Influenza A (H1N1) infection MedDRA version: 18.0 Level: LLT Classification code 10063211 Term: Influenza A virus IgG System Organ Class: 100000004848
Conditions
Interventions
Product Code: VIS410
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: -
CAS Number: -
Current Sponsor code: VIS410
Other descriptive name: -
Concentration unit: mg/ml milligram(s)/milli
Sponsors
Visterra, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent prior to any procedures and be available for all study visits. 2. Male or female subjects of age 18-45 years, inclusive, at the time of informed consent. 3. Women should fulfill one of the following criteria: a. Post-menopausal; either amenorrhea = 12 months or follicle stimulating hormone > 40 mIU/mL. b. Surgically sterile; bilateral oophorectomy, hysterectomy, or tubal ligation. c. Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from screening until the end of the study. The following is considered adequate contraception: combination of an established form of hormonal contraception or an intrauterine device with a physical barrier method (condom, diaphragm or cervical/vault cap). The combination of 2 barrier methods, periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not considered acceptable methods of contraception. The use of contraception does not apply if the male partner has been vasectomized at least 6 months prior to dosing. d. Must be sexually inactive by abstinence which is consistent with the preferred and usual lifestyle of the subject. 4. Women of childbearing potential must have a negative pregnancy test at screening (serum) and on Day -2 (urine). 5. Non-vasectomized (or vasectomized less than 6 months prior to dosing) male subjects who have a female partner of childbearing potential must use an effective birth control method (see Inclusion Criterion 3) when having heterosexual intercourse, for the entire duration of the study. 6. Healthy, as determined by a satisfactory medical assessment with no clinically significant or relevant abnormalities in medical history, physical examination, vital signs, ECG, lab evaluations at screening, as assessed by the investigator. 7. Able to understand and comply with planned study procedures and restrictions. 8. Seronegative for the challenge virus (HAI = 10) not more than 4 weeks before dosing. 9. Non- smoker and non-habitual smoker (habitual smokers are persons who smoke more than 4 cigarettes or other tobacco products on a weekly basis) and agree to not use tobacco products during confinement. Note: In case of an out-of-range clinical laboratory test, vital sign, or ECG value that will determine a subject’s eligibility, or in case of a positive drug screen, a retest can be done. Results of this retest must be available prior to viral inoculation (Day 1) and if abnormal, must be nonclinically significant for a subject to be enrolled in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known or suspected intolerance or hypersensitivity to the investigational study drug or virus, or closely related compounds (e.g., other monoclonal antibodies) or any of the stated ingredients, including egg allergies or any moderate to severe allergic disorder, or any suspected intolerance or hypersensitivity to the possible pretreatment drugs (diphenhydramine, ranitidine, montelukast, or paracetamol for Part 1 only; diphenhydramine, ranitidine, montelukast, or ibuprofen for Part 2 only; pretreatments of Part 3 are selected based on Part 2). 2. Has an acute or chronic medical condition that, in the opinion of the investigator, would render the investigational study drug unsafe or would interfere with the evaluation of the responses, including but not limited to, cardiovascular, respiratory, autoimmune, or immune suppression conditions. 3. Subjects receiving medications that affect the immune system including systemic steroids and subjects on chronic medications where the dose has not been stable for at least 3 months. The use any of concomitant therapies is prohibited during the study, except for contraception and paracetamol (as per license). 4. Significant adulthood history of seasonal hay fever or a seasonal allergic rhinitis or perennial allergic rhinitis or chronic or nasal or sinus condition such as chronic sinusitis. 5. Diastolic blood pressure (DBP) 90 mmHg, a systolic BP (SBP) 150 mmHg, a pulse 100 bpm after resting in supine position for 5 minutes. 6. Subjects who have received any vaccination within the last 3 months or influenza vaccine within the last 6 months or who anticipate receiving this during the study. 7. Subjects with a confirmed diagnosis of influenza A within the last 6 months prior to screening. 8. Has a history of receiving monoclonal antibody, immunoglobulin or other blood products within 3 months prior to enrolment in this study or planned administration during the study period. 9. Donation (500 mL) of blood or blood products (e.g. plasma, platelets) within 3 months prior to or intention to donate blood during the study. 10. Subjects with abnormal nasal structure (including septal deviation and nasal polyps), chronic sinusitis, or reason (i.e., intolerance) that in the opinion of the investigator complicates nasopharyngeal swabbing. 11. Presence of lung disease, asthma, or chronic obstructive pulmonary disease. 12. Has a history of alcohol or drug abuse in the last year or has a positive screen for drugs of abuse (amphetamines, benzodiazepines, cocaine, methadone, or opiates) or alcohol at screening or Day -2. 13. A positive human immunodeficiency virus (HIV) antibody screen, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody screen. 14. Cancer or treatment for cancer, within 3 years, excluding basal cell carcinoma of the skin, which is allowed. 15. Presence of immunosuppression or any medical condition that may be associated with impaired immune responsiveness, including but not limited to, diabetes mellitus and inflammatory bowel disease. 16. Anticipated presence of a household contact with potential immunosuppression (in the opinion of the investigator), either as a result of disease and/or therapy. 17. History of Guillain-Barré syndrome. 18. Current professional activity as a healthcare worker who will return to work within 2 weeks following challenge. 19. Anticipated presence of a pregnant household contac
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are to assess the safety profile of VIS410 (Part 1, 2 and 3) and the effect of VIS410 on the area under the curve of viral shedding over time (viral AUC) in healthy subjects after viral inoculation with influenza A (H1N1) (Part 1 only).;Secondary Objective: Secondary objectives are to: - Assess the effects of VIS410 on viral shedding. - Assess the pharmacokinetics of VIS410 in serum. - Assess the immunogenicity of VIS410. - Assess the effect of VIS410 on clinical symptoms. - Assess antibody to challenge strain. - Assess the effect of different pretreatments on the safety and tolerability of VIS410 in healthy subjects after viral inoculation with influenza A (H1N1).;Primary end point(s): - The proportion of subjects with post-infusion AEs including hypersensitivity reaction, anaphylactic reaction and other AEs occurring within 1 h of the completion of dosing; - The proportion of subjects with AEs and SAEs; - The difference between VIS410 and placebo treatment groups in viral AUC by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from nasopharyngeal swabs (Part 1 only).;Timepoint(s) of evaluation of this end point: - Within 1 h of the completion of the dosing - Throughout duration of trial - At the end of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The difference between VIS410 and placebo treatment groups in viral AUC (tissue culture infective dose that induces a pathological change in 50% of cell culture isolates [TCID50]) from nasopharyngeal swabs (Part 1 only); - Peak viral load and time to cessation of viral shedding (qRT-PCR and TCID50) (Part 1 alone and pooled data [Part 1 + Part 2]); - VIS410 PK parameters (Cmax, tmax, AUC extrapolated to infinity [AUC0-8], AUC calculated between time of administration and time t [AUC0-t], t1/2, volume of distribution (Vd), clearance [CL]) in serum; - Titer of serum antibody to challenge strain; - Titer of anti-VIS410 antibody positive samples; - The incidence, severity and duration of signs and symptoms of influenza-like illness as reported by the subjects and assessed by the investigator after virus challenge followed by a single IV dose of VIS410. - The incidence, severity and duration of gastrointestinal signs and symptoms as reported by the subjects and assessed by the investigator after virus challenge followed by administration of different pre-treatments prior to a single IV dose of VIS410.;Timepoint(s) of evaluation of this end point: - At the end of the trial - At the end of the trial - At the end of the trial - At the end of the trial - At the end of the trial - At the end of the trial | — |
Countries
Belgium
Contacts
Public Contact-
Visterra, Inc.
Outcome results
None listed