Exploratory Study to Estimate the Prophylactic Efficacy of Palivizumab in Healthy Adult Participants Inoculated With RSV
Condition: Healthy Adult Participants
Intervention: Palivizumab; Placebo; RSV-A Memphis 37b virus
Intervention description: Liquid solution in sterile water for injection (final concentration of 20mg/mL), intravenous infusion, single dose of 8mg/kg or 15mg/kg, administered at a rate of 1mL/min; Sodium Chloride 0.9% Solution (Normal Saline), intravenous infusion, single dose of 0mg/Kg, administered at a rate of 1mL/min; Single Intranasal Virus Dose (challenge dose is approximately 4.5log10 PFU)
Intervention MeSH terms: Palivizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Double-Blind, Randomised, Placebo-Controlled Exploratory Study to Estimate the Prophylactic
      Efficacy of Palivizumab in Healthy Adult Participants Inoculated with Respiratory Syncytial
      Virus (RSV).
    

Eligibility criteria:

        Inclusion Criteria:

          1. An informed consent document signed and dated by the participant and the Investigator.

          2. Aged between 18 and 55 years old on the day of signing the consent form.

          3. In good health with no history, or current evidence, of clinically significant medical
             conditions, and no clinically significant test abnormalities that will interfere with
             participant safety, as defined by medical history, physical examination, (including
             vital signs), Electrocardiogram (ECG), and routine laboratory tests as determined by
             the Investigator.

          4. A documented medical history prior to enrolment.

          5. The following criteria are applicable to female participants participating in the
             study.

               1. Females of childbearing potential must have a negative pregnancy test prior to
                  enrolment.

               2. Females of non-childbearing potential:

               1. Post- menopausal females; defined as having a history of amenorrhea for >12
                  months with no alternative medical cause, and /or by Follicle stimulating hormone
                  (FSH) level >40mIU/mL, confirmed by laboratory

               2. Documented status as being surgically sterile (e.g. tubal ligation, hysterectomy,
                  bilateral salpingectomy and bilateral oophorectomy).

          6. The following criteria apply to female and male participants:

               1. Female participants of childbearing potential must use one form of highly
                  effective contraception. Hormonal methods must be in place from at least 2 weeks
                  prior to the first study visit. The contraception use must continue until 30 days
                  after the date of viral challenge/last dosing with IMP (whichever occurs last).
                  Highly effective contraception is as described below:

               1. Established use of hormonal methods of contraception described below (for a
                  minimum of 2 weeks prior to the first study visit). When hormonal methods of
                  contraception are used, male partners are required to use a condom with a
                  spermicide:

        1. Oral 2. Intravaginal 3. Transdermal b. Intrauterine device (IUD) c. Intrauterine
        hormone-releasing system (IUS) d. Bilateral tubal ligation e. Male sterilisation (with the
        appropriate post vasectomy documentation of the absence of sperm in the ejaculate) where
        the vasectomised male is the sole partner for that woman.

        f. True abstinence - sexual abstinence is considered a highly effective method only if
        defined as refraining from heterosexual intercourse during the entire period of risk
        associated with the study treatments. The reliability of sexual abstinence needs to be
        evaluated in relation to the duration of the clinical trial and the preferred and usual
        lifestyle of the participant.

        b) Male participants must agree to the contraceptive requirements below at entry to
        quarantine and continuing until 90 days after the date of Viral challenge / last dosing
        with the investigational medicinal product (IMP) (whichever occurs last):

          1. Use a condom with a spermicide to prevent pregnancy in a female partner or to prevent
             exposure of any partner (male and female) to the IMP.

          2. Male sterilisation with the appropriate post vasectomy documentation of the absence of
             sperm in the ejaculate (please note that the use of condom with spermicide will still
             be required to prevent partner exposure). This applies only to males participating in
             the study

          3. In addition, for female partners of childbearing potential, that partner must use
             another form of contraception such as one of the highly effective methods mentioned
             above for female participants.

          4. True abstinence - sexual abstinence is considered a highly effective method only if
             defined as refraining from heterosexual intercourse during the entire period of risk
             associated with the study treatments. The reliability of sexual abstinence needs to be
             evaluated in relation to the duration of the clinical trial and the preferred and
             usual lifestyle of the participant.

        c) In addition to the contraceptive requirements above, male participants must agree not to
        donate sperm following discharge from quarantine until 90 days after the date of Viral
        Challenge/last dosing with IMP (whichever occurs last).

        7. For Part 2 of the study: Sero-suitable to the challenge virus, as defined in the study
        Analytical Plan.

        Exclusion Criteria:

        Medical History

          1. History of, or currently active, symptoms or signs suggestive of upper or lower
             respiratory tract infection within 4 weeks prior to the first study visit.

          2. a) Any history or evidence of any other clinically significant or currently active
             systemic comorbidities including psychiatric disorders (includes participants with a
             history of depression and/or anxiety).

             b) And/or other major disease that, in the opinion of the Investigator, may put the
             participant at undue risk, or interfere with a participant completing the study and
             necessary investigations.

             The following conditions apply:

             • Participants with clinically mild atopic eczema/atopic dermatitis and clinically
             mild psoriasis may be included at the Investigator's discretion (e.g., if small
             amounts of regular topical steroids are used, no eczema in cubital fossa; moderate to
             large amounts of daily dermal corticosteroids is an exclusion).

               -  Rhinitis (including hay fever) which is clinically active or history of moderate
                  to severe rhinitis, or history of seasonal allergic rhinitis likely to be active
                  at the time of inclusion into the study and/or requiring regular nasal
                  corticosteroids on an at least weekly basis, within 30 days of admission to
                  quarantine will be excluded. Participants with a history of currently inactive
                  rhinitis (within the last 30 days) or mild rhinitis may be included at the PI's
                  discretion.

               -  Participants with a physician diagnosed underactive thyroid who have been
                  controlled on treatment for at least 6 months with evidence of a normal thyroid
                  function test (TFT) can be included at the discretion of the PI.

               -  Any concurrent serious illness including history of malignancy that may interfere
                  with the aims of the study or a participant completing the study. Basal cell
                  carcinoma within 5 years of initial diagnosis or with evidence of recurrence is
                  also an exclusion.

                  o Participants with a history of psychiatric illness including depression and/or
                  anxiety of any severity within the last 2 years can be included if the Patient
                  Health Questionnaire (PHQ-9) and / or the Generalised Anxiety Disorder
                  Questionnaire (GAD-7) is less than or equal to 4. Participants with a PHQ-9 or
                  GAD-7 score of between 5 and 9 may be included following consultation with a
                  Senior Physician (Clinical Lead for Screening) who may advise further
                  consultation with the PI.

                  o Participants reporting physician diagnosed migraine can be included provided
                  there are no associated neurological symptoms such as hemiplegia or visual loss.
                  Cluster headache/migraine or prophylactic treatment for migraine is an exclusion.

                    -  Participants with physician diagnosed mild Irritable Bowel Syndrome (IBS)
                       not requiring regular treatment can be included at the discretion of the PI.

          3. Participants who have smoked ≥ 10 pack years at any time [10 pack years is equivalent
             to one pack of 20 cigarettes a day for 10 years]).

          4. A total body weight ≤ 50 kg and Body Mass Index (BMI) ≤18 kg/m2 and ≥30kg/m2

          5. Females who:

               1. Are breastfeeding, or

               2. Have been pregnant within 6 months prior to the study.

          6. History of anaphylaxis-and/or a history of severe allergic reaction or significant
             intolerance to any food or drug, as assessed by the PI.

          7. Venous access deemed inadequate for the phlebotomy and cannulation demands of the
             study.

          8. a) For Part 2 of the study: Any significant abnormality altering the anatomy of the
             nose in a substantial way or nasopharynx that may interfere with the aims of the study
             and in particular any of the nasal assessments or viral challenge, (historical nasal
             polyps can be included, but large nasal polyps causing current and significant
             symptoms and/or requiring regular treatments in the last month will be excluded).

             b) Any clinically significant history of epistaxis (large nosebleeds) within the last
             3 months of the first study visit and/or history of being hospitalized due to
             epistaxis on any previous occasion.

             c) Any nasal or sinus surgery within 3 months of the first study visit. Prior or
             Concomitant Medications and Assessments

          9. For Part 2 of the study:

               1. Evidence of vaccinations within the 4 weeks prior to the planned date of viral
                  challenge/first dosing with IMP (whichever occurs first).

               2. Intention to receive any vaccination(s) before the last day of Follow-up. (NB. No
                  travel restrictions will apply after the Day 28 (±3 days) Follow-up Visit).

         10. Receipt of blood or blood products, or loss (including blood donations) of 470 mL or
             more of blood during the 3 months prior to the planned date of viral challenge/first
             dosing with IMP (whichever occurs first) or planned during the 3 months after the
             final visit.

         11. a) Receipt of any investigational drug within 3 months prior to the planned date of
             viral challenge/first dosing with IMP (whichever occurs first).

             b) Receipt of three or more investigational drugs within the previous 12 months prior
             to the planned date of viral challenge/first dosing with IMP (whichever occurs first).

             For Part 2 of the study:

             c) Prior inoculation with a virus from the same virus-family as the challenge virus.

             d) Prior participation in another human viral challenge study with a respiratory virus
             in the preceding 3 months, taken from the date of viral challenge in the previous
             study to the date of expected viral challenge in this study

         12. a) Confirmed positive test for drugs of abuse on first study visit. One repeat test
             allowed at PI discretion.

             b) History or presence of alcohol addiction, or excessive use of alcohol (weekly
             intake in excess of 28 units alcohol; 1 unit being a half glass of beer, a small glass
             of wine or a measure of spirits), or excessive consumption of xanthine containing
             substances (e.g. daily intake in excess of 5 cups of caffeinated drinks e.g. coffee,
             tea, cola).

         13. For Part 2 of the study:

             A forced expiratory volume in 1 second (FEV1) < 80%.

         14. Positive human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV), or C
             (HCV) test.

             Other

         15. Those employed or immediate relatives of those employed at hVIVO or the Sponsor.

         16. Any other finding that, in the opinion of the Investigator, deems the participant
             unsuitable for the study.