior to therapy to confirm the viral etiology of ARVI.

If a patient meets all inclusion criteria and does not have any exclusion criteria, at Visit 1 (Day 1) he/she will be randomized into one of two groups: the 1st group will take MMH-407 according to the dosage regimen for 5 days; the 2nd group will take Placebo according to MMH-407 dosage regimen for 5 days.

The study will use electronic patient diary for recording morning and evening axillary body temperature (measured using a mercury-free Geratherm Classic thermometer) and disease symptoms (Symptom Severity Score). Besides, antipyretic dosing (if applicable) and any aggravation in a patient's condition (if applicable, for safety evaluation/AE documentation) will also be recorded in a patient diary. The investigator will provide instructions on filling the diary; at Visit 1 the patient together with a doctor will record ARVI symptom severity and body temperature in the diary.

Patient will be observed for 14 days (screening, randomization - Day 1, treatment period - 5 days, follow-up - up to 2 days; deferred "phone visit" - Day 14).

During the treatment and follow-up period the patients or investigators will make 3 visits and the fourth "phone visit" will be scheduled additionally: 1) visits by physician/patient - on Days 1, 5 and 7 (Visits 1, 2 and 3) - in a study center or at home; 2) "phone visit" (Visit 4) - on Day 14.

At Visits 2 and 3, the investigator will perform an objective examination, document changes in the symptoms and concomitant medications to check patient diaries. At Visit 3 compliance will be evaluated and laboratory tests will be performed. "Phone visit" is carried out to interview the patient about his/her condition, presence/absence of secondary bacterial/viral complications and use of antibiotics.

During the study, symptomatic therapy and therapy for their co-morbidities are allowed with the exception of the drugs indicated in the section "Prohibited Concomitant Treatment".

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Barnaul, Russian Federation, 656038
    • Altai State Medical University, Department of Faculty Therapy with a course of immunology and allergology
  • Barnaul, Russian Federation, 656045
    • City Hospital #5
  • Belgorod, Russian Federation, 308015
    • Belgorod State National Research University, Hospital Therapy Department
  • Chelyabinsk, Russian Federation, 454000
    • Road Clinical Hospital at Chelyabinsk station of JSC Russian Railways
  • Izhevsk, Russian Federation, 426063
    • City Clinical Hospital #9 of the Ministry of Health of the Udmurt Republic
  • Kazan, Russian Federation, 420012
    • Kazan State Medical University, Internal Medicine Department
  • Kazan, Russian Federation, 420012
    • Kazan State Medical University, Professorial clinic
  • Krasnodar, Russian Federation, 350063
    • Kuban State Medical University, Infectious Diseases and PhthisiopulmonologyDepartment
  • Moscow, Russian Federation, 117593
    • Central Clinical Hospital of the Russian Academy of Sciences
  • Moscow, Russian Federation, 127473
    • Moscow State Medical and Dental University named after A.I. Evdokimov, Pulmonology Laboratory
  • Nizhniy Novgorod, Russian Federation, 603140
    • Road Clinical Hospital at the station Nizhny Novgorod of JSC Russian Railways
  • Nizhny Novgorod, Russian Federation, 603011
    • City Clinical Hospital #10 of the Kanavinsky District of Nizhny Novgorod
  • Podolsk, Russian Federation, 142105
    • Podolsk City Clinical Hospital # 3
  • Rostov-on-Don, Russian Federation, 344068
    • City Emergency Hospital Rostov-on-Don
  • Ryazan, Russian Federation, 390026
    • Ryazan State Medical University named after academician I.P. Pavlov, Department of Outpatient Therapy and Preventive Medicine
  • Saint Petersburg, Russian Federation, 191180
    • Vvedensky City Clinical Hospital
  • Saint Petersburg, Russian Federation, 193312
    • City Polyclinic #25 of the Nevsky District
  • Saint Petersburg, Russian Federation, 194354
    • Medical Center "Reavita Med SPb"
  • Saint Petersburg, Russian Federation, 195271
    • Road Clinical Hospital of JSC Russian Railways
  • Saint Petersburg, Russian Federation, 196211
    • City Polyclinic #51
  • Saint Petersburg, Russian Federation, 197198
    • City Polyclinic #34
  • Saint Petersburg, Russian Federation, 198207
    • City polyclinic #43
  • Samara, Russian Federation, 443056
    • Samara city hospital #4
  • Stavropol, Russian Federation, 355000
    • Scientific Medical Center for General Therapy and Pharmacology
  • Ufa, Russian Federation, 450008
    • Bashkir State Medical University, Internal Medicine Department
  • Volgograd, Russian Federation, 400131
    • Volgograd State Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients of either gender aged 18-70 years.
2. Diagnosis of ARVI based on medical examination: axillary temperature ≥ 38.0°C at examination + total general symptoms score ≥4, nasal/throat/chest symptoms score ≥2.
3. The first 24 hours after ARVI onset.
4. Patients giving their consent to use reliable contraception during the study.
5. Signed patient information sheet (informed consent form).

Exclusion Criteria:

1. Clinical symptoms of severe influenza/ARVI requiring hospitalization.
2. Suspected pneumonia, bacterial infection (including otitis media, sinusitis, urinary tract infection, meningitis, sepsis, etc.) requiring administration of antibiotics from the first day of illness.
3. Suspected initial manifestations of diseases with symptoms similar to ARVI at onset (other infectious diseases, flu-like syndrome at the onset of systemic connective tissue diseases, and other pathology).
4. Patients requiring antiviral medication prohibited within the study.
5. Medical history of primary and secondary immunodeficiency.
6. Medical history/suspicion of oncology of any localization (except for benign neoplasms).
7. Aggravation or decompensation of chronic diseases affecting a patient's ability to participate in the clinical trial.
8. Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
9. Allergy/ hypersensitivity to any component of the study drug.
10. Pregnancy, breast-feeding; childbirth less than 3 months prior to the inclusion in the trial, unwillingness to use contraceptive methods during the trial.
11. Course administration of the drug products specified in the section "Prohibited Concomitant Therapy" within two weeks prior to inclusion in the study.
12. Patients who will not fulfill the requirements during the study or follow the order of administration of the studied drug products, from the Investigator's point of view.
13. Medical history of mental diseases, alcoholism or drug abuse that according to the investigator's opinion will compromise compliance with the study procedures.
14. Participation in other clinical trials for 3 months prior to enrollment in this study.
15. Patients who are related to any of the on-site research personnel directly involved in the study or are an immediate relative of the investigator. 'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted).
16. Patients who work for OOO "NPF "MATERIA MEDICA HOLDING" (i.e. the company's employees, temporary contract workers, designated officials responsible for carrying out the research or any immediate relatives of the aforementioned).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMH-407; Tablet for oral use. One tablet per intake. On day 1, five tablets are taken in the first 2 hours (one tablet every 30 min), followed by three more tablets regularly spaced during the rest of the day. From day 2 through 5, one tablet is administered three times daily. The drug is administered not during meals (i.e. between the meals or 15-30 minutes before meal). The tablet should be held in mouth until complete dissolution.	Drug: MMH-407; Oral use.; Other Names: Raphamin
Placebo Comparator: Placebo; According to the scheme of receiving MMN-407 until the end of the study.	Drug: Placebo; Oral use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Resolution of Acute Respiratory Viral Infection (ARVI) Symptoms	Outcome Measure is evaluated on the basis of the "ARVI severity scale" to calculate total symptom score (TSS) in patients with confirmed virus by Polymerase chain reaction (PCR). ARVI's resolution criteria: temperature ≤37.3°С + TSS ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), and 6 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TSS absolute axillar temperature (in degrees Celsius) was converted to relative units (or points) using the following scale: ≤37.3 С=0 points; 37.4-38.0 С=1 point; 38.1-39.0 С=2 points; ≥39.1 С=3 points. The range of TSS was from "0" to "39".	14 days of observation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of ARVI (Clinically Diagnosed and/or PCR-confirmed)	Outcome Measure is based on the area under the curve (AUC) for TSS. AUC was calculated between 6 points (by TSS for every 6 days of the treatment and observation). The minimum value for the AUC was "0" and the maximum value was "234" units (day*score). Higher TSS and AUC scores meant worse results.	On days 1- 6 of the observation.
Percentage of Patients With Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed)	ARVI's resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 6 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TSS absolute axillar temperature (in degrees Celsius) was converted to relative units (or points) using the following scale: ≤37.3 С=0 points; 37.4-38.0 С=1 point; 38.1-39.0 С=2 points; ≥39.1 С=3 points. The range of TSS was from "0" to "39".	On days 3, 4, 5 and 6 of observation.
Time to Resolution of Acute Respiratory Viral Infection Symptoms (Clinically Diagnosed and/or PCR-confirmed)	Acute Respiratory Viral Infection (ARVI) Symptoms resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 6 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TSS absolute axillar temperature (in degrees Celsius) was converted to relative units (or points) using the following scale: ≤37.3 С=0 points; 37.4-38.0 С=1 point; 38.1-39.0 С=2 points; ≥39.1 С=3 points. The range of TSS was from "0" to "39".	14 days of observation.
Percentage of Patients With Resolution of Acute Respiratory Viral Infection (PCR-confirmed)	Outcome Measure is based on the Percentage of Patients With Resolution of Acute Respiratory Viral Infection, confirmed by Polymerase chain reaction (PCR), i.e virus detection. Acute Respiratory Viral Infection resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 6 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TSS absolute axillar temperature (in degrees Celsius) was converted to relative units (or points) using the following scale: ≤37.3 С=0 points; 37.4-38.0 С=1 point; 38.1-39.0 С=2 points; ≥39.1 С=3 points. The range of TSS was from "0" to "39".	On days 3, 4, 5 and 6 of observation.
Dosing Frequency of Antipyretics.	Outcome Measure is based on the rates of antipyretic use per patient during days 1 to 3 of therapy.	On days 1, 2, 3 of therapy.
Percentage of Patients Reporting Worsening of Illness	Outcome Measure is based on the rates of Complications that require the use of antibiotics or hospitalization.	From day 4 to day 14 of the observation period.
Occurrence and Characteristics of Adverse Events (AEs)	Severity of AEs, its causal relationship to the study drug, and outcomes.	From day 1 to day 7 of the treatment period.
Changes in Vital Signs: Blood Pressure.	Outcome Measure is based on the medical records. Blood Pressure was measured by the physician in every visit (on days 1, 5, and 7).	On days 1, 5 and 7 of the treatment period.
Changes in Vital Signs: Pulse Rate (Heart Rate).	Outcome Measure is based on the medical records. Pulse Rate (Heart Rate) was measured by the physician in every visit (on days 1, 5, and 7).	On days 1, 5 and 7 of the treatment period.
Changes in Vital Signs: Respiration Rate (Breathing Rate).	Outcome Measure is based on the medical records. Respiration Rate (Breathing Rate) was measured by the physician in every visit (on days 1, 5, and 7).	On days 1, 5 and 7 of the treatment period.
Percentage of Patients With Clinically Relevant Laboratory Abnormalities	Outcome Measure is based on the Hematology, blood chemistry, and urinalysis parameters, which were beyond the reference values at the end of treatment.	From day 1 to day 7 of the treatment period.

Collaborators and Investigators

• Sponsor: Materia Medica Holding

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2019
• Primary Completion (Actual): April 9, 2020
• Study Completion (Actual): April 9, 2020

Study Registration Dates

• First Submitted: December 13, 2019
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Virus Diseases; Respiratory Tract Infections
• Other Study ID Numbers: MMH-407-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No