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Influenza Challenge Study of VIS410 in Healthy Volunteers

Phase 2
Completed
Conditions
Influenza
Interventions
Drug: Placebo
Registration Number
NCT02468115
Lead Sponsor
Visterra, Inc.
Brief Summary

A phase 2 a study to assess the safety profile and the effect of VIS410 in healthy subjects after inoculation with influenza A virus (H1N1).

Detailed Description

This is a phase 2a randomized, double-blind, placebo-controlled study to be conducted in healthy volunteers. The study is designed to compare an infusion of a single dose of VIS410 against placebo. Eligible volunteers will be admitted to the clinical center and will receive a single intranasal administration of influenza A (H1N1). One day (24h) after inoculation, subjects will receive a single administration of VIS410 or placebo. Subjects will be confined in the clinical center for 10 days after virus administration.

Assessment of safety will be determined from vital sign measurements, physical examinations, hematology, chemistry and urinalysis laboratory testing, 12-lead electrocardiograms (ECGs), pulmonary function, use of concomitant medications, and review of adverse events (AEs) should they occur. During confinement in the clinical center a symptom score card of influenza symptoms will be completed three times a day; nasopharyngeal swabs will be obtained three times a day and assayed for the presence of influenza virus and VIS410 concentration; serum samples will be assayed for VIS410 and the presence of cytokines. Upon release from the clinical center subjects will return for follow-up visits on days 14, 28 and either 56 or 84.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
46
Inclusion Criteria
  1. Male or female subjects of age 18-45 years, inclusive, at the time of informed consent.

  2. Women should fulfill one of the following criteria:

    • Post-menopausal; either amenorrhea ≥ 12 months or follicle stimulating hormone > 40 mIU/mL.
    • Surgically sterile; bilateral oophorectomy, hysterectomy, or tubal ligation.
    • Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception until the end of the study.
    • Must be sexually inactive by abstinence which is consistent with the preferred and usual lifestyle of the subject.
  3. Women of childbearing potential must have a negative pregnancy test at screening (serum) and on Day -2 (urine).

  4. Non-vasectomized (or vasectomized less than 6 months prior to dosing) male subjects must use an effective birth control method (see Inclusion Criterion 2).

  5. Seronegative for the challenge virus (HAI ≤ 10).

Exclusion Criteria
  1. Known or suspected intolerance or hypersensitivity to the investigational study drug or virus.
  2. Has an acute or chronic medical condition that would render the investigational study drug unsafe or would interfere with the evaluation of the responses.
  3. Subjects receiving medications that affect the immune system.
  4. Significant adulthood history of seasonal hay fever or a seasonal allergic rhinitis or perennial allergic rhinitis or chronic or nasal or sinus condition.
  5. Subjects who have received any vaccination within the last 3 months or influenza vaccine within the last 6 months.
  6. Subjects with a confirmed diagnosis of influenza A within the last 6 months prior to screening.
  7. Subjects with abnormal nasal structure (including septal deviation and nasal polyps), chronic sinusitis, or reason (i.e., intolerance) that complicates nasopharyngeal swabbing.
  8. Presence of lung disease, asthma, or chronic obstructive pulmonary disease.
  9. Has a history of alcohol or drug abuse.
  10. A positive HIV antibody screen, HBsAg, HBcAb or hepatitis C antibody screen.
  11. Cancer or treatment for cancer, within 3 years, excluding basal cell carcinoma of the skin, which is allowed.
  12. Presence of immunosuppression or any medical condition that may be associated with impaired immune responsiveness.
  13. Anticipated presence of a household contact with potential immunosuppression.
  14. History of Guillain-Barré syndrome.
  15. Current professional activity as a healthcare worker who will return to work within 2 weeks following challenge.
  16. Anticipated presence of a pregnant household contact, within 2 weeks following challenge.
  17. Women who are pregnant or breast-feeding, or consider becoming pregnant.
  18. Acute disease within 2 weeks prior to challenge.
  19. Elevated white blood cell count above 10.90 x 109/L or an absolute neutrophil count above 7.5 x 109/L.
  20. Current enrollment in any other investigational drug study or disease study or participation in an investigational drug study.
  21. Any other reasons for which the investigator considers the subject unfit for the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VIS410VIS410Single intravenous fixed dose of VIS410
PlaceboPlaceboSingle intravenous infusion of placebo
Primary Outcome Measures
NameTimeMethod
To assess the effect of VIS410 on the area under the curve of viral shedding over time.56-84 days

The viral AUC will be measured, qRT-PCR, and compared between treatment groups

To assess the safety profile of VIS41056-84 days

The proportion of subjects with post-infusion adverse events will be compared between treatment groups.

Secondary Outcome Measures
NameTimeMethod
Assess the pharmacokinetics of VIS410 in serum56-84 days

The following PK parameters will be calculated: Cmax, tmax, AUC, t1/2, Vd, Cl

Assess antibody to challenge strain28 days

The HAI antibody titer will be measured

Assess the effect of VIS410 on clinical symptoms10 days

The duration of symptoms will be compared between treatment groups

Assess the effects of VIS410 on viral shedding10 days

The peak viral load and time to cessation of shedding will be measured (qRT-PCR and TCID50)

Assess the immunogenicity of VIS41056-84 days

The development of anti-drug antibodies will be measured

Trial Locations

Locations (1)

SGS Life Sciences

🇧🇪

Antwerp, Belgium

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