Clinical trial to see if there are differences in flu symptoms when people receive a single infusion of VIS410, the study medicine, compared with those who receive placebo and to find out if VIS410 is safe and well tolerated

• Register: EUCTR
• Last refreshed on: 11 December 2017
• Main ID: EUCTR2015-004546-26-LV
• Date of registration: 16/12/2016
• Prospective Registration: Yes
• Primary sponsor: Visterra, Inc.
• Public title: Clinical trial to see if there are differences in flu symptoms when people receive a single infusion of VIS410, the study medicine, compared with those who receive placebo and to find out if VIS410 is safe and well tolerated
• Scientific title: A Phase 2a Double-blind, Placebo-controlled Study to Assess the Safety and Tolerability of a Single Intravenous Dose of VIS410 in Subjects with Uncomplicated Influenza A Infection
• Date of first enrolment: 06/01/2017
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004546-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Estonia, Latvia, Lithuania, Serbia, South Africa, Ukraine, United States

Contacts

• Name: Ellie Hershberger, PharmD
• Affiliation: Visterra, Inc.

• Name: Ellie Hershberger, PharmD
• Affiliation: Visterra, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects meeting all of the following criteria are eligible to participate in this study:
1. Male and female subjects aged =18 years and < 65 years
2. Women should fulfill one of the following criteria:
a. Post-menopausal; either amenorrhea =12 months or follicle stimulating hormone >40 mIU/mL as documented in their medical history.
b. Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation.
c. Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from screening until 60 days post-infusion, per Section 7.1.2.
3. 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 Section 7.1.2) when having heterosexual intercourse, from screening until 60 days post-infusion.
4. 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
5. 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
6. Onset of symptoms (time when the oral temperature was first measured as either decreased [oral temperature of < 95°F or < 35°C] or elevated [oral 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
7. Subject is able and willing to comply with study procedures, as per protocol
8. Subject is able and willing to give voluntary written informed consent
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 150
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion Criteria:
Subjects meeting any of the following criteria are excluded from participation in this study:
1. Use of NSAIDs or antihistamines within 6 hours of study drug dosing with the exception of those used as part of the pretreatment regimen.
2. History of intolerance or allergic response to monoclonal antibodies and/or pretreatment medications diphenhydramine, ibuprofen and acetylsalicylic acid)
3. History of receiving monoclonal antibody products within 3 months prior to enrollment in this study or planned administration during the study period
4. Subjects in whom nasopharyngeal swabbing is not possible
5. Subject weight less than (<) 45 kg
6. 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, active tuberculosis, neuromuscular disorders, seizure disorders or cognitive dysfunction.
7. History of chronic GI disease, including bleeding, ulceration, Irritable Bowel Syndrome, systemic mastocytosis or chronic diarrhea
8. Women who are pregnant, breast-feeding, or considering becoming pregnant.
9. Patients with hypoxemia requiring oxygen support.
10. 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
11. Presence of immunocompromised status due to chronic illness, previous organ transplant, or use of immunosuppressive medical therapy including systemic steroids.
12. Presence of known Acquired Immune Deficiency Syndrome-defining illness, chronic hepatitis B or hepatitis C.
13. 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
14. 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
15. Presence of any pre-existing illness that, in the opinion of the Investigator, would place the subject at an unreasonably increased risk through participation in this study
16. Subjects unable to comply with study protocol procedures and study visit schedules for whatever reason
17. Subjects unable to take oral predose medication
18. 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
19. Subjects on chronic medications where the dose has not been stable for at least 3 months


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Influenza A infection
MedDRA version: 19.0 Level: LLT Classification code 10022002 Term: Influenza A virus infection System Organ Class: 100000004862

Intervention(s)

Product Code: VIS410
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: VIS410
Other descriptive name: VIS410
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: •Evaluate the efficacy of 2 dose levels of VIS410 compared with placebo on the time to alleviation of clinical symptoms of acute uncomplicated influenza
•Evaluate the effect of 2 dose levels of VIS410 on severity of influenza infection
•Assess the pharmacokinetics of 2 dose levels of VIS410 in serum
•Assess the effects of 2 dose levels of VIS410 on viral shedding
•Assess the immunogenicity of 2 dose levels of VIS410

Main Objective: Assess the safety and tolerability of a single intravenous (IV) infusion of 2 dose levels of VIS410 in patients with uncomplicated influenza infection

Primary end point(s): Primary Endpoints:
• The proportion of subjects with adverse events (AEs) and serious adverse events (SAEs) following administration of VIS410
• The proportion of subjects with treatment-emergent AEs (TEAEs) including hypersensitivity reaction, anaphylactic reaction, and AEs of special interest (AESIs) following dosing

Timepoint(s) of evaluation of this end point: The primary endpoints will be evaluated throughout the study, as
assesments are done. End points defined by adverse events can be
reached at any time.

Secondary Outcome(s)

Secondary end point(s): Secondary Endpoints:
• The incidence, severity, and 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
• Percentage of participants requiring hospitalization for influenza-related complications
• Duration of hospitalization for influenza-related complications
• Percentage of participants with complications of influenza
• Percentage of participants with influenza A relapse/reinfection
• VIS410 pharmacokinetic (PK) parameters (Cmax, tmax, AUC0-8, AUC0-last, t1/2, Vd, CL) in serum
• The difference between VIS410 and placebo treatment groups in viral AUC from nasopharyngeal swabs
• The difference between VIS410 and placebo treatment groups in peak viral load and time to resolution of viral load from nasopharyngeal swabs
• Titer of anti-VIS410 antibody-positive samples

Timepoint(s) of evaluation of this end point: The secondary endpoints will be evaluated throughout the study, as
assesments are done. End points defined by adverse events can be
reached at any time.

Secondary ID(s)

2015-004546-26-BG

VIS410-202

Source(s) of Monetary Support

Visterra, Inc.