Clinical Trial of Efficacy and Safety of ММН-407 in Acute... | NCT04244084

Status Module

Description Module

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".

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MMH-407	Experimental	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
Placebo	Placebo Comparator	According to the scheme of receiving MMN-407 until the end of the study.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
MMH-407	Drug	Oral use.	MMH-407	Raphamin

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients of either gender aged 18-70 years.
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.
The first 24 hours after ARVI onset.
Patients giving their consent to use reliable contraception during the study.
Signed patient information sheet (informed consent form).

Exclusion Criteria:

Clinical symptoms of severe influenza/ARVI requiring hospitalization.
Suspected pneumonia, bacterial infection (including otitis media, sinusitis, urinary tract infection, meningitis, sepsis, etc.) requiring administration of antibiotics from the first day of illness.
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).
Patients requiring antiviral medication prohibited within the study.
Medical history of primary and secondary immunodeficiency.
Medical history/suspicion of oncology of any localization (except for benign neoplasms).
Aggravation or decompensation of chronic diseases affecting a patient's ability to participate in the clinical trial.
Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
Allergy/ hypersensitivity to any component of the study drug.
Pregnancy, breast-feeding; childbirth less than 3 months prior to the inclusion in the trial, unwillingness to use contraceptive methods during the trial.
Course administration of the drug products specified in the section "Prohibited Concomitant Therapy" within two weeks prior to inclusion in the study.
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.
Medical history of mental diseases, alcoholism or drug abuse that according to the investigator's opinion will compromise compliance with the study procedures.
Participation in other clinical trials for 3 months prior to enrollment in this study.
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).
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).

Facility	Status	City	State	ZIP	Country	Contacts
Altai State Medical University, Department of Faculty Therapy with a course of immunology and allergology		Barnaul		656038	Russia

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 1, 2019

Arm/Group Information

ID	Title	Description
BG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
BG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0004.1± 1.9 OG0015.0± 2.5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Mean differences (MMH-407 vs. Placebo) were compared	ANCOVA	Site used as covariate	0.0155		Median Difference (Final Values)	-0.89			2-Sided	95	-1.61	-0.17					Superiority

Secondary

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.

Posted

Mean

Standard Deviation

day*score

On days 1- 6 of the observation.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Units	Counts
Participants

Secondary

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".

Posted

Count of Participants

Participants

On days 3, 4, 5 and 6 of observation.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Secondary

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".

Posted

Mean

Standard Deviation

days

14 days of observation.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Secondary

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".

Posted

Count of Participants

Participants

On days 3, 4, 5 and 6 of observation.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo

Secondary

Dosing Frequency of Antipyretics.

Outcome Measure is based on the rates of antipyretic use per patient during days 1 to 3 of therapy.

Posted

Mean

Standard Deviation

number of doses

On days 1, 2, 3 of therapy.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Reporting Worsening of Illness

Outcome Measure is based on the rates of Complications that require the use of antibiotics or hospitalization.

Posted

Count of Participants

Participants

From day 4 to day 14 of the observation period.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Units	Counts
Participants	OG000

Secondary

Occurrence and Characteristics of Adverse Events (AEs)

Severity of AEs, its causal relationship to the study drug, and outcomes.

Posted

Number

Number of events

From day 1 to day 7 of the treatment period.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Units	Counts
Participants	OG000

Secondary

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).

Posted

Mean

Standard Deviation

mmHg

On days 1, 5 and 7 of the treatment period.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Units	Counts
Participants	OG000

Secondary

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).

Posted

Mean

Standard Deviation

bpm

On days 1, 5 and 7 of the treatment period.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Units	Counts
Participants	OG000

Secondary

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).

Posted

Mean

Standard Deviation

breaths/min

On days 1, 5 and 7 of the treatment period.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Units	Counts
Participants	OG000

Secondary

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.

Posted

Count of Participants

Participants

From day 1 to day 7 of the treatment period.

ID	Title	Description
OG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.
OG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MMH-407	Oral administration. Single dose: 1 tablet. First 24 hours of therapy: 1 tablet every 30 minutes for the first 2 hours, followed by 3 more tablets taken at regular intervals during the rest of the day. Days 2 to 5: 1 tablet 3 times daily. The product must not be taken with food, but in between meals or 15-30 minutes before meal; each tablet must be held in the mouth to let it dissolve completely before it can be swallowed. MMH-407: Oral administration.	0	118	0	118	9	118
EG001	Placebo	According to the scheme of receiving MMN-407 until the end of the study. Placebo: Oral administration.	0	122	1	122	9	118

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Epigastric pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 events2 affected118 at risk EG0010 events0 affected118 at risk
Diarrhea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected118 at risk
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected118 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected118 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected118 at risk
Purulent bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected118 at risk EG0011 events1 affected118 at risk
Acute nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected118 at risk
Acute tubootitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected118 at risk
Herpes simplex	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected118 at risk EG0011 events1 affected118 at risk
Increase in the percentage of basophils	Investigations	MedDRA	Systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected118 at risk
Increase in the percentage of eosinophils	Investigations	MedDRA	Systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected118 at risk
Exacerbation of bronchial asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected118 at risk
Intercostal neuralgia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected118 at risk
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected118 at risk
Edema of the lips and face	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected118 at risk
Worsening of the disease	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected118 at risk