Clinical trial NCT02989194: Study of an Investigational Monoclonal Antibody, VIS410, in Subjects With Uncomplicated Influenza A
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Lead sponsor: Visterra, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2016-12-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: Inclusion Criteria:

* Male and female subjects aged ≥18 years and ˂65 years
* Women should fulfill one of the following criteria:

  1. Post-menopausal; either amenorrhea ≥12 months or follicle stimulating hormone \>40 mIU/mL (milli-international units/milliliter) as documented in their medical history
  2. Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation
  3. 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

Primary outcomes:
measure: Assess the Safety and Tolerability of a Single IV Dose of VIS410 in Participants With Uncomplicated Influenza Infection
timeFrame: 100 days
measure: Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest
timeFrame: 100 days
Secondary outcomes:
measure: 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
timeFrame: 10 days
measure: Hospitalization for Influenza-related Complications
timeFrame: 100 days
measure: Duration of Hospitalization for Complications of Influenza
timeFrame: 100 days
measure: Count of Participants With Complications of Influenza
timeFrame: 100 days
measure: Influenza A Relapse/Reinfection
timeFrame: 100 days
measure: VIS410 Maximum Plasma Concentration
timeFrame: 1, 3, 5, 7, 14, 28, 56, 100 days
measure: Pharmacokinetics of VIS410 Concentration in Serum
timeFrame: 1, 3, 5, 7, 14, 28, 56, 100 days
measure: VIS410 Plasma Concentration ( AUC 0-infinity)
timeFrame: 1, 3, 5, 7, 14, 28, 56, 100 days
measure: VIS410 Plasma Concentration (AUC 0-last)
timeFrame: 1, 3, 5, 7, 14, 28, 56, 100 days
measure: Half-life of VIS410 in Serum.
timeFrame: 1, 3, 5, 7, 14, 28, 56, 100 days
measure: Clearance (CL) of VIS410 in Serum.
timeFrame: 1, 3, 5, 7, 14, 28, 56, 100 days
measure: Area Under the Viral Load-Time Curve (VL AUC) From Nasopharyngeal Swab Day 7.
timeFrame: 7 days
measure: Peak Viral Load by TCID50
timeFrame: 7 days
measure: Time to Resolution of Peak Viral Load From Nasopharyngeal Samples by TCID50.
timeFrame: 7 days
measure: Summary of Anti-VIS410 Antibody (ADA) Titers.
timeFrame: 100 days
measure: 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
timeFrame: 10 days
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Coral Gables
country: United States
state: Florida
city: Homestead
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Eunice
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Shelby
country: United States
state: North Carolina
city: Houston
country: United States
state: Texas
city: McAllen
country: United States
state: Texas
city: Asenovgrad
country: Bulgaria
city: Lom
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Velingrad
country: Bulgaria
city: Paide
country: Estonia
city: Tallinn
country: Estonia
city: Tallinn
country: Estonia
city: Tallinn
country: Estonia
city: Daugavpils
country: Latvia
city: Liepaja
country: Latvia
city: Rezekne
country: Latvia
city: Riga
country: Latvia
city: Valmiera
country: Latvia
city: Ventspils
country: Latvia
city: Kragujevac
country: Serbia
city: Nis
country: Serbia
city: Novi Sad
country: Serbia
city: Welkom
country: South Africa
state: Free State
city: Benoni
country: South Africa
state: Gauteng
city: Centurion
country: South Africa
state: Gauteng
city: Johannesburg
country: South Africa
state: Gauteng
city: Kempton Park
country: South Africa
state: Gauteng
city: Pretoria West
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Soshanguve
country: South Africa
state: Gauteng
city: Soweto
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: Kwazulu Natal
city: Thabazimbi
country: South Africa
state: Limpopo
city: Middelburg
country: South Africa
state: Mpumalanga
city: Witbank
country: South Africa
state: Mpumalanga
city: Cape Town
country: South Africa
state: Western Cape
city: Worcester
country: South Africa
state: Western Cape
city: Kharkiv
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Kiev
country: Ukraine
city: Kiev
country: Ukraine
city: Odesa
country: Ukraine
city: Sumy
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Vinnytsya
country: Ukraine
Study officials:
affiliation: Visterra, Inc.
name: Clinical Development
role: STUDY_DIRECTOR
References:
citation: Hershberger E, Sloan S, Narayan K, Hay CA, Smith P, Engler F, Jeeninga R, Smits S, Trevejo J, Shriver Z, Oldach D. Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study. EBioMedicine. 2019 Feb;40:574-582. doi: 10.1016/j.ebiom.2018.12.051. Epub 2019 Jan 9.