Efficacy and Safety of Norketotifen in Uncomplicated Influenza-like Illness

Study Overview
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Brief Summary
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This is a Phase 2b, multi-center, double-blind, randomized, placebo-controlled, parallel-group study of NKT versus placebo in otherwise healthy adults presenting with acute uncomplicated ILI due to influenza or other respiratory viruses in a community setting.

Official Title
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A Phase 2b Double-blind, Randomized, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of Norketotifen (NKT) in the Treatment of Acute Uncomplicated Influenza-like Illness (ILI)

Conditions
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Influenza, Influenza -Like Illness

Intervention / Treatment
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* Drug: Norketotifen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand the study and comply with all study procedures, and willing to provide written informed consent prior to the pre-dose examinations Symptoms of ILI including all of the following: Fever ≥38º Celsius (oral) At least one of the following general systemic symptoms associated with ILI are present with a severity of moderate or greater: headache, feverishness or chills, muscle or joint pain, fatigue At least one of the following respiratory symptoms associated with ILI are present with a severity of moderate or greater: cough, sore throat, nasal congestion Total symptom severity score (sum of the scores of all 7 individual symptoms) of ≥11 in the predose examinations The time interval between the onset of symptoms and the predose examinations is ≤48 hours. Females of childbearing potential and males agree to use an appropriate method of contraception as detailed in the protocol Exclusion Criteria: Known or suspected infection with Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) or Coronavirus Disease 2019 (COVID-19) illness Female subjects who are pregnant, 2 weeks post-partum, or breastfeeding Severe ILI requiring inpatient treatment Any of the following risk factors (according to the CDC's list of People at High Risk for Developing Serious Flu-Related Complications): Extreme obesity (body mass index ≥40 kg/m^2) Residents of nursing homes or other long-term care facilities American Indians and Alaska natives Asthma Chronic lung disease (such as chronic obstructive pulmonary disease or cystic fibrosis) Neurological and neurodevelopmental conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury) Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease) Blood disorders (such as sickle cell disease) Endocrine disorders (such as diabetes mellitus) Kidney disorders Liver disorders Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders) Compromised immune system due to disease or medication (such as subjects with human immunodeficiency virus or cancer, or those on chronic steroids) Presence of any severe or uncontrolled medical or psychiatric illness History of or current autoimmune disease History of recurrent lower respiratory tract infection Any concurrent infection requiring systemic antimicrobial and/or antiviral therapy Any clinically significant electrocardiogram (ECG) test Received baloxavir, oseltamivir, peramivir, zanamivir, rimantadine, or amantadine within 30 days prior to the predose examinations Received an investigational monoclonal antibody for a viral disease in the last year prior to the predose examinations Received ketotifen fumarate, cromolyn sodium, or nedocromil sodium by any route of administration within 30 days prior to the predose examinations Exposure to an investigational drug within 30 days prior to the predose examinations History of allergic reaction to ketotifen Any prior exposure to norketotifen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Norketotifen<br>Norketotifen oral capsules, twice daily for 7 days | Drug: Norketotifen<br>* Oral capsule<br>|
| Placebo Comparator: Placebo<br>Placebo oral capsules, twice daily for 7 days | Drug: Placebo<br>* Oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to alleviation of symptoms | Time to alleviation of the symptoms of ILI (headache, feverishness/chills, muscle/joint pain, fatigue, cough, sore throat, nasal congestion) | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to resolution of fever (body temperature equal to or less than 37ºC) |  | 14 days | 
| Proportion of subjects whose symptoms have been alleviated at each time point through Day 14 |  | 14 days | 
| Change from baseline in composite symptom score at each time point through Day 14 |  | 14 days | 
| Body temperature at each time point through Day 14 |  | 14 days | 
| Time to alleviation of individual symptoms (headache, feverishness/chills, muscle/joint pain, fatigue, cough, sore throat, nasal congestion) |  | 14 days | 
| Time to resumption of normal activity |  | 14 days | 
| Use of rescue medication (acetaminophen) |  | 14 days | 
| Time to alleviation of symptoms by confirmed viral pathogen (influenza vs non influenza) |  | 14 days | 
| Time to resolution of fever by confirmed viral pathogen (influenza vs non influenza) |  | 14 days |