Phase 2a Respiratory Syncytial Virus (RSV) Human Challenge Study of Clesrovimab (MK-1654) in Healthy Participants (MK-1654-005)
Condition: Respiratory Syncytial Viruses
MeSH terms: Virus Diseases
Intervention: Clesrovimab; Placebo; RSV-A Memphis 37b
Intervention description: Single dose of clesrovimab administered via IV infusion.; Placebo (0.9% sodium chloride, USP sterile saline) administered via IV infusion.; Approximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of this study is to determine if a single intravenous (IV) dose of
      clesrovimab when administered at 1 of 4 dose levels results in a reduction in viral load
      after intranasal inoculation (with RSV A Memphis 37b) compared to IV placebo. It is
      hypothesized that at least 1 of the 4 dose levels of clesrovimab given prior to inoculation
      will reduce the area under the viral load-time curve (VL-AUC) from Day 2 through Day 11
      (inclusive) after viral inoculation (Study Day 31 through Day 40) compared to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is a male or female 18 to 55 years of age in good health with no history of major
             medical conditions that will interfere with participant safety, as defined by medical
             history, physical examination (including vital signs), electrocardiogram (ECG), and
             routine laboratory tests and determined by the Investigator at a screening evaluation.

          -  Has a total body weight ≥ 50 kg and Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 30kg/m^2.

          -  If male, agrees to study contraceptive requirements at dosing and continuing until 90
             days after dosing or 28 days after viral inoculation (whichever is later) and to not
             donate sperm until 90 days after dosing.

          -  If female, has a negative pregnancy test at screening and prior to dosing and agrees
             to use one form of highly effective contraception if a woman of childbearing potential
             (WOCBP), or is not a WOCBP.

          -  Has serology results within 90 days of dosing that suggest the participant is
             sensitive to RSV infection (i.e., that they are likely to become infected following
             inoculation).

        Exclusion Criteria:

          -  Is a female who is breastfeeding or has been pregnant within 6 months prior to
             enrollment.

          -  Has a history or evidence of any clinically significant or currently active
             cardiovascular, respiratory, dermatological, gastrointestinal, endocrinological,
             haematological, hepatic, immunological (including immune suppression), metabolic,
             urological, renal, neurological, or psychiatric disease (including participants with a
             history of depression and/or anxiety with associated severe psychiatric comorbidities.

          -  Has 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 inoculation (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).

          -  Has any clinically significant history of epistaxis (large nosebleeds) within the last
             3 months prior to IMP dosing and/or history of being hospitalized due to epistaxis on
             any previous occasion.

          -  Has a history or currently active symptoms suggestive of upper or lower respiratory
             tract infection within 6 weeks prior to dosing.

          -  Has any other major disease that, in the opinion of the Investigator, may interfere
             with a participant completing the study and necessary investigations.

          -  Has a history of anaphylaxis-and/or a history of severe allergic reaction or
             significant intolerance to any food or drug, as assessed by the investigator.

          -  Has confirmed positive test for drugs of abuse prior to randomization.

          -  Has a 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).

          -  Is positive for human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV),
             or C (HCV) test.

          -  Has evidence of receipt of vaccine within the 4 weeks prior to IMP dosing.

          -  Has intention to receive any vaccine(s) before the last day of Follow-up.

          -  Receipt of blood or blood products, or loss (including blood donations) of 470 mL or
             more of blood during the 3 months prior IMP dosing or planned during the 3 months
             after the final visit.

          -  Has use within 7 days prior to IMP dosing of any medication or product (prescription
             or over-the-counter), for symptoms of hay fever, dermatitis, nasal congestion or
             respiratory tract infections including the use of regular nasal or dermal
             corticosteroids or antibiotics, apart from those allowed in the study.

          -  Has received systemic (intravenous and/or oral) glucocorticoids or systemic antiviral
             drugs within 6 months prior to IMP dosing.

          -  Has received chronic (defined as more than 14 continuous days) or current
             administration of a systemic immunosuppressant or other immune modifying drug,
             including any dose of oral corticosteroids, within 6 months prior to dose
             administration. The use of topical, inhaled, and nasal glucocorticoids will be
             permitted.

          -  Has used or anticipated use during the conduct of the study of concomitant medications
             (prescription and/or non-prescription), including vitamins or herbal and dietary
             supplements within the specified windows (within 7 days prior to IMP dosing), unless
             in the opinion of the Principal Investigator, the medication will not interfere with
             the study procedures, outcomes, or compromise participant safety.

          -  Has a history (participant recall) of receiving any human immunoglobulin preparation

          -  Has received any investigational drug within 3 months prior to IMP dosing.

          -  Has received ≥3 investigational drugs within the previous 12 months prior to IMP
             dosing.

          -  Has prior participation in another Human Viral Challenge study with a respiratory
             virus of the same virus family in the preceding 3 months taken from the date of viral
             challenge in the previous study to the date of expected viral inoculation in this
             study.

          -  Has prior participation in any RSV related (vaccine, monoclonal antibody or small
             molecule) interventional trial.

          -  Has a forced expiratory volume in 1 second (FEV1) < 80%.

          -  Has presence of fever, defined as participant presenting with a temperature reading of
             ≥ 37.9°C on day of IMP dosing.

          -  Has smoked ≥ 10 pack years at any time [10 pack years is equivalent to one pack of 20
             cigarettes a day for 10 years]).

          -  Has venous access deemed inadequate for the phlebotomy and demands of the study.

          -  Presents any concern by the investigator regarding safe participation in the study or
             for any other reason the investigator considers the participant inappropriate for
             participation in the study.

          -  Has any contraindication for IV infusion.

          -  Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or
             child) who is investigational site or Sponsor staff directly involved with this study.