Single Ascending Dose Challenge Study to Determine Safety and Reactogenicity of an Influenza Challenge Virus

NCT04106817 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: WCCTG 14-01
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a non-controlled, open-label, single-center, dose-escalation study to determine the safety, infectivity, and immune responses elicited from of the potential influenza virus challenge strain. The study objective is to determine the dose with the optimal safety profile and infectivity rate of the viral challenge strain in healthy volunteers for use in subsequent challenge intervention studies to test potential influenza vaccines and/or therapeutics.

Conditions

Influenza

Outcome Measures

Primary Outcomes (2)

• Viral Shedding

  Number of participants with viral shedding, assessed from nasopharyngeal swabs using RT-PCR and cell culture assay

  Day 9

• Seroconversion

  Greater than or equal to 4-fold rise in HAI titer by study Day 60 relative to baseline

  Day 60

Secondary Outcomes (1)

• Number and Severity of AEs

  Day 60

Study Arms (3)

Cohort 1

EXPERIMENTAL

1:10 dilution of neat virus (0.25mL of 1:10 dilution per nostril of neat virus; approximate quantity 3.5 x 10\^6TCID50/dose)

Biological: Live, wild-type A/California/H1N1 2009 influenza virus

Cohort 2

EXPERIMENTAL

1:5 dilution of neat virus (0.25mL of 1:5 dilution per nostril of neat virus; approximate quantity 7 x 10\^6TCID50/dose)

Biological: Live, wild-type A/California/H1N1 2009 influenza virus

Cohort 3

EXPERIMENTAL

1:10 dilution of neat virus (0.5mL of 1:10 dilution per nostril of neat virus; approximate quantity 7 x 10\^6TCID50/dose)

Biological: Live, wild-type A/California/H1N1 2009 influenza virus

Interventions

Live, wild-type A/California/H1N1 2009 influenza virus BIOLOGICAL

Live, wild type influenza A virus that was inoculated and manufactured in allantoic fluid of SPF embryonated hen eggs

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, as determined by medical history, physical examination, vital signs, echocardiogram, 12-lead ECG, and clinical safety laboratory examinations at baseline, as determined by the Investigator.
• Absent or low levels of detectable pre-existing antibodies to influenza virus subtypes, including as a minimum the challenge strain, as determined by an HAI titer of ≤10 prior to challenge.
• Non-smoker (no smoking within the last year and a history of less than 10 packs per year total) and agree to not use tobacco products during participation in the study.
• Female subjects of childbearing potential must:
• Not be breastfeeding
• Have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1
• Will use oral, implantable, transdermal, or injectable contraceptives for 30 days prior to administration of the A/California/H1N1 2009 virus until the follow-up visit is performed.
• Use another reliable form of contraception approved by the Investigator (eg, intrauterine device, female condom, diaphragm with spermicide, cervical cap, use of condom by the sexual partner or a sterile sexual partner) from the time of screening until the follow-up visit is performed.
• Female subjects not of childbearing potential must:
• Be at least 1 year post-menopausal, or
• Be surgically sterile
• Male subjects able to father a child and sexually active with a female of childbearing potential, must agree to use a double barrier method of birth control (eg, condom with spermicidal foam, cream gel) and to not donate sperm during the study, from the day of enrollment until the Day 60 (±3) follow-up visit. If the female partner is using an effective method of contraception, a single barrier method of birth control for the male is acceptable.
• Comprehension of the study requirements, expressed availability for the required study period, and ability to be quarantined for up to 10 days and to attend the scheduled follow up visit.
• Negative alcohol and urine drug screening tests prior to entering quarantine.
• Being willing to adhere to the prohibitions and restrictions specified in this protocol

You may not qualify if:

• Prior receipt of any influenza vaccine within the previous 2 years.
• Significant adulthood history of seasonal hay fever or a seasonal allergic rhinitis or perennial allergic rhinitis or chronic or nasal or sinus condition such as chronic sinusitis.
• Abnormal nasal structure including septal deviation and nasal polyps, or surgery to the nose or nasopharynx within 6 months of signing the informed consent form or recent (within the last 6 months) history of frequent or prolonged episodes of epistaxis.
• Suffering from asthma, bronchiectasis, emphysema, chronic obstructive pulmonary disease or any other chronic lung disease. A history of childhood asthma before the age of 12 is acceptable provided the subject is asymptomatic without treatment. Subjects with a single episode of wheezing after age 12 (lasting less than 8 weeks) can be included at the investigator's discretion.
• A female who is pregnant or who is breast feeding
• Diastolic BP, systolic BP or, pulse not consistent with normal vital signs, based on investigator judgment.
• Current use or use of intranasal corticosteroids within the last 30 days prior to the administration of the investigational virus product (Study Day 1).
• Presence of significant uncontrolled medical, neurological or psychiatric illness (acute or chronic) as assessed by the Investigator. This includes, but is not limited to, institution of new surgical or medical treatment for a chronic condition), or a significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening and reconfirmed on Day -1 prior to challenge.
• Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies.
• Cancer or treatment for cancer, within 5 years, excluding basal cell carcinoma of the skin, which is allowed.
• Presence of immunosuppression or any medical condition that may be associated with impaired immune responsiveness, including, but not limited to, diabetes mellitus inflammatory bowel disease.
• Presently receiving (or history of receiving) or during the preceding 3-month period prior to screening, any medications or other treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable) azathioprine or mercaptopurine. Topical corticosteroids except intranasal will be allowed. Use of intranasal corticosteroids within the last 30 days prior to the administration of the investigational virus product (Study Day 1) is prohibited.
• Chronic condition requiring prescription or over-the-counter medicine, with the exception of vitamins.
• Anticipated presence of a household contact with documented severe immunosuppression (as defined by CD4 \< 200/mm³ or an absolute neutrophil count \< 1500/mm³), either as a result of disease and/or therapy.
• Anticipated presence of a household contact aged ≤ 5 years, aged \> 64 years, or a pregnant contact within 2 weeks following challenge.

Sponsors & Collaborators

• WCCT Global: lead
• Stanford University: collaborator
• National Institutes of Health (NIH): collaborator

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Associate Director of Regulatory Affairs
• Organization: WCCT Global

erin.flynn@wcct.com

7207713080

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2019
• First Posted: September 27, 2019
• Study Start: January 19, 2015
• Primary Completion: August 10, 2015
• Study Completion: August 10, 2015
• Last Updated: January 14, 2020
• Results First Posted: November 19, 2019

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share