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

Viral Respiratory Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04244084
• Other study ID #: MMH-407-001
• Status: Completed
• Phase: Phase 3
• Start date: October 8, 2019
• Est. completion date: April 9, 2020

Study information

• Verified date: October 2021
• Source: Materia Medica Holding
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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".

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: April 9, 2020
• Est. primary completion date: April 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Respiratory Tract Infections
• Viral Respiratory Infection
• Virus Diseases

Intervention

Drug:
• MMH-407
Oral use.
• Placebo
Oral use.

Locations

Country	Name	City	State
Russian Federation	Altai State Medical University, Department of Faculty Therapy with a course of immunology and allergology	Barnaul
Russian Federation	City Hospital #5	Barnaul
Russian Federation	Belgorod State National Research University, Hospital Therapy Department	Belgorod
Russian Federation	Road Clinical Hospital at Chelyabinsk station of JSC Russian Railways	Chelyabinsk
Russian Federation	City Clinical Hospital #9 of the Ministry of Health of the Udmurt Republic	Izhevsk
Russian Federation	Kazan State Medical University, Internal Medicine Department	Kazan
Russian Federation	Kazan State Medical University, Professorial clinic	Kazan
Russian Federation	Kuban State Medical University, Infectious Diseases and PhthisiopulmonologyDepartment	Krasnodar
Russian Federation	Central Clinical Hospital of the Russian Academy of Sciences	Moscow
Russian Federation	Moscow State Medical and Dental University named after A.I. Evdokimov, Pulmonology Laboratory	Moscow
Russian Federation	Road Clinical Hospital at the station Nizhny Novgorod of JSC Russian Railways	Nizhniy Novgorod
Russian Federation	City Clinical Hospital #10 of the Kanavinsky District of Nizhny Novgorod	Nizhny Novgorod
Russian Federation	Podolsk City Clinical Hospital # 3	Podolsk
Russian Federation	City Emergency Hospital Rostov-on-Don	Rostov-on-Don
Russian Federation	Ryazan State Medical University named after academician I.P. Pavlov, Department of Outpatient Therapy and Preventive Medicine	Ryazan
Russian Federation	City Polyclinic #25 of the Nevsky District	Saint Petersburg
Russian Federation	City Polyclinic #34	Saint Petersburg
Russian Federation	City Polyclinic #43	Saint Petersburg
Russian Federation	City Polyclinic #51	Saint Petersburg
Russian Federation	Medical Center "Reavita Med SPb"	Saint Petersburg
Russian Federation	Road Clinical Hospital of JSC Russian Railways	Saint Petersburg
Russian Federation	Vvedensky City Clinical Hospital	Saint Petersburg
Russian Federation	Samara City Hospital #4	Samara
Russian Federation	Scientific Medical Center for General Therapy and Pharmacology	Stavropol
Russian Federation	Bashkir State Medical University, Internal Medicine Department	Ufa
Russian Federation	Volgograd State Medical University	Volgograd

Sponsors (1)

Lead Sponsor	Collaborator
Materia Medica Holding

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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°? + 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 ?=0 points; 37.4-38.0 ?=1 point; 38.1-39.0 ?=2 points; =39.1 ?=3 points. The range of TSS was from "0" to "39".	14 days of observation.
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.	On days 1- 6 of the observation.
Secondary	Percentage of Patients With Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed)	ARVI's resolution criteria: temperature =37.3°? + 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 ?=0 points; 37.4-38.0 ?=1 point; 38.1-39.0 ?=2 points; =39.1 ?=3 points. The range of TSS was from "0" to "39".	On days 3, 4, 5 and 6 of observation.
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°? + 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 ?=0 points; 37.4-38.0 ?=1 point; 38.1-39.0 ?=2 points; =39.1 ?=3 points. The range of TSS was from "0" to "39".	14 days of observation.
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°? + 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 ?=0 points; 37.4-38.0 ?=1 point; 38.1-39.0 ?=2 points; =39.1 ?=3 points. The range of TSS was from "0" to "39".	On days 3, 4, 5 and 6 of observation.
Secondary	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.
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.	From day 4 to day 14 of the observation period.
Secondary	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.
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).	On days 1, 5 and 7 of the treatment period.
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).	On days 1, 5 and 7 of the treatment period.
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).	On days 1, 5 and 7 of the treatment period.
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.	From day 1 to day 7 of the treatment period.