Safety and Reactogenicity of a H1N1 Influenza Challenge Virus in Healthy Volunteers

NCT02014870 | Completed Phase 1 DMC

• 2 other identifiers: H1N1_CS_012013-002503-34
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to determine the dose level of live, wild-type A/California/ H1N1 2009 virus that has an appropriate safety and illness/infectivity profile to be used as an influenza virus, challenge strain in future intervention studies. Illness parameters were collected by subject symptom scores as well as by physical examination. Virus parameters were measured by PCR and cell culture assay (performed by VisMederi srl).

Conditions

Influenza A

Keywords

Influenza; Vaccine; Virus; H1N1; Challenge; Vismederi

Outcome Measures

Primary Outcomes (2)

• Safety

  Frequency and severity of treatment-emergent adverse events as a measure of which dose of H1N1 challenge virus is safe for future intervention studies

  Day 1 - 29

• Infectivity

  Frequency and severity of influenza signs and symptoms experienced and incidence of laboratory confirmed infections, as a measure of which dose of H1N1 virus induces an appropriate level of illness/ infectivity for future intervention studies

  Day 1- 8

Secondary Outcomes (3)

• Kinetics

  Day 1 -8

• Immunology

  Day 1 - 29

• Biomarkers

  Day 1 -29

Study Arms (3)

Cohort 1

EXPERIMENTAL

1:1000 dilution of neat virus

Other: 1:1000 Live wild-type A/California/H1N1 2009

Cohort 2

EXPERIMENTAL

1:100 dilution of neat virus

Other: 1:100 Live wild-type A/California/H1N1 2009

Cohort 3

EXPERIMENTAL

1:10 dilution of neat virus

Other: 1:10 Live wild-type A/California/H1N1 2009

Interventions

1:1000 Live wild-type A/California/H1N1 2009 OTHER

1:1000 dilution of neat virus

Also known as: virus

Cohort 1

1:100 Live wild-type A/California/H1N1 2009 OTHER

1:100 dilution of neat virus

Also known as: Virus

Cohort 2

1:10 Live wild-type A/California/H1N1 2009 OTHER

1:10 dilution of neat virus

Also known as: Virus

Cohort 3

Eligibility Criteria

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

You may qualify if:

• Male or female aged 18-45 years inclusive.
• Able to give written informed consent to participate.
• Healthy, as determined by medical history, physical examination, vital signs, 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 titre of ≤ 10 prior to challenge.
• Non-habitual smoker (habitual smokers are persons who smoke more than 4 cigarettes or other tobacco products on a weekly basis) and agree to not use tobacco products during participation in the study.
• Females should fulfil one of the following criteria:
• At least one year post-menopausal;
• Surgically sterile;
• 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 (e.g., 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.
• Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1.
• 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 for 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.
• Suffering from asthma, bronchiectasis, emphysema, chronic obstructive pulmonary disease or any other chronic lung disease.
• Pregnant or who is breast feeding.
• Diastolic BP \< 50 or \> 90 mmHg, a systolic BP \< 100 or \> 150 mmHg, a pulse \< 50 or \> 100 bpm after resting for 5 min.
• Current use or use within the last 7 days of intranasal corticosteroids.
• 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 3 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.
• 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 age 5 years or younger, within 2 weeks following challenge.
• Anticipated presence of a household contact age 65 years or older, within 2 weeks following challenge.

Sponsors & Collaborators

• Immune Targeting Systems Ltd: lead

Study Sites (1)

SGS Life Sciences

Antwerp, Belgium

Location

Related Publications (2)

• Muller J, Parizotto E, Antrobus R, Francis J, Bunce C, Stranks A, Nichols M, McClain M, Hill AVS, Ramasamy A, Gilbert SC. Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials. J Transl Med. 2017 Jun 8;15(1):134. doi: 10.1186/s12967-017-1235-3.

  PMID: 28595644 DERIVED

• Watson JM, Francis JN, Mesens S, Faiman GA, Makin J, Patriarca P, Treanor JJ, Georges B, Bunce CJ. Characterisation of a wild-type influenza (A/H1N1) virus strain as an experimental challenge agent in humans. Virol J. 2015 Feb 3;12:13. doi: 10.1186/s12985-015-0240-5.

  PMID: 25645025 DERIVED

MeSH Terms

Conditions

Influenza, Human; Virus Diseases

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 18, 2013
• Study Start: June 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 18, 2013

Record last verified: 2013-12

Locations

BE (1)