Efficacy and Safety of CR6261 in an H1N1 Influenza Healthy Volunteer Human Challenge Model
Condition: H1N1 Influenza Healthy Volunteers
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      - Researchers want to see if a new drug reduces flu disease in people treated with this drug
      versus a placebo. The drug has an antibody that may help the immune system fight the flu.
      Placebo is only sugar and water. All participants will get the flu virus. They may or may not
      develop flu symptoms.

      Objective:

      - To see if the drug CR6261 reduces flu disease in people treated with this drug versus a
      placebo.

      Eligibility:

      - Healthy nonsmokers ages 18 45.

      Design:

        -  Participants will be screened under a separate protocol.

        -  Participants must use contraception or abstinence for several weeks before and after the
           study. They must have no alcohol for 1 day before each visit. Any medicine must be
           approved by the study doctor until after follow-up.

        -  Participants will stay in a hospital isolation unit for at least 10 days.

        -  They will have:

        -  Medical history

        -  Physical exam

        -  Blood and urine tests

        -  Heart and lung test

        -  Tests for drugs and alcohol

        -  Throughout their stay, participants will:

        -  Be closely watched by a medical team

        -  Have nasal washes and swabs several times a day

        -  Participants will have the flu virus sprayed in each nostril.

        -  The next day, participants will get either study drug or placebo through a soft plastic
           tube placed in a vein by needle. It will take 2 hours. They will not know which they
           get.

        -  Participants can go home after 10 days if they test negative for the flu 2 days in a
           row.

        -  Participants will have daily questionnaires at home and 2 follow-up visits over 2
           months.
    

Detailed description: 
      The high morbidity and mortality associated with both pandemic and seasonal influenza and the
      threat of new potentially pandemic strains emerging makes influenza an important infectious
      disease and public health problem. Mean annual estimates of influenza deaths due to seasonal
      influenza alone attributes up to 49,000 deaths in the US and 250,000 to 500,000 deaths in
      industrialized countries to influenza. Pandemics can have an even more devastating effect.
      Public health agencies must continue to be prepared by making attempts to reduce the public
      health impact of this important virus.

      In the realm of influenza therapeutics, antiviral drugs are currently used to treat influenza
      infection in those who fail to be protected by current vaccines or those who do not receive a
      vaccine. Currently, only two classes of antivirals are FDA approved for the treatment of
      influenza A: neuraminidase inhibitors and matrix M2 channel blockers. Although these drugs
      have been shown to be effective in reducing influenza illness by 24-48 hours and reducing
      shedding in relatively healthy adults, as with vaccination, they have had limited
      effectiveness in high risk groups and those who have severe or complicated influenza
      infections. In addition, antiviral resistance has become very common in human influenza A
      viruses, as currently circulating H1N1 and H3N2 strains are resistant to the adamantane M2
      channel blockers and many cases of neuraminidase inhibitor resistance have also been reported
      with strains of both subtypes. This resistance can develop quickly and in most cases only
      requires a single amino acid change. Given these significant issues with currently available
      treatments, novel therapies for influenza are clearly needed.

      Live virus challenge studies have played a pivotal role in developing influenza therapeutics
      in the past, and they will be instrumental in the future. No novel therapeutic or
      prophylactic agent has been FDA-approved since the last influenza challenge studies ceased
      over a decade ago. In collaboration with the Crucell Vaccine Institute (part of Crucell which
      is in the Janssen family of Pharmaceutical Companies of Johnson & Johnson) this protocol will
      evaluate mAb CR6261 for possible therapeutic value. Unlike the current antivirals that are
      compounds which interfere with some portion of the viral replicative cycle, this agent is a
      mAb that targets the stem of HA, neutralizing the virus by stabilizing the pre-fusion state
      and preventing the pH-dependent fusion of viral and cellular membranes. Pre-clinical data
      suggest that this mAb has good cross-protective efficacy with a variety of HA subtypes unlike
      current vaccines, making it potentially effective in the event of an emerging influenza virus
      outbreak with a novel HA subtype. In addition, the conserved nature of the HA stem region
      suggests that amino acid changes conferring resistance are much less likely. We will effort
      to demonstrate that CR6261 leads to improved outcomes compared with placebo with respect to
      the AUC of virus shedding as determined by qPCR in NP swabs in all treated subjects.
    

Intervention name(s): CR6261; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): 50 mg/kg administered as a single 2-hour intravenous infusion on Day 1 (24 hours after virus administration).; Administered as a single 2-hour intravenous infusion on Day 1 (24 hours after virus administration).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: Influenza A; H1N1; Challenge Model; Human Immunoglobulin and H1N1; Efficacy and Safety in H1N1