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

NCT04086472 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 1654-005MK-1654-0022018-003347-28
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Respiratory Syncytial Viruses

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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)

• Number of Participants With an Adverse Event (AE)

  Up to 187 days

• Number of Participants With a Serious Adverse Event (SAE)

  Up to 187 days

• Serum Concentration of MK-1654

  Predose and Days 1 (1, 2, and 4 hours postdose), 8, 15, 29, 40, and 57

• Concentration of RSV Serum Neutralizing Antibody Titers

  Days 1, 29, 40, and 57

Study Arms (5)

Clesrovimab 100 mg

EXPERIMENTAL

Participants receive a single IV infusion of clesrovimab 100 mg on Day 1.

Biological: Clesrovimab; Biological: RSV-A Memphis 37b

Clesrovimab 200 mg

EXPERIMENTAL

Participants receive a single IV infusion of clesrovimab 200 mg on Day 1.

Biological: Clesrovimab; Biological: RSV-A Memphis 37b

Clesrovimab 300 mg

EXPERIMENTAL

Participants receive a single IV infusion of clesrovimab 300 mg on Day 1.

Biological: Clesrovimab; Biological: RSV-A Memphis 37b

Clesrovimab 900 mg

EXPERIMENTAL

Participants receive a single IV infusion of clesrovimab 900 mg on Day 1.

Biological: Clesrovimab; Biological: RSV-A Memphis 37b

Placebo

PLACEBO COMPARATOR

Participants receive a single IV infusion of placebo on Day 1.

Other: Placebo; Biological: RSV-A Memphis 37b

Interventions

Clesrovimab BIOLOGICAL

Single dose of clesrovimab administered via IV infusion.

Also known as: MK-1654

Clesrovimab 100 mg; Clesrovimab 200 mg; Clesrovimab 300 mg; Clesrovimab 900 mg

Placebo OTHER

Placebo (0.9% sodium chloride, USP sterile saline) administered via IV infusion.

Placebo

RSV-A Memphis 37b BIOLOGICAL

Approximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation.

Clesrovimab 100 mg; Clesrovimab 200 mg; Clesrovimab 300 mg; Clesrovimab 900 mg; Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

HVIVO Services Ltd ( Site 0001)

London, E1 2AX, United Kingdom

Location

Related Publications (1)

• Maas BM, Lommerse J, Plock N, Railkar RA, Cheung SYA, Caro L, Chen J, Liu W, Zhang Y, Huang Q, Gao W, Qin L, Meng J, Witjes H, Schindler E, Guiastrennec B, Bellanti F, Spellman DS, Roadcap B, Kalinova M, Fok-Seang J, Catchpole AP, Espeseth AS, Stoch SA, Lai E, Vora KA, Aliprantis AO, Sachs JR. Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis. EBioMedicine. 2021 Nov;73:103651. doi: 10.1016/j.ebiom.2021.103651. Epub 2021 Nov 11.

  PMID: 34775220 RESULT

MeSH Terms

Interventions

MK-1654

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: September 11, 2019
• Study Start: October 28, 2019
• Primary Completion: March 22, 2020
• Study Completion: August 14, 2020
• Last Updated: September 14, 2022
• Results First Posted: April 13, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)