Acute Respiratory Viral Infections, Influenza
Conditions
Brief summary
A multicenter double-blinded, randomized, placebo-controlled, parallel-group comparative Phase II clinical study to assess safety, tolerability, efficacy and optimal dose of XC221 vs. placebo in patients with uncomplicated influenza or other ARVI during a 3-day treatment. The primary objective of the study is to demonstrate the difference in time before the onset of a sustained improvement in clinical symptoms according to the Modified Jackson Scale for ARVI and to determine the optimal dose of XC221 in the treatment of influenza and other ARVI.
Detailed description
11 Russian centers were planned for participation in this study. The study consists of three periods: screening, treatment and follow-up. All eligible patients will be randomized into 3 groups (groups A, B and C) in a 1:1:1 ratio: Group A - XC221 100 mg daily (40 patients); Group B - XC221 200 mg daily (40 patients); Group C - Placebo (40 patients). During the treatment period (3 days), patients will receive XC221 / placebo daily on a background of standard symptomatic therapy. The follow-up period lasts for 11 days.
Interventions
DRUGXC221 100 mg
once daily during 3 days.
DRUGXC221 200 mg
once daily during 3 days.
DRUGPlacebo
once daily during 3 days.
Sponsors
PHARMENTERPRISES LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Blinding will carried out by using Placebo equivalent to XC221 tablets without active substance and the corresponding labeling of the study drug.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women aged 18 to 45 years (inclusively). 2. Clinically diagnosed influenza or ARVI. 3. Patient's body temperature ≥37.5ºС and at least 1 symptom from Modified Jackson Scale estimated more than 2 points. 4. Uncomplicated course of influenza or ARVI based on clinical estimations. 5. The first 36 hours from the beginning of symptoms of influenza or ARVI. 6. Women of reproductive age (who are not in menopause and who have not undergone surgical sterilization) and men who have sexual activity should use a reliable method of contraception (acceptable methods of contraception in this study are: intrauterine devices, oral contraceptives, contraceptive patch, long-acting injectable contraceptives, a double barrier method (condom and diaphragm with spermicide) throughout the study period. 7. Compliance with the treatment regimen, visits and laboratory examinations provided by the protocol. 8. Signed Informed Consent Form.
Exclusion criteria
1. Existence of complications of influenza or ARVI (including the presence / development of bacterial infection). 2. Hypersensitivity to excipients of the drug XC221 or placebo. 3. Antiviral medications in 7 days prior to screening (antiviral agents, interferons and interferon inducers, drugs that have immunomodulating action) or anti-infective agents of systemic or local action. 4. Severe infection with signs of cardiovascular insufficiency development and other manifestations of infectious-toxic shock, as well as with the presence of neuroinfection syndrome (encephalic and meningoencephalic reactions, polyradiculoneuritis, neuritis). 5. Signs of the development of viral pneumonia (the presence of two or more of the following symptoms): dyspnea, chest pain when coughing, systemic cyanosis, dullness of percussion sound with a symmetrical evaluation of the upper and lower sections of the lungs). 6. Infectious diseases during the last week before including into the study. 7. History of bronchial asthma. 8. History of increased convulsive activity. 9. Severe, decompensated or unstable somatic diseases (any diseases or conditions that are life-threatening or may worsen the patient's prognosis, and make him/her ineligible for the clinical study). 10. History of oncological diseases, HIV, tuberculosis. 11. Diabetes mellitus. 12. Drug or alcohol abuse. 13. Participation in any other clinical trial in the last 90 days. 14. Pregnancy or lactation. 15. Military or prison populations. 16. Impossibility or inability to comply with the study procedures. 17. A member of the investigator's family or other person interested in the results of the study. 18. Abnormal laboratory results, which, according to the study doctor, interfere with the patient's inclusion in the study. 19. History of renal insufficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained Improvement in Clinical Symptoms Based on Modified Jackson Scale for ARVI | From the time of randomization up to Day 14 | The time before the onset of sustained improvement in clinical symptoms according to the Modified Jackson Scale (no more than 1 point for each symptom), measured in hours from the moment of the first dose of the drug. Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Body Temperature Normalization | From the time of randomization assessed up to Day 14 | Time to body temperature normalization since treatment initiation, measured in hours (normalization is regarded as setting of body temperature below 37°C without elevation above these values) |
| Percentage of Patients With Complications | From the time of randomization up to Day 14 | The percentage of patients with complications of influenza/acute viral URI |
| The Area Under the Curve Modified Jackson Scale Score During 3-day Therapy | From randomization up to 3 days of treatment | Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. |
Countries
Russia
Participant flow
Recruitment details
Patients receiving both in- and outpatient treatment could be enrolled.
Pre-assignment details
A total of 121 patients were screened to participate in the trial; one patient was withdrawn at screening. 120 patients were randomly assigned into 3 groups.
Participants by arm
| Arm | Count |
|---|---|
| Group A XC221 100 mg orally.
1 tablet of XC221 100 mg +1 tablet of Placebo 100 mg (in total 2 tablets) once daily during 3 days of treatment period
XC221 100 mg: once daily during 3 days. | 40 |
| Group B XC221 200 mg orally. 2 tablets of XC221 100 mg once daily during 3 days of treatment period
XC221 200 mg: once daily during 3 days. | 40 |
| Group C Placebo orally. 2 tablets of Placebo 100 mg once daily during 3 days of treatment period
Placebo: once daily during 3 days. | 40 |
| Total | 120 |
Baseline characteristics
| Characteristic | Total | Group A | Group B | Group C |
|---|---|---|---|---|
| Age, Continuous | 31.1 years STANDARD_DEVIATION 7.5 | 30 years STANDARD_DEVIATION 7.3 | 31.1 years STANDARD_DEVIATION 7.1 | 32.2 years STANDARD_DEVIATION 8.1 |
| Presence of confirmed viral infection by PCR No viral infection confirmed by PCR | 42 Participants | 11 Participants | 13 Participants | 18 Participants |
| Presence of confirmed viral infection by PCR Viral infection confirmed by PCR | 78 Participants | 29 Participants | 27 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 119 Participants | 40 Participants | 39 Participants | 40 Participants |
| Region of Enrollment Russia | 120 participants | 40 participants | 40 participants | 40 participants |
| Sex: Female, Male Female | 72 Participants | 25 Participants | 24 Participants | 23 Participants |
| Sex: Female, Male Male | 48 Participants | 15 Participants | 16 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 16 / 40 | 13 / 40 | 14 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 0 / 40 |
Outcome results
Primary
Time to Sustained Improvement in Clinical Symptoms Based on Modified Jackson Scale for ARVI
The time before the onset of sustained improvement in clinical symptoms according to the Modified Jackson Scale (no more than 1 point for each symptom), measured in hours from the moment of the first dose of the drug. Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom.
Time frame: From the time of randomization up to Day 14
Population: Full Analysis Set (FAS) population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| XC221 100 mg | Time to Sustained Improvement in Clinical Symptoms Based on Modified Jackson Scale for ARVI | 57.38 hours |
| XC221 200 mg | Time to Sustained Improvement in Clinical Symptoms Based on Modified Jackson Scale for ARVI | 67.75 hours |
| Placebo | Time to Sustained Improvement in Clinical Symptoms Based on Modified Jackson Scale for ARVI | 69.64 hours |
p-value: 0.3541Gekhan-Wilcoxon test
Secondary
Percentage of Patients With Complications
The percentage of patients with complications of influenza/acute viral URI
Time frame: From the time of randomization up to Day 14
Population: FAS population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| XC221 100 mg | Percentage of Patients With Complications | No complications | 39 Participants |
| XC221 100 mg | Percentage of Patients With Complications | With complications | 1 Participants |
| XC221 200 mg | Percentage of Patients With Complications | No complications | 40 Participants |
| XC221 200 mg | Percentage of Patients With Complications | With complications | 0 Participants |
| Placebo | Percentage of Patients With Complications | No complications | 40 Participants |
| Placebo | Percentage of Patients With Complications | With complications | 0 Participants |
Secondary
The Area Under the Curve Modified Jackson Scale Score During 3-day Therapy
Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom.
Time frame: From randomization up to 3 days of treatment
Population: FAS population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XC221 100 mg | The Area Under the Curve Modified Jackson Scale Score During 3-day Therapy | 14.6 Ln(units_on_a_scale*sec) | Standard Deviation 0.4 |
| XC221 200 mg | The Area Under the Curve Modified Jackson Scale Score During 3-day Therapy | 14.6 Ln(units_on_a_scale*sec) | Standard Deviation 0.4 |
| Placebo | The Area Under the Curve Modified Jackson Scale Score During 3-day Therapy | 14.7 Ln(units_on_a_scale*sec) | Standard Deviation 0.4 |
p-value: 0.4551ANOVA
Secondary
Time to Body Temperature Normalization
Time to body temperature normalization since treatment initiation, measured in hours (normalization is regarded as setting of body temperature below 37°C without elevation above these values)
Time frame: From the time of randomization assessed up to Day 14
Population: FAS population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XC221 100 mg | Time to Body Temperature Normalization | 61.08 hours | Standard Deviation 52.85 |
| XC221 200 mg | Time to Body Temperature Normalization | 52.26 hours | Standard Deviation 34.08 |
| Placebo | Time to Body Temperature Normalization | 61.40 hours | Standard Deviation 38.06 |
p-value: 0.3597Gekhan-Wilcoxon test