Treatment of severe influenza A virus disease. MedDRA version: 14.1 Level: PT Classification code 10070215 Term: Influenza A virus test positive System Organ Class: 10022891 - Investigations MedDRA version: 14.1 Level: LLT Classification code 10022002 Term: Influenza A virus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: TCN-032
Product Code: TCN-032
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not applicable
Current Sponsor code: TCN-032
Concentration unit: mg/ml milligram(s)/millilit
Sponsors
THERACLONE SCIENCES, INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects will be considered eligible if they satisfy all of the following inclusion criteria: 1. Age 18 to 45 years, inclusive. 2. In good health with no history of major medical conditions from medical history, physical examination, and routine laboratory tests as determined by the Investigator by a screening evaluation no greater than 45 days prior to inoculum. 3. Body weight between 50 and 100 kg, inclusive (body mass index [BMI] >18 kg/m2 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Presence of significant acute or chronic, uncontrolled medical or psychiatric illness 2. History of autoimmune disease 3. History of adulthood asthma/chronic lung condition 4. History of recurrent lower respiratory tract infection or lower respiratory tract infection within 3 months of study 5. Positive for HIV, HBV or HCV 6. Subject is diabetic 7. Anatomic or neurologic abnormality impairing gag reflex 8. History of frequent epistaxis 9. Known IgA deficiency, immotile cilia syndrome or Kartageners syndrome 10. Nasal or sinus surgery within 6 months of study 11. Recent and/or recurrent history of autonomic dysfunction 12. Abnormal laboratory test deemed clinically significant 13. Abnormal ECG or abnormal spirometry deemed clinically relevant 14. Acute medical condition or significant past medical history of hepatic, renal, cardiovascular, pulmonary, gastrointestinal, hematological, locomotor, immunologic, ophthalmologic, metabolic, endocrine, or other diseases 15. Major surgery within 3 months of study 16. Evidence of drug abuse or positive urine Class A drug or alcohol screen 17. Venous access deemed inadequate 18. Subjects symptomatic with hay fever on admission into the unit for quarantine session or prior to viral inoculation will be excluded. 19. History of significant adverse reactions or allergies 20. History of allergy or intolerance to oseltamivir or zanamivir. 21. Health care workers 22. Presence of household member or close contact (for 2 weeks after discharge) who is at risk of contracting influenza 23. Intending to travel within the next 3 months 24. Employed or immediate relatives of those employed at RVL or Sponsor. 25. Receipt of blood or blood products or loss of >450 mL of blood within 3 months of study 26. Acute use of medication for rhinitis or nasal congestion within 1 week of study 27. Use of prescription drugs, herbal supplements, within 4 weeks of study at the discretion of the Investigator in conjunction with TCN 28. Chronic use of any medication for rhinitis/nasal congestion or chronic nasopharyngeal complaint 29. Receipt of any investigational drug within 3 months of study or prior participation in a clinical trial of influenza vaccine, experimental influenza viral challenge or other respiratory virus challenge within 1year prior study 30. Receipt of antiviral drugs within 1 month of study 31. Receipt of systemic glucocorticoids, immunoglobulins (Igs), other cytotoxic/immunosuppressive drugs, or systemic chemotherapy agent 32. Previous treatment with monoclonal antibodies 33. Presence of febrile illness/symptoms of viral respiratory infection within 2 weeks prior study 34. Physical examination or screening investigations which lead the Investigator(s) to consider the subject unfit for the study 35. Subjects, who in the opinion of their General Practitioner or the Chief Investigator or designee, should not participate in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the effect of TCN-032 compared to placebo in the development of influenza symptoms Grade 2 or higher, or pyrexia, from Day 1 to Day 7, after viral challenge.;Secondary Objective: Evaluate effect of TCN-032 vs. placebo in nasal virus AUC (viral culture, D1-7). Additional objectives- evaluation of: • Duration, time to peak, daily incidence of influenza symptoms =Grade 2, or pyrexia • Proportion (D1-7), duration, time to peak, daily incidence of components of primary objective: Upper & Lower respiratory & systemic influenza symptoms and pyrexia • Proportion (D1-7), duration, time to peak, daily incidence of any grade influenza symptoms, or pyrexia • Mucus weight (D1-7) • Peak value, time to peak, duration &daily incidence of virus shedding from nasal mucosa (viral culture) • AUC (D2-7), peak value, time to peak, duration & daily incidence of virus shedding from nasal mucosa (qPCR) • PK & immunogenicity of TCN-032 • Seroconversion and seroprotection to viral challenge strain • Change in HAI titre pre-challenge to D28 • Viral resistance to TCN-032 Evaluate safety of subjects who undergo viral challenge, with or without TCN-032 treatment.;Primary end point(s): The primary endpoint is the proportion of subjects who develop influenza symptoms Grade 2 or higher, or pyrexia, from Day 1 to Day 7, after influenza A viral challenge.;Timepoint(s) of evaluation of this end point: Day 1 to Day 7. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The main secondary endpoint is the total virus shedding (AUC) from the nasal mucosa, measured by viral culture, from Day 1 to Day 7, after influenza A viral challenge. Additional secondary endpoints include: • The duration, time to peak, and daily incidence of influenza symptoms Grade 2 or higher, or pyrexia • The proportion (from Day 1 to Day 7), duration, time to peak, and daily incidence of the components of the primary endpoint: o Upper respiratory symptoms o Lower respiratory symptoms o Systemic influenza symptoms o Pyrexia • The proportion (from Day 1 to Day 7), duration, time to peak, and daily incidence of any grade influenza symptoms, or pyrexia • Mucus weight (from Day 1 to Day 7) assessed by paper tissue weights • The peak value, time to peak, duration, and daily incidence of virus shedding from the nasal mucosa measured by viral culture • The AUC (Day 2 to Day 7), peak value, time to peak, duration, and daily incidence of virus shedding from the nasal mucosa measured by qPCR • PK and immunogenicity of TCN-032 • Incidence of seroconversion and seroprotection to viral challenge strain • Change in HAI titre pre-challenge to Day 28 • Proportion of subjects who develop viral resistance to TCN-032 (based on changes in TCN-032 binding, sequence changes in M2, ADCC susceptibility of infected cells) Safety endpoints: Incidence and severity of adverse events, incidence and severity of laboratory changes, changes in vital signs and clinical tests (ECG, spirometry);Timepoint(s) of evaluation of this end point: Day 1 to Day 28. | — |
Countries
United Kingdom
Contacts
Public ContactCharmaine O'Neil
Retroscreen Virology Limited
Outcome results
None listed