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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04086472
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 5
• Actual Duration (Months): 9.6
• Patients Per Site Per Month: 8.4

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine if a single intravenous (IV) dose of MK-1654 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 MK-1654 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.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Viruses	Biological: MK-1654; Other: Placebo; Biological: RSV-A Memphis 37b	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: Oct 28, 2019
• Actual Primary Completion Date: Mar 22, 2020
• Actual Study Completion Date: Aug 14, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Area Under the Viral Load-time Curve (VL-AUC) [10 days; from Day 2 through Day 11 (inclusive) after viral inoculation (Study Day 31 through Day 40)]

   The VL-AUC will be determined by reverse transcription qualitative integrated cycler polymerase chain reaction (RT-qPCR) after viral inoculation.

Secondary Outcome Measures

1. Percentage of Participants With Symptomatic Respiratory Syncytial Virus (RSV) Infection [10 days; from Day 2 through Day 11 (inclusive) after viral inoculation (Study Day 31 through Day 40)]

   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.

2. Number of Participants With an Adverse Event (AE) [Up to 187 days]

   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.

3. Number of Participants With a Serious Adverse Event (SAE) [Up to 187 days]

   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.

4. Serum Concentration of MK-1654 [Predose and Days 1 (1, 2, and 4 hours postdose), 8, 15, 29, 40, and 57]

   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.

5. Concentration of RSV Serum Neutralizing Antibody Titers [Days 1, 29, 40, and 57]

   RSV serum neutralization titers were determined by enzyme-linked immunosorbent assay (ELISA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HVIVO Services Ltd ( Site 0001)	London		United Kingdom	E1 2AX

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 13, 2020

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT04086472
• Other Study ID Numbers: 1654-005; MK-1654-002; 2018-003347-28
• First Posted: Sep 11, 2019
• Last Update Posted: May 5, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Virus Diseases

Study Results

Participant Flow

Recruitment Details	Healthy adult male and female participants were recruited at a single study site in the United Kingdom.

Arm/Group Title	MK-1654 100 mg	MK-1654 200 mg	MK-1654 300 mg	MK-1654 900 mg	Placebo
Arm/Group Description	Participants receive a single intravenous (IV) infusion of MK-1654 100 mg on Day 1.	Participants receive a single IV infusion of MK-1654 200 mg on Day 1.	Participants receive a single IV infusion of MK-1654 300 mg on Day 1.	Participants receive a single IV infusion of MK-1654 900 mg on Day 1.	Participants receive a single IV infusion of placebo on Day 1.
Period Title: Overall Study
STARTED	16	16	16	16	16
Received MK-1654 or Placebo	16	16	16	16	16
Inoculated With Respiratory Syncytial Virus (RSV) A Memphis 37b	14	14	14	13	15
Not Inoculated	2	2	2	3	1
COMPLETED	12	14	14	13	14
NOT COMPLETED	4	2	2	3	2

Baseline Characteristics

Arm/Group Title	MK-1654 100 mg	MK-1654 200 mg	MK-1654 300 mg	MK-1654 900 mg	Placebo	Total
Arm/Group Description	Participants receive a single IV infusion of MK-1654 100 mg on Day 1.	Participants receive a single IV infusion of MK-1654 200 mg on Day 1.	Participants receive a single IV infusion of MK-1654 300 mg on Day 1.	Participants receive a single IV infusion of MK-1654 900 mg on Day 1.	Participants receive a single IV infusion of placebo on Day 1.	Total of all reporting groups
Overall Participants	16	16	16	16	16	80
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	30.4 (6.9)	27.1 (8.3)	27.6 (8.7)	26.4 (4.5)	25.3 (4.1)	27.4 (6.8)
Sex: Female, Male (Count of Participants)
Female	4 25%	5 31.3%	12 75%	5 31.3%	9 56.3%	35 43.8%
Male	12 75%	11 68.8%	4 25%	11 68.8%	7 43.8%	45 56.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.3%	0 0%	0 0%	0 0%	0 0%	1 1.3%
Not Hispanic or Latino	15 93.8%	16 100%	16 100%	16 100%	16 100%	79 98.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 6.3%	2 12.5%	0 0%	1 6.3%	1 6.3%	5 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 6.3%	0 0%	0 0%	0 0%	1 1.3%
White	14 87.5%	11 68.8%	14 87.5%	15 93.8%	14 87.5%	68 85%
More than one race	1 6.3%	2 12.5%	2 12.5%	0 0%	1 6.3%	6 7.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized participants who received a dose of study drug, a RSV inoculation, and had data available are included.

Arm/Group Title	MK-1654 100 mg	MK-1654 200 mg	MK-1654 300 mg	MK-1654 900 mg	Placebo
Arm/Group Description	Participants receive a single IV infusion of MK-1654 100 mg on Day 1.	Participants receive a single IV infusion of MK-1654 200 mg on Day 1.	Participants receive a single IV infusion of MK-1654 300 mg on Day 1.	Participants receive a single IV infusion of MK-1654 900 mg on Day 1.	Participants receive a single IV infusion of placebo on Day 1.
Measure Participants	13	13	14	13	15
Least Squares Mean (95% Confidence Interval) [log10 copies-/ml*days]	19.94	14.74	16.44	15.33	21.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-1654 100 mg, Placebo
	Comments	Treatment vs. Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.808
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares (LS) Mean Difference
	Estimated Value	-1.31
	Confidence Interval	(2-Sided) 90%; -10.25 to 7.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-1654 200 mg, Placebo
	Comments	Treatment vs. Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.229
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.51
	Confidence Interval	(2-Sided) 90%; -15.46 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-1654 300 mg
	Comments	Treatment vs. Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.363
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.81
	Confidence Interval	(2-Sided) 90%; -13.58 to 3.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MK-1654 900 mg, Placebo
	Comments	Treatment vs. Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.273
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.92
	Confidence Interval	(2-Sided) 90%; -14.87 to 3.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Symptomatic Respiratory Syncytial Virus (RSV) Infection
Description	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.
Time Frame	10 days; from Day 2 through Day 11 (inclusive) after viral inoculation (Study Day 31 through Day 40)

Outcome Measure Data

Analysis Population Description

All randomized participants who received a dose of study drug, a RSV inoculation, and had data available are included.

Arm/Group Title	MK-1654 100 mg	MK-1654 200 mg	MK-1654 300 mg	MK-1654 900 mg	Placebo
Arm/Group Description	Participants receive a single IV infusion of MK-1654 100 mg on Day 1.	Participants receive a single IV infusion of MK-1654 200 mg on Day 1.	Participants receive a single IV infusion of MK-1654 300 mg on Day 1.	Participants receive a single IV infusion of MK-1654 900 mg on Day 1.	Participants receive a single IV infusion of placebo on Day 1.
Measure Participants	13	13	14	13	15
Number (95% Confidence Interval) [Percentage of Participants]	53.85 336.6%	30.77 192.3%	35.71 223.2%	30.77 192.3%	53.33 333.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-1654 100 mg, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Treatment vs. Placebo
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; -36.57 to 37.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI based on the Chan and Zhang exact method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-1654 200 mg, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Treatment vs. Placebo
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-22.56
	Confidence Interval	(2-Sided) 95%; -56.70 to 15.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI based on the Chan and Zhang exact method

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-1654 300 mg, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Treatment vs. Placebo
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-17.62
	Confidence Interval	(2-Sided) 95%; -53.09 to 20.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI based on the Chan and Zhang exact method

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MK-1654 900 mg, Placebo
	Comments	Treatment vs. Placebo
	Type of Statistical Test	Other
	Comments	Treatment vs. Placebo
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-22.56
	Confidence Interval	(2-Sided) 95%; -56.70 to 15.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI based on the Chan and Zhang exact method

3. Secondary Outcome

Title	Number of Participants With an Adverse Event (AE)
Description	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.
Time Frame	Up to 187 days

Outcome Measure Data

Analysis Population Description

All participants who received any study intervention are included.

Arm/Group Title	MK-1654 100 mg	MK-1654 200 mg	MK-1654 300 mg	MK-1654 900 mg	Placebo
Arm/Group Description	Participants receive a single IV infusion of MK-1654 100 mg on Day 1.	Participants receive a single IV infusion of MK-1654 200 mg on Day 1.	Participants receive a single IV infusion of MK-1654 300 mg on Day 1.	Participants receive a single IV infusion of MK-1654 900 mg on Day 1.	Participants receive a single IV infusion of placebo on Day 1.
Measure Participants	16	16	16	16	16
Number [Participants]	11 68.8%	12 75%	12 75%	8 50%	11 68.8%

4. Secondary Outcome

Title	Number of Participants With a Serious Adverse Event (SAE)
Description	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.
Time Frame	Up to 187 days

Outcome Measure Data

Analysis Population Description

All participants who received any study intervention are included.

Arm/Group Title	MK-1654 100 mg	MK-1654 200 mg	MK-1654 300 mg	MK-1654 900 mg	Placebo
Arm/Group Description	Participants receive a single IV infusion of MK-1654 100 mg on Day 1.	Participants receive a single IV infusion of MK-1654 200 mg on Day 1.	Participants receive a single IV infusion of MK-1654 300 mg on Day 1.	Participants receive a single IV infusion of MK-1654 900 mg on Day 1.	Participants receive a single IV infusion of placebo on Day 1.
Measure Participants	16	16	16	16	16
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Serum Concentration of MK-1654
Description	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.
Time Frame	Predose and Days 1 (1, 2, and 4 hours postdose), 8, 15, 29, 40, and 57

Outcome Measure Data

Analysis Population Description

All randomized participants who received MK-1654 and had no major protocol deviations are included.

Arm/Group Title	MK-1654 100 mg	MK-1654 200 mg	MK-1654 300 mg	MK-1654 900 mg
Arm/Group Description	Participants receive a single IV infusion of MK-1654 100 mg on Day 1.	Participants receive a single IV infusion of MK-1654 200 mg on Day 1.	Participants receive a single IV infusion of MK-1654 300 mg on Day 1.	Participants receive a single IV infusion of MK-1654 900 mg on Day 1.
Measure Participants	16	16	16	16
Predose	0.0369 (0.148)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 1, 1 hour postdose	16.4 (3.13)	36.0 (6.65)	62.6 (16.8)	134 (45.1)
Day 1, 2 hours postdose	34.3 (6.42)	72.6 (12.5)	125 (25.7)	298 (46.8)
Day 1, 4 hours postdose	33.3 (6.19)	68.8 (11.5)	122 (26.9)	287 (46.0)
Day 8	16.0 (2.54)	33.0 (5.48)	56.7 (12.8)	140 (24.1)
Day 15	14.5 (2.49)	29.1 (4.19)	47.6 (8.57)	123 (21.6)
Day 29	11.9 (2.11)	23.1 (3.06)	38.5 (6.99)	103 (16.0)
Day 40	10.2 (1.74)	21.4 (3.18)	35.6 (7.16)	88.5 (13.4)
Day 57	9.46 (2.01)	18.7 (2.60)	32.3 (6.14)	79.5 (15.5)

6. Secondary Outcome

Title	Concentration of RSV Serum Neutralizing Antibody Titers
Description	RSV serum neutralization titers were determined by enzyme-linked immunosorbent assay (ELISA).
Time Frame	Days 1, 29, 40, and 57

Outcome Measure Data

Analysis Population Description

All randomized participants who received a dose of study drug, a RSV inoculation, and had data available for the time point are included.

Arm/Group Title	MK-1654 100 mg	MK-1654 200 mg	MK-1654 300 mg	MK-1654 900 mg	Placebo
Arm/Group Description	Participants receive a single IV infusion of MK-1654 100 mg on Day 1.	Participants receive a single IV infusion of MK-1654 200 mg on Day 1.	Participants receive a single IV infusion of MK-1654 300 mg on Day 1.	Participants receive a single IV infusion of MK-1654 900 mg on Day 1.	Participants receive a single IV infusion of placebo on Day 1.
Measure Participants	16	16	16	16	16
Day 1, Predose	669.1	699.3	954.0	893.8	837.4
Day 1, 2 hours postdose	11137.6	24836.1	41544.8	100163.5	1225.4
Day 29	4727.2	8135.8	13263.2	31367.8	1037.1
Day 40	4517.1	8357.6	13510.9	27935.5	1540.4
Day 57	4377.8	5531.9	11557.9	22209.6	1500.2

Adverse Events

Time Frame	Up to 187 days
Adverse Event Reporting Description	All participants who received a dose of any study intervention are included.
Arm/Group Title	MK-1654 100 mg		MK-1654 200 mg		MK-1654 300 mg		MK-1654 900 mg		Placebo
Arm/Group Description	Participants receive a single IV infusion of MK-1654 100 mg on Day 1.		Participants receive a single IV infusion of MK-1654 200 mg on Day 1.		Participants receive a single IV infusion of MK-1654 300 mg on Day 1.		Participants receive a single IV infusion of MK-1654 900 mg on Day 1.		Participants receive a single IV infusion of placebo on Day 1.
All Cause Mortality
	MK-1654 100 mg		MK-1654 200 mg		MK-1654 300 mg		MK-1654 900 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Serious Adverse Events
	MK-1654 100 mg		MK-1654 200 mg		MK-1654 300 mg		MK-1654 900 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	MK-1654 100 mg		MK-1654 200 mg		MK-1654 300 mg		MK-1654 900 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/16 (68.8%)		12/16 (75%)		12/16 (75%)		8/16 (50%)		11/16 (68.8%)
Gastrointestinal disorders
Abdominal discomfort	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Abdominal pain upper	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0
Constipation	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Diarrhoea	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Haemorrhoids	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Nausea	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Odynophagia	2/16 (12.5%)	2	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Vomiting	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0
General disorders
Catheter site bruise	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Immune system disorders
Seasonal allergy	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Infections and infestations
Bronchitis viral	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0
COVID-19	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Gastroenteritis	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0
Nasopharyngitis	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0
Oral candidiasis	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Oral herpes	1/16 (6.3%)	1	0/16 (0%)	0	1/16 (6.3%)	1	2/16 (12.5%)	2	0/16 (0%)	0
Upper respiratory tract infection	1/16 (6.3%)	1	3/16 (18.8%)	4	3/16 (18.8%)	3	1/16 (6.3%)	1	2/16 (12.5%)	2
Viral pharyngitis	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0
Injury, poisoning and procedural complications
Contusion	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Nasal injury	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Investigations
Alanine aminotransferase increased	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	1/16 (6.3%)	1
Aspartate aminotransferase increased	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Body temperature increased	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0
C-reactive protein increased	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0
SARS-CoV-2 test positive	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	2	0/16 (0%)	0	0/16 (0%)	0
Back pain	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0
Musculoskeletal pain	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Neck pain	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Nervous system disorders
Headache	6/16 (37.5%)	8	6/16 (37.5%)	6	5/16 (31.3%)	6	5/16 (31.3%)	7	3/16 (18.8%)	3
Presyncope	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0
Psychiatric disorders
Depression	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0
Renal and urinary disorders
Dysuria	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0
Reproductive system and breast disorders
Dysmenorrhoea	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	1/16 (6.3%)	1
Epistaxis	1/16 (6.3%)	1	1/16 (6.3%)	7	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Nasal congestion	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0
Oropharyngeal pain	1/16 (6.3%)	1	1/16 (6.3%)	1	3/16 (18.8%)	4	0/16 (0%)	0	0/16 (0%)	0
Rhinorrhoea	2/16 (12.5%)	2	1/16 (6.3%)	1	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Dry skin	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Psoriasis	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	1/16 (6.3%)	1
Rash	0/16 (0%)	0	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Vascular disorders
Phlebitis	1/16 (6.3%)	1	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0	0/16 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.