Study to Assess Efficacy and Safety of XC221 in the Treatment of Influenza and Other Acute Respiratory Viral Infections

Phase 2

Completed

• Conditions: Acute Respiratory Viral Infections; Influenza
• Interventions: Drug: XC221 100 mg; Drug: XC221 200 mg; Drug: Placebo

• Registration Number: NCT03455491
• Lead Sponsor: PHARMENTERPRISES LLC

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.

Study Timeline

• Study Start: 2018-02-12
• Study First Submitted: 2018-02-28
• Study First Submitted QC: 2018-02-28
• Study First Posted: 2018-03-06
• Primary Completion: 2018-06-28
• Study Completion: 2018-06-28
• Results First Submitted: 2019-02-18
• Status Verified: 2019-10
• Results First Submitted QC: 2019-10-14
• Last Update Submitted: 2019-10-14
• Results First Posted: 2019-11-04
• Last Update Posted: 2019-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
XC221 100 mg	XC221 100 mg	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 200 mg	XC221 200 mg	XC221 200 mg orally. 2 tablets of XC221 100 mg once daily during 3 days of treatment period
Placebo	Placebo	Placebo orally. 2 tablets of Placebo 100 mg once daily during 3 days of treatment period

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (11)

The Consulting and Diagnostic Center with out-patient help of the Administration of the President of the Russian Federation; 🇷🇺 Saint Petersburg, Russian Federation

Research Institute of Influenza; 🇷🇺 Saint Petersburg, Russian Federation

City Clinical Hospital №40 of Kurortny District; 🇷🇺 Saint Petersburg, Russian Federation

Ryazan State Medical University n.a. Pavlov; 🇷🇺 Ryazan', Russian Federation

Kuban State Medical University; 🇷🇺 Krasnodar, Russian Federation

City Clinical Hospital №9; 🇷🇺 Izhevsk, Russian Federation

City Clinical Hospital №1 n.a. Semashko; 🇷🇺 Rostov-on-Don, Russian Federation

The Center for Prevention and Fight about AIDS and Infectious Diseases; 🇷🇺 Saint Petersburg, Russian Federation

Mordovia State Medical University n.a. N.P.Ogarev, Clinical site - Republic Infectious Clinical Hospital; 🇷🇺 Saransk, Russian Federation

Сlinical Hospital №3; 🇷🇺 Yaroslavl, Russian Federation

Volgograd State Medical University, Clinical site - Infectious Regional Clinical Hospital № 1; 🇷🇺 Volgograd, Russian Federation