Study of an Investigational Monoclonal Antibody, VIS410, in Subjects With Uncomplicated Influenza A

Study Overview
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Brief Summary
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This is a Phase 2a randomized, double-blind, placebo-controlled study designed to assess the safety and tolerability of an investigational monoclonal antibody, VIS410, in subjects with uncomplicated influenza.

Detailed Description
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Subjects will be admitted to an infusion unit for drug administration and observation following infusion. The study is designed to compare an infusion of a single high or low IV dose of VIS410 against placebo. Subjects will be followed for 100 (±7 days).

Official Title
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A Phase 2a Double-blind, Placebo-controlled Study to Assess the Safety and Tolerability of a Single Intravenous Dose of an Investigational Monoclonal Antibody With Code Name VIS410 in Subjects With Uncomplicated Influenza A Infection

Conditions
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Influenza

Intervention / Treatment
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* Drug: VIS410 low dose
* Drug: VIS410 high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged ≥18 years and ˂65 years Women should fulfill one of the following criteria: Post-menopausal; either amenorrhea ≥12 months or follicle stimulating hormone >40 mIU/mL (milli-international units/milliliter) as documented in their medical history Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from screening until 60 days post infusion 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 when having heterosexual intercourse, from screening until 60 days post infusion Test positive for influenza A by Rapid Antigen Test performed with a commercially available test on an adequate nasopharyngeal specimen in accordance with the manufacturer's instructions Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms) of moderate to severe intensity, or presence of at least one constitutional symptom (myalgia [aches and pains], headache, feverishness, or fatigue) of moderate to severe intensity Onset of symptoms (time when the temperature was first measured as elevated [temperature of ≥100.4°F or ≥38°C], OR the time when the subject experienced at least one respiratory symptom or at least one constitutional symptom) no more than 72 hours before the start of infusion Exclusion Criteria: Use of NSAIDs or antihistamines within 6 hours of study drug dosing with the exception of those used as part of the pretreatment regimen History of intolerance or allergic response to monoclonal antibodies and/or pretreatment medications (diphenhydramine, ibuprofen and acetylsalicylic acid) Subject weight less than (<) 45 kg Subjects with clinical history that would lead to increased risk of influenza complications including but not limited to clinically significant cardiac disease, moderate to severe asthma, or other moderate to severe chronic obstructive pulmonary disease, metabolic syndrome including moderate to severe diabetes or active tuberculosis History of chronic GI disease, including bleeding, ulceration, Irritable Bowel Syndrome, systemic mastocytosis or chronic diarrhea Women who are pregnant, breast-feeding, or considering becoming pregnant Patients with hypoxemia requiring oxygen support Clinical evidence of worsening of any chronic medical condition (temporally associated with the onset of symptoms of influenza) which, in the Investigator's opinion, indicates that such finding(s) could represent complications of influenza Presence of immunocompromised status due to chronic illness, previous organ transplant, or use of immunosuppressive medical therapy including systemic steroids Presence of known Acquired Immune Deficiency Syndrome-defining illness, chronic hepatitis B or hepatitis C Receipt of any dose of antiviral therapy such as, but not limited to, rimantadine, amantadine, peramivir, zanamivir, laninamivir or oseltamivir in the 7 days prior to screening Enrollment in any other investigational drug or device study, any disease or vaccine study within 30 days prior to Day 1 or within 5 half-lives of the investigational compound, whichever is longer Subjects unable to take oral predose medication Known or suspected alcohol or drug abuse, that is, abuse of a level that would compromise the safety or cooperation of the subject in the opinion of the Investigator Subjects on chronic medications where the dose has not been stable for at least 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIS410 low dose<br>Single intravenous fixed low dose of VIS410 | Drug: VIS410 low dose<br>* Single intravenous fixed low dose of VIS410<br>|
| Experimental: VIS410 high dose<br>Single intravenous fixed high dose of VIS410 | Drug: VIS410 high dose<br>* Single intravenous fixed high dose of VIS410<br>|
| Placebo Comparator: Placebo<br>Single intravenous placebo infusion | Drug: Placebo<br>* Single intravenous infusion of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Safety and Tolerability of a Single IV Dose of VIS410 in Participants With Uncomplicated Influenza Infection | The percentage of participants with adverse events (AEs) and serious adverse events (SAEs) following administration of a single dose of IV VIS410. | 100 days | 
| Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest | Percentage of participants experiencing any TEAE, TEAEs considered related to study treatment and the number of participants experiencing adverse events of special interest (AESI). A TEAE is defined as an adverse event that starts on or after the date of study drug IV infusion. AESIs included hypersensitivity reaction, anaphylactic reaction, or injection site adverse event. | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410 | The Influenza Patient Reported Outcome (FluPRO) questionnaire is a 32-question instrument that assesses the occurrence and intensity of influenza associated symptoms (scale of 0 to 4, with 0 representing no symptoms) over 24 hours (lower scores indicate better outcomes). FluPRO data were recorded by subjects at Baseline (Day 1), then daily thereafter through Day 10. These data were summarized at each visit by treatment group. The data below show the percent change in mean total symptom scores over time by treatment arm. | 10 days | 
| Hospitalization for Influenza-related Complications | Number of participants requiring hospitalization for influenza-related complications | 100 days | 
| Duration of Hospitalization for Complications of Influenza | Duration of hospitalization for participants with at least 1 complication of influenza. There were no participants hospitalized for complications of influenza. | 100 days | 
| Count of Participants With Complications of Influenza | Count of participants with at least 1 complication of influenza | 100 days | 
| Influenza A Relapse/Reinfection | Number of participants with influenza A relapse/reinfection | 100 days | 
| VIS410 Maximum Plasma Concentration | The maximum observed concentration of VIS410 in serum (Cmax). | 1, 3, 5, 7, 14, 28, 56, 100 days | 
| Pharmacokinetics of VIS410 Concentration in Serum | Time corresponding to the maximum serum concentration of VIS410. | 1, 3, 5, 7, 14, 28, 56, 100 days | 
| VIS410 Plasma Concentration ( AUC 0-infinity) | VIS410 area under the plasma concentration time curve in serum. AUC 0-infinity is from the time of dosing extrapolated to infinity. | 1, 3, 5, 7, 14, 28, 56, 100 days | 
| VIS410 Plasma Concentration (AUC 0-last) | VIS410 area under the plasma concentration time curve in serum. AUC 0-last is the area under the plasma concentration time curve from time 0 to the last measurable concentration. | 1, 3, 5, 7, 14, 28, 56, 100 days | 
| Half-life of VIS410 in Serum. | Terminal elimination half-life of VIS410 in serum (t1/2) in serum. | 1, 3, 5, 7, 14, 28, 56, 100 days | 
| Clearance (CL) of VIS410 in Serum. | Summary of VIS410 total clearance (CL) in serum. | 1, 3, 5, 7, 14, 28, 56, 100 days | 
| Area Under the Viral Load-Time Curve (VL AUC) From Nasopharyngeal Swab Day 7. | The difference between VIS410 and placebo treatment groups in viral AUC based on the half-maximal tissue culture infective dose (TCID50) from nasopharyngeal swab samples taken from the first 50 participants. | 7 days | 
| Peak Viral Load by TCID50 | The difference between VIS410 and placebo treatment groups in peak viral load based on the half-maximal tissue culture infective dose (TCID50) from nasopharyngeal swab samples taken from the first 50 participants. | 7 days | 
| Time to Resolution of Peak Viral Load From Nasopharyngeal Samples by TCID50. | The number of days for the median time to resolution of peak viral load from end of infusion by nasopharyngeal swabs collected from the first 50 participants and tested by half maximal tissue culture infective dose (TCID50) | 7 days | 
| Summary of Anti-VIS410 Antibody (ADA) Titers. | Count of subjects testing positive for anti-VIS410 antibodies on days 1, 14, 56 and 100. A positive result includes samples confirmed positive and above titer cut point factor (and titer ≥ 1). Negative results include screened or confirmed negative or confirmed positive but below titer cut point factor (titer < 1). For participants receiving placebo, only samples from two participants were tested at Days 14 and 56. | 100 days | 
| Duration of Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410 | The Influenza Patient Reported Outcome (FluPRO) questionnaire is a 32-question instrument that assesses the occurrence and intensity of influenza associated symptoms (scale of 0 to 4, with 0 representing no symptoms) over 24 hours (lower scores indicate better outcomes). FluPRO data were recorded by subjects at Baseline (Day 1), then daily thereafter through Day 10. Data below show the time to symptom resolution for Total Symptom Score. | 10 days |