Phase 2a Respiratory Syncytial Virus (RSV) Human Challenge Study of Clesrovimab (MK-1654) in Healthy Participants (MK-1654-005)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2a Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-1654 in Healthy Participants Inoculated With Experimental Respiratory Syncytial Virus

Conditions
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Respiratory Syncytial Viruses

Intervention / Treatment
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* Biological: Clesrovimab
* Other: Placebo
* Biological: RSV-A Memphis 37b


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clesrovimab 100 mg<br>Participants receive a single IV infusion of clesrovimab 100 mg on Day 1. | Biological: Clesrovimab<br>* Single dose of clesrovimab administered via IV infusion.<br>* Other names: MK-1654;Biological: RSV-A Memphis 37b<br>* Approximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation.<br>|
| Experimental: Clesrovimab 200 mg<br>Participants receive a single IV infusion of clesrovimab 200 mg on Day 1. | Biological: Clesrovimab<br>* Single dose of clesrovimab administered via IV infusion.<br>* Other names: MK-1654;Biological: RSV-A Memphis 37b<br>* Approximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation.<br>|
| Experimental: Clesrovimab 300 mg<br>Participants receive a single IV infusion of clesrovimab 300 mg on Day 1. | Biological: Clesrovimab<br>* Single dose of clesrovimab administered via IV infusion.<br>* Other names: MK-1654;Biological: RSV-A Memphis 37b<br>* Approximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation.<br>|
| Experimental: Clesrovimab 900 mg<br>Participants receive a single IV infusion of clesrovimab 900 mg on Day 1. | Biological: Clesrovimab<br>* Single dose of clesrovimab administered via IV infusion.<br>* Other names: MK-1654;Biological: RSV-A Memphis 37b<br>* Approximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation.<br>|
| Placebo Comparator: Placebo<br>Participants receive a single IV infusion of placebo on Day 1. | Other: Placebo<br>* Placebo (0.9% sodium chloride, USP sterile saline) administered via IV infusion.<br>Biological: RSV-A Memphis 37b<br>* Approximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Viral Load-time Curve (VL-AUC) | The VL-AUC will be determined by reverse transcription qualitative integrated cycler polymerase chain reaction (RT-qPCR) after viral inoculation. | 10 days; from Day 2 through Day 11 (inclusive) after viral inoculation (Study Day 31 through Day 40) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Symptomatic Respiratory Syncytial Virus (RSV) Infection | Symptomatic RSV infection is defined as presence of at least 2 quantifiable RT-qPCR at ≥2 consecutive days, plus symptoms of either any grade from 2 different symptoms from the Subject Symptom Card (SSC) or at least one Grade 2 symptom from ≥1 respiratory categories. | 10 days; from Day 2 through Day 11 (inclusive) after viral inoculation (Study Day 31 through Day 40) | 
| Number of Participants With an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Up to 187 days | 
| Number of Participants With a Serious Adverse Event (SAE) | An SAE is any untoward medical occurrence in a clinical study participant that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. | Up to 187 days | 
| Serum Concentration of MK-1654 | The post-dosing concentration of MK-1654 will be determined in serum. On Day 1, 3 samples will be taken at 1, 2, and 4 hours after administration. | Predose and Days 1 (1, 2, and 4 hours postdose), 8, 15, 29, 40, and 57 | 
| Concentration of RSV Serum Neutralizing Antibody Titers | RSV serum neutralization titers were determined by enzyme-linked immunosorbent assay (ELISA). | Days 1, 29, 40, and 57 |