Phase II Clinical Study to Evaluate Safety and Efficacy of Azelastine 0.1% Nasal Spray in Non-hospitalized Patients with Mild COVID-19 Infection
Scientific Title of Study
A Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-Group, Multicentric, Phase II Clinical Study to Evaluate Safety and Efficacy of Azelastine 0.1% Nasal Spray in Non-hospitalized Patients with Mild COVID-19 Infection
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
URSA-CARVIN-II-001 Version No.: 3.0, Date: 19.05.2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Rajesh Jain
Designation
Head of Operations, India and Global Lead Clinical Services Solutions
Affiliation
PharmaLex India Pvt. Ltd.
Address
PharmaLex India Pvt. Ltd.
3rd Floor, Plot No. 1 and 2, Tower A, Maple Corporate Park,
Sector 125, Noida, Uttar Pradesh, India 201301
Gautam Buddha Nagar UTTAR PRADESH 201301 India
Phone
9769127112
Fax
Email
Rajesh.Jain@pharmalex.com
Details of Contact Person Scientific Query
Name
Dr Rajesh Jain
Designation
Head of Operations, India and Global Lead Clinical Services Solutions
Affiliation
PharmaLex India Pvt. Ltd.
Address
PharmaLex India Pvt. Ltd.
3rd Floor, Plot No. 1 and 2, Tower A, Maple Corporate Park, Sector 125, Noida, Uttar Pradesh 201301.
Gautam Buddha Nagar UTTAR PRADESH 201301 India
Phone
9769127112
Fax
Email
Rajesh.Jain@pharmalex.com
Details of Contact Person Public Query
Name
Dr Rajesh Jain
Designation
Head of Operations, India and Global Lead Clinical Services Solutions
Affiliation
PharmaLex India Pvt. Ltd.
Address
PharmaLex India Pvt. Ltd.
3rd Floor, Plot No. 1 and 2, Tower A, Maple Corporate Park, Sector 125, Noida, Uttar Pradesh 201301
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Azelastine 0.1% nasal spray
1 mg/mL azelastine hydrochloride (0.1% Azelastine HCl)
one puff of study treatment
(i.e., Azelastine 0.1% nasal spray) to be self-administered by the patient in each nostril
5 times a day (preferentially at intervals of about 3 hours during the day). Daily
administrations on Days 2-10 should not be less than 3 applications per nostril. On
Day 1 (day of inclusion of the patient), at least two applications of the nasal spray per
nostril should be performed. On Day 11 (last day of treatment), at least 1 application
should be performed before the investigator’s/designee visit.
Comparator Agent
Placebo
The placebo will be identical in appearance to the IMP
one puff of Placebo to be self-administered by the patient in each nostril
5 times a day (preferentially at intervals of about 3 hours during the day). Daily
administrations on Days 2-10 should not be less than 3 applications per nostril. On
Day 1 (day of inclusion of the patient), at least two applications of the nasal spray per nostril should be performed. On Day 11 (last day of treatment), at least 1 application should be performed before the investigator’s/designee visit.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
90.00 Year(s)
Gender
Both
Details
Patients must meet all the following inclusion criteria in order to participate in this study:
1. Patients or legally accepted representative (LAR) provides informed consent prior to initiation of any study procedures.
2. Patients or LAR understands and agrees to comply with planned study procedures.
3. Male or female patients ≥18 years of age at the time of enrollment.
4. Patients with positive Rapid Antigen Test for SARS-CoV-2.
5. Willing to provide nasopharyngeal swabs
6. For females: non-pregnant, non-lactating with adequate contraception until Day 11, or females unable to bear children (i.e., tubal ligation, hysterectomy, or post-menopausal (defined as a minimum of one year since the last menstrual period).
ExclusionCriteria
Details
Patient’s meeting any of the following criteria are not eligible for the study:
1. Having any contraindication for the use of azelastine (including hypersensitivity to the active substance or other ingredients).
2. Patients requiring hospitalization (social admission will be an exception wherein the patient could have mild symptoms requiring quarantine, but no facility is available for the same and thereby hospitalization).
3. Patients with moderate (peripheral capillary oxygen saturation [SpO2] <93%) or severe COVID-19 disease (SpO2 <90%) based on MoH FW guidelines, Revised on 23-Sep-2021.
4. Any concurrent antihistamine therapy (systemic as well).
5. Any concurrent nasal spray or any nasalia including nasal lavage fluid.
6. Inability to administer the nasal spray.
7. Patients with nasal structure abnormalities, including nasal ulceration, nasal mucosal erosion, large nasal polyps and marked septal deviations that significantly interfere with nasal airflow.
8. Patients with alcohol or drug dependence.
9. Patients receiving any concurrent anti-COVID therapy (including off-label use).
10. Where, in the opinion of the investigator, participation in this study will not be in the best interest of the patient or any other circumstances that prevent the patient from participating in the study safely
11. Specific vulnerable patients: patients who are detained or committed to institutions by law court or by legal authorities, such as psychiatric wards, prisons, or other state institutions.
12. Patients with a history of psychiatric illness.
13. Simultaneous participation in other clinical studies or previous participation within 30 days before inclusion.
14. Being in any relationship or dependence with the Sponsor, Contract Research Organization (CRO), and/or Investigator.
Note: If the RT-PCR test is negative for a patient, that patient will be taken off from the study.
Method of Generating Random Sequence
Permuted block randomization, variable
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
The primary endpoints of the study are:
• Rate of COVID-19 related hospitalization in patients with SARS-CoV-2 infection in the treatment group as compared to control group
• Decrease in mean virus load in individual patients estimated via quantitative RT-PCR by using nasopharyngeal swabs
The primary endpoints of the study are:
Rate of COVID-19 related hospitalization in patients with
SARS-CoV-2 infection in the treatment group as compared to
control group (up to Day 11)
Decrease in mean virus load in individual patients estimated via
quantitative RT-PCR by using nasopharyngeal swabs (from
Baseline [Day 1] to Day 3, Day 6, and Day 11).
Secondary Outcome
Outcome
TimePoints
The secondary outcome of the study are:
• Safety assessment (occurrence of adverse events [AEs]) (post-randomization till Day 30). Safety assessments of patients who report COVID symptoms of mild COVID-19 on Day 30 will also be taken on Day 60 (±1 day) through a telephonic call
• Proportion of patients demonstrating a 10-fold decrease in virus load of SARS-CoV-2
• Ct values
o The Ct value shall be plotted on a graph for all patients.
o The change in Ct value will be calculated over the treatment period
o Rate of decline of Ct values
o Time to Cure
• Change in symptom severity (symptom score based on MoH FW checklist)
• The change in patient status using a 11-category ordinal score as proposed by the World Health Organization (WHO)
• The change in patient status by measurement of temperature (fever) and oxygen saturation of the blood by use of a finger pulse oxymeter
• Proportion of subjects with negative conversion of SARS-CoV 2 RT PCR
Safety assessment (post- randomization till Day 30). Safety assessments of patients on Day 30 will be taken on Day 60 (±1 day) through a telephonic call. Proportion of patients demonstrating 10-fold decrease in virus load , Ct values and change in Ct value will be calculated over treatment period. Change in symptom severity, change in patient status using 11- category ordinal score, measurement of temperature (fever) and SpO2 (from Baseline [Day 1] to Day 3, Day 6, and Day 11)
Target Sample Size
Total Sample Size="290" Sample Size from India="290" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="294"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicentric, Phase II clinical study which will be conducted in patients with mild COVID-19 infection not requiring hospitalization at time of screening for the study, with or without co-morbidities, to evaluate the safety and efficacy of Azelastine 0.1% nasal spray. The study is planned to be conducted at multiple sites in India.
The study will have a total of 6 visits. Visit 1/screening visit can be a hospital OPD/home/quarantine center-based visit. All other subsequent visits will be home/quarantine facility visits which will be done by the site personnel for all study-related activities, as the patients will be quarantined. In case, the study personnel will not be able to visit the home/quarantine facility due to COVID-19 restrictions or any other unavoidable reasons, the study-related procedures will be performed via tele-video conferencing