Efficacy and Safety of CR6261 in an H1N1 Influenza Healthy Volunteer Human Challenge Model
Condition: H1N1 Influenza Healthy Volunteers
MeSH terms: Influenza, Human
Intervention: CR6261; Placebo
Intervention description: 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).
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Influenza A; H1N1; Challenge Model; Human Immunoglobulin and H1N1; Efficacy and Safety in H1N1

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.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Greater than or equal to 18 and less than or equal to 45 years of age.

          2. Non-smoker.

          3. Willingness to remain in isolation for the duration of viral shedding (at a minimum 10
             days) and to comply with all study requirements.

          4. A male subject is eligible for the study if he agrees to practicing abstinence or
             using a condom with spermicide plus an acceptable form of contraception (see inclusion
             criteria 5) being used by any female partner from 4 weeks before to 12 weeks after
             intranasal challenge with influenza.

          5. A female participant is eligible for this study if she is not pregnant or breast
             feeding and 1 of the following:

               -  Of nonchildbearing potential (i.e., women who have had a hysterectomy or tubal
                  ligation or are postmenopausal, as defined by no menses in greater than or equal
                  to 1 year).

               -  Of childbearing potential but agrees to practice effective contraception or
                  abstinence for 4 weeks prior to and 8 weeks after administration of the influenza
                  challenge virus. Acceptable methods of contraception include a male partner who
                  is sterile and is the sole sexual partner of the female participant or a male
                  partner who uses a condom with spermicide plus 1 or more of the following: 1)
                  implants of levonorgestrel; 2) injectable progestogen; 3) an intrauterine device
                  with a documented failure rate of <1%; 4) oral contraceptives; and 5) double
                  barrier method including diaphragm.

          6. Willing to have samples stored for future research.

          7. Prechallenge serum HAI titer against the challenge virus less than or equal to 1:10
             within 60 days of admission for the study.

          8. HIV uninfected confirmed by testing within 60 days of admission for the study.

          9. Agrees to abstain from alcohol intake 24 hours before admission on Day -1, during the
             inpatient period of the study, and 24 hours prior to all other outpatient clinic
             visits.

         10. Agrees to not use over-the-counter medications (including aspirin, decongestants,
             antihistamines, and other NSAIDs), and herbal medication (including, but not limited
             to, herbal tea, St. John s Wort), within 14 days prior to study drug administration
             through the final follow-up visit, unless approved by the investigator.

        EXCLUSION CRITERIA:

          1. Presence of self-reported or medically documented significant medical condition
             including but not limited to:

               1. Chronic pulmonary disease (e.g., asthma, emphysema).

               2. Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure,
                  cardiac surgery, ischemic heart disease, known anatomic defects).

               3. Chronic medical conditions requiring close medical follow-up or hospitalization
                  during the past 5 years (e.g., insulin dependent diabetes mellitus, renal
                  dysfunction, hemoglobinopathies).

               4. Immunosuppression or ongoing malignancy.

               5. Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy,
                  stroke, seizures).

               6. Postinfectious or postvaccine neurological sequelae.

               7. Hyperlipidemia requiring medical therapy per current American College of
                  Cardiology (ACC) and American Heart Association (AHA) guidelines published in
                  2013.

          2. Have close or household (i.e., share the same apartment or house) high-risk contacts
             including but not limited to:

               1. Persons greater than or equal to 65 years of age.

               2. Children less than or equal to 5 years of age.

               3. Residents of nursing homes.

               4. Persons of any age with significant chronic medical conditions such as:

                    -  Chronic pulmonary disease (e.g., severe asthma, COPD).

                    -  Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart
                       failure, cardiac surgery, ischemic heart disease, known anatomic defects).

                    -  Contacts who required medical follow-up or hospitalization during the past 5
                       years because of chronic metabolic disease (e.g., insulin dependent diabetes
                       mellitus, renal dysfunction, hemoglobinopathies).

                    -  Immunosuppression or cancer.

                    -  Neurological and neurodevelopmental conditions (e.g., cerebral palsy,
                       epilepsy, stroke, seizures).

                    -  Individuals who are receiving long-term aspirin therapy.

                    -  Women who are pregnant or who are trying to become pregnant.

          3. Positive serology for hepatitis C virus antibody or hepatitis B surface antigen.

          4. Individual with body mass index (BMI) greater than or equal to 18 and greater than or
             equal to 35 or weight > 114kg.

          5. Acute illness within 7 days of admission and inoculation with the challenge virus (Day
             -1).

          6. Complete blood count (CBC) with differential outside of the NIH Department of
             Laboratory Medicine (DLM) normal reference range and deemed clinically significant by
             the PI.

          7. Chemistries in the acute care, mineral, and/or hepatic panels, and/or any of the
             following: lactate dehydrogenase, uric acid, creatine kinase, and total protein
             outside of the NIH DLM normal reference range and deemed clinically significant by the
             PI.

          8. Amylase or Lipase outside of the NIH DLM normal reference range and deemed clinically
             significant by the PI.

          9. Urinalysis outside of the NIH DLM normal reference range and deemed clinically
             significant by the PI.

         10. Clinically significant abnormality as deemed by the PI on electrocardiogram.

         11. Clinically significant abnormality as deemed by the PI on echocardiographic (ECHO)
             testing.

         12. Clinically significant abnormality as deemed by the PI on the Pulmonary Function Test
             (PFT).

         13. Known allergy to treatments for influenza (including but not limited to oseltamivir,
             nonsteroidals).

         14. Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins,
             fluoroquinolones, or glycopeptides).

         15. Receipt of blood or blood products (including immunoglobulins) within 3 months prior
             to enrollment.

         16. Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is
             greater) prior to enrollment.

         17. Receipt of any non-influenza-related unlicensed vaccine within 6 months prior to
             enrollment.

         18. Self-reported or known history of current alcoholism or drug abuse, or positive
             urine/serum test for drugs of abuse and/or ethanol (i.e., amphetamines, cocaine,
             benzodiazepines, opiates, or metabolites, but not tetrahydrocannabinol (THC) or
             metabolites).

         19. Self-reported or known history of psychiatric or psychological issues deemed by the PI
             to be a contraindication to protocol participation.

        19. Known close contact with anyone known to have influenza in the past 7 days.

        21. Known or suspected hypersensitivity to CR6261 or its excipients (sucrose, L-histidine,
        L-histidine monohydrochloride, polysorbate 20).

        22. History of a previous severe allergic reaction with generalized urticaria, angioedema,
        or anaphylaxis.

        23. Drinks more than 1200 mL (or 5 cups of 240 mL per cup) of tea/coffee/cocoa/cola or
        other caffeinated beverage per day more than 1 day per week in the 2 weeks before
        screening.

        24. Any condition or event that, in the judgment of the PI, is a contraindication to
        protocol participation or impairs the volunteer s ability to give informed consent.