Influenza Virus Challenge Study to Test Monoclonal Antibody TCN-032 as a Treatment for Influenza

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety and efficacy of TCN-032 given to healthy adult volunteers that have been inoculated with the influenza A virus

Official Title
-----------------
A Phase 2a, Double-Blind, Placebo-Controlled Study TCN 032 (Human Monoclonal Antibody Directed Against the M2 Protein of Influenza A Virus) in Subjects Challenged With H3N2 Influenza A Virus

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: TCN-032
* Biological: Placebo (saline)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 to 45 years, inclusive. In good health with no history of major medical conditions Female subjects must not be pregnant or nursing Have not been vaccinated for influenza virus since 2006 Serosusceptible to the challenge virus Non-smoker or current smoker willing/able to desist Exclusion Criteria: Presence of any significant acute or chronic, uncontrolled medical or psychiatric illness History or evidence of autoimmune disease Any history during adulthood of asthma, history of COPD, pulmonary hypertension, reactive airway disease, any chronic lung condition of any etiology), or any use of a bronchodilator or other asthma medication within adulthood History or clinical evidence of recurrent lower respiratory tract infection Positive human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) antibody screen Subject is diabetic History of frequent epistaxis (nose bleeds) Any nasal or sinus surgery within 6 months of the screening visit Recent and/or recurrent history of autonomic dysfunction (fainting, palpitations, etc.) Any laboratory test, ECG or spirometry which is abnormal and which is deemed by the Investigator(s) to be clinically significant. Any acute medical condition or significant past medical history of hepatic, renal, cardiovascular, pulmonary, gastrointestinal, haematological, locomotor, immunologic, ophthalmologic, metabolic, endocrine, or other diseases Major surgery within 3 months prior to screening visit Evidence of drug of abuse or positive urine Class A drug or alcohol screen prior to admission Subjects symptomatic with hay fever Subjects with a history of significant adverse reactions/allergies History of allergy or intolerance to oseltamivir or zanamivir. Health care workers (including doctors, nurses, medical students, and allied healthcare professionals) anticipated to have patient contact within 2 weeks of viral challenge.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCN-032<br>single-dose, administered intravenously | Biological: TCN-032<br> <br> |
| Placebo Comparator: Placebo (saline)<br>single-dose, administered intravenously | Biological: Placebo (saline)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective is to evaluate the effect of TCN-032 compared to placebo in the development of clinical signs and symptoms of influenza (including upper respiratory, lower respiratory, systemic and fever). |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main secondary objective is to evaluate the effect of TCN-032 compared to placebo in total virus shedding (measured by area under the curve [AUC]) from the nasal mucosa, measured by viral culture. |  | 7 days | 
| Pharmacokinetics (PK) and immunogenicity of TCN-032 |  | up to 28 days after viral challenge | 
| Change in haemagglutination-inhibiting antibody (HAI) titre pre-challenge to Day 28. |  | 28 days after viral challenge | 
| Development of viral resistance to TCN-032 |  | up to 9 days after viral challenge | 
| To evaluate the safety of subjects who undergo influenza A viral challenge, with or without treatment with TCN-032. |  | up to 28 days after viral challenge | 
| The duration of influenza symptoms or pyrexia |  | up to 10 days | 
| The time to peak of influenza symptoms or pyrexia |  | up to 10 days | 
| The daily incidence of influenza symptoms or pyrexia. |  | up to 10 days | 
| The proportion of the components of the primary objective: upper respiratory symptoms, lower respiratory symptoms, systemic influenza symptoms, pyrexia. |  | 7 days | 
| The duration of the components of the primary objective: upper respiratory symptoms, lower respiratory symptoms, systemic influenza symptoms, pyrexia. |  | 7 days | 
| The time to peak of the components of the primary objective: upper respiratory symptoms, lower respiratory symptoms, systemic influenza symptoms, pyrexia. |  | 7 days | 
| The daily incidence of the components of the primary objective: upper respiratory symptoms, lower respiratory symptoms, systemic influenza symptoms, pyrexia. |  | 7 days | 
| The proportion of any grade influenza symptoms, or pyrexia |  | 7 days | 
| The duration of any grade influenza symptoms, or pyrexia |  | 7 days | 
| The time to peak of any grade influenza symptoms, or pyrexia |  | 7 days | 
| The daily incidence of any grade influenza symptoms, or pyrexia |  | 7 days | 
| The peak value of virus shedding from the nasal mucosa measured by viral culture |  | up to 9 days | 
| The time to peak of virus shedding from the nasal mucosa measured by viral culture |  | up to 9 days | 
| The duration of virus shedding from the nasal mucosa measured by viral culture |  | up to 9 days | 
| The daily incidence of virus shedding from the nasal mucosa measured by viral culture |  | up to 9 days | 
| The AUC of virus shedding from the nasal mucosa measured by qPCR |  | 6 days | 
| The peak value of virus shedding from the nasal mucosa measured by qPCR |  | 6 days | 
| The time to peak of virus shedding from the nasal mucosa measured by qPCR |  | 6 days | 
| The duration of virus shedding from the nasal mucosa measured by qPCR |  | 6 days | 
| The daily incidence of virus shedding from the nasal mucosa measured by qPCR |  | 6 days | 
| Incidence of seroconversion to viral challenge strain |  | up to 28 days after viral challenge | 
| Incidence of seroprotection to viral challenge strain |  | up to 28 days after viral challenge | 
| Total tissue count and total mucus weight after viral inoculation |  | 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
monoclonal antibody, Influenza