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

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

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

Study Overview

• Status: Unknown
• Conditions: Influenza
• Intervention / Treatment: Biological: TCN-032; Biological: Placebo (saline)

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TCN-032; single-dose, administered intravenously	Biological: TCN-032
PLACEBO_COMPARATOR: Placebo (saline); single-dose, administered intravenously	Biological: Placebo (saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Theraclone Sciences, Inc.
• Investigators: Study Director: Eleanor L Ramos, MD, Theraclone Sciences, Inc.

Publications and helpful links

General Publications

• Ramos EL, Mitcham JL, Koller TD, Bonavia A, Usner DW, Balaratnam G, Fredlund P, Swiderek KM. Efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza. J Infect Dis. 2015 Apr 1;211(7):1038-44. doi: 10.1093/infdis/jiu539. Epub 2014 Oct 3.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2012
• Study Completion (ANTICIPATED): March 1, 2013

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: October 30, 2012
• First Posted (ESTIMATE): November 1, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 1, 2012
• Last Update Submitted That Met QC Criteria: October 30, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Influenza; monoclonal antibody
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: TCN-032-002