Clinical trial to compare the benefit and safety of a single infusion of VIS410, the study medicine added to standard Tamiflu® treatment to that of treatment with Tamiflu® alone in hospitalized adults with flu infection requiring oxygen support

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2016-004009-15-ES
• Date of registration: 09/06/2017
• Prospective Registration: Yes
• Primary sponsor: Visterra, Inc.
• Public title: Clinical trial to compare the benefit and safety of a single infusion of VIS410, the study medicine added to standard Tamiflu® treatment to that of treatment with Tamiflu® alone in hospitalized adults with flu infection requiring oxygen support
• Scientific title: Phase 2b, Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of Intravenous VIS410 in Addition to Oseltamivir (Tamiflu®) Compared With Oseltamivir Alone in Hospitalized Adults With Influenza A Infection Requiring Oxygen Support
• Date of first enrolment: 03/07/2017
• Target sample size: 390
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004009-15
• 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: yes; Placebo: no; 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

Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Colombia, Estonia, France, Georgia, Guatemala, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Peru, Portugal, Romania, Russian Federation, Serbia, Singapore, South Africa, Spain, Thailand, Turkey, Ukraine, United Kingdom, 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. For a country where the legal age of consent is >18 years old, the country requirements should be followed.
2. Test positive for influenza A by rapid antigen test or with another commercially available test on an adequate nasopharyngeal specimen in accordance with the manufacturer's instructions, or an acceptable local test including, PCR, FIA, or ELISA
3. Onset of influenza symptoms no more than 5 days before VIS410/placebo infusion; symptoms may include cough, dyspnea, sore throat, fever, myalgias, headache, nasal symptoms (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea, and vomiting.
4. Need for supplemental oxygen of at least 40% (4 L/min) and/or hypoxemia defined as SpO2 of less than 90%
5. Women of childbearing potential must have a negative pregnancy test within 2 days prior to VIS410/placebo infusion.
6. 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 relations must be willing to use adequate contraception from screening until 60 days post VIS410/placebo infusion (see Section 6.2).
7. 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 6.2) when having heterosexual intercourse, from screening until 60 days post VIS410/placebo infusion.
8. Subject is able and willing to comply with study procedures, as per protocol.
9. Subject, or a legally authorized representative (LAR), is able to understand the purpose and risks of the study 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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 190

Exclusion criteria:
Subjects meeting any of the following criteria are excluded from participation in this study:
1. Known or suspected intolerance or hypersensitivity to VIS410, oseltamivir, pretreatment medications (diphenhydramine, or to both ibuprofen and acetylsalicylic acid [ASA]), or closely related compounds (eg, other monoclonal antibodies)
2. History of receiving monoclonal antibody products (including VIS410) within 3 months prior to VIS410/placebo dosing or planned administration during the study period
3. Subjects who have taken more than 6 doses of an approved antiviral therapy for influenza within the prior 96 hours (eg, oral oseltamivir, inhaled zanamivir, IV peramivir, or oral ribavirin) between onset of symptoms and VIS410/placebo dosing
4. Subjects with influenza B infection
5. Subjects with lung transplant or history of severe chronic lung disease or any condition requiring > 2 L/minute of home oxygen therapy (ie, severe chronic obstructive pulmonary disease [COPD], pulmonary fibrosis)
6. Subjects on extracorporeal membrane oxygenation (ECMO) at time of randomization
7. Subjects with active graft-vs-host disease, hematopoietic stem cell transplant within the previous 90 days, or human immunodeficiency virus infection with a CD4 cell count of less than 200 per cubic millimeter
8. Hospitalization for > 48 hours prior to randomization
9. High probability of mortality within 48 hours of randomization as determined by the Investigator
10. Women who are pregnant, breast-feeding, or considering to become pregnant
11. Subjects in whom nasopharyngeal swabbing is not possible
12. Subjects weighing less than 45 kg
13. 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
14. Presence of any preexisting illness that, in the opinion of the Investigator, would place the subject at an unreasonably increased risk through participation in this study
15. Subjects unable to comply with study protocol procedures and study visit schedules for whatever reason
16. 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


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

Health Condition(s) or Problem(s) studied

Influenza A infection in hospitalized patients who need supplemental oxygen
MedDRA version: 20.0 Level: LLT Classification code 10022002 Term: Influenza A virus infection System Organ Class: 100000004862

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

Intervention(s)

Product Code: VIS410
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: VIS410
Current Sponsor code: 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

Trade Name: Aspirin NSAID GeriCare
Pharmaceutical Form: Tablet

Trade Name: Ibuprofen Tablets, USP AMNEAL
Pharmaceutical Form: Tablet

Trade Name: DiphenhydrAMINE HCl Injection, USP
Pharmaceutical Form: Injection

Trade Name: Diphenhydramine Hydrochloride capsules, USP
Pharmaceutical Form: Capsule

Primary Outcome(s)

Secondary Objective: • Evaluate the effect of VIS410 + oseltamivir vs oseltamivir alone on the following endpoints:
? Viral titer in upper respiratory samples
? Time to clinical response
? Time to cessation of ventilator support
? Time to resumption of normal activities
? All-cause and attributable 14- and 28-day mortality
? Healthcare resource utilization
? Time to alleviation of clinical symptoms of influenza in subset of subjects able to complete the FluPRO Questionnaire at baseline and post-dose
? Proportion of subjects with new documented bacterial pneumonia/superinfection
? Proportion of subjects with influenza-related complications
• Pharmacokinetics of VIS410 in serum
• Immunogenicity of VIS410
• Emergence of resistance to VIS410 and oseltamivir

Main Objective: The primary efficacy objective is to evaluate the effect of 2 dose levels of VIS410 + oseltamivir on the time to normalization of respiratory function compared to oseltamivir alone.
The primary safety objective is to evaluate safety and tolerability of 2 dose levels of a single intravenous (IV) dose of VIS410 when administered in combination with oseltamivir in hospitalized subjects with influenza A infection.

Primary end point(s): The primary efficacy endpoint is the time to cessation of O2 support resulting in a stable SpO2 > 95% for at least 6 hours on room air, return to baseline respiratory status, or hospital discharge with no need for additional O2 support, whichever occurs first.
The primary safety endpoint is the proportion of subjects with AEs and SAEs following administration of VIS410.

Timepoint(s) of evaluation of this end point: The endpoints can be evaluated by hospital staff at any time while the patient is hospitalized or during patient visit in case of a discharged patient.

Secondary Outcome(s)

Secondary end point(s): The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in the following endpoints:
• Peak viral load, viral AUC, duration of viral shedding, and time to resolution of viral load from nasopharyngeal swabs by TCID50 and qRT-PCR
• Time to clinical response defined as resolution of at least 4 of 5 vital signs
? Afebrile with temperature = 37.8°C, without use of antipyretics
? Oxygen saturation > 95% on room air without support or return to pre-infection status, if pre-infection status was < 95%
? Pulse rate = 100/min
? Systolic blood pressure (SBP) = 90 mm/Hg, without vasopressor use
? Respiratory rate < 24 beats per minute
• Total number of days on ventilation
• Number of days to resumption of usual activities
• All-cause and attributable mortality rates at Day 14 and 28
• Total number of days in hospital and/or intensive care unit (ICU) from admission to discharge and rate of rehospitalization due to influenza A relapse/complication
• The incidence, severity, and duration of signs and symptoms of influenza-like illness as assessed by the FluPRO Questionnaire (see Appendix 14.1)
• The percentage of subjects with new bacterial pneumonia/superinfection
• The percentage of subjects with influenza-related complications
• VIS410 population pharmacokinetic (PK) parameters in serum
• Titer of anti-VIS410 antibody positive samples
• Genotypic and/or phenotypic assessment to determine the emergence of VIS410 and oseltamivir-resistant viruses

Timepoint(s) of evaluation of this end point: The endpoints can be evaluated by hospital staff at any time while the patient is hospitalized or during patient visit in case of a discharged patient.

Secondary ID(s)

VIS410-203

Source(s) of Monetary Support

Visterra, Inc.