Clinical trial NCT01719874: Influenza Virus Challenge Study to Test Monoclonal Antibody TCN-032 as a Treatment for Influenza
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Influenza
Keywords: Influenza
monoclonal antibody
Lead sponsor: Theraclone Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2012-11-01
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: 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).
timeFrame: 7 days
Secondary outcomes:
measure: 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.
timeFrame: 7 days
measure: Pharmacokinetics (PK) and immunogenicity of TCN-032
timeFrame: up to 28 days after viral challenge
measure: Change in haemagglutination-inhibiting antibody (HAI) titre pre-challenge to Day 28.
timeFrame: 28 days after viral challenge
measure: Development of viral resistance to TCN-032
timeFrame: up to 9 days after viral challenge
measure: To evaluate the safety of subjects who undergo influenza A viral challenge, with or without treatment with TCN-032.
timeFrame: up to 28 days after viral challenge
measure: The duration of influenza symptoms or pyrexia
timeFrame: up to 10 days
measure: The time to peak of influenza symptoms or pyrexia
timeFrame: up to 10 days
measure: The daily incidence of influenza symptoms or pyrexia.
timeFrame: up to 10 days
measure: The proportion of the components of the primary objective: upper respiratory symptoms, lower respiratory symptoms, systemic influenza symptoms, pyrexia.
timeFrame: 7 days
measure: The duration of the components of the primary objective: upper respiratory symptoms, lower respiratory symptoms, systemic influenza symptoms, pyrexia.
timeFrame: 7 days
measure: The time to peak of the components of the primary objective: upper respiratory symptoms, lower respiratory symptoms, systemic influenza symptoms, pyrexia.
timeFrame: 7 days
measure: The daily incidence of the components of the primary objective: upper respiratory symptoms, lower respiratory symptoms, systemic influenza symptoms, pyrexia.
timeFrame: 7 days
measure: The proportion of any grade influenza symptoms, or pyrexia
timeFrame: 7 days
measure: The duration of any grade influenza symptoms, or pyrexia
timeFrame: 7 days
measure: The time to peak of any grade influenza symptoms, or pyrexia
timeFrame: 7 days
measure: The daily incidence of any grade influenza symptoms, or pyrexia
timeFrame: 7 days
measure: The peak value of virus shedding from the nasal mucosa measured by viral culture
timeFrame: up to 9 days
measure: The time to peak of virus shedding from the nasal mucosa measured by viral culture
timeFrame: up to 9 days
measure: The duration of virus shedding from the nasal mucosa measured by viral culture
timeFrame: up to 9 days
measure: The daily incidence of virus shedding from the nasal mucosa measured by viral culture
timeFrame: up to 9 days
measure: The AUC of virus shedding from the nasal mucosa measured by qPCR
timeFrame: 6 days
measure: The peak value of virus shedding from the nasal mucosa measured by qPCR
timeFrame: 6 days
measure: The time to peak of virus shedding from the nasal mucosa measured by qPCR
timeFrame: 6 days
measure: The duration of virus shedding from the nasal mucosa measured by qPCR
timeFrame: 6 days
measure: The daily incidence of virus shedding from the nasal mucosa measured by qPCR
timeFrame: 6 days
measure: Incidence of seroconversion to viral challenge strain
timeFrame: up to 28 days after viral challenge
measure: Incidence of seroprotection to viral challenge strain
timeFrame: up to 28 days after viral challenge
measure: Total tissue count and total mucus weight after viral inoculation
timeFrame: 7 days
Other outcomes:
Locations:
city: London
country: United Kingdom
Study officials:
affiliation: Theraclone Sciences, Inc.
name: Eleanor L Ramos, MD
role: STUDY_DIRECTOR
References:
citation: 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.