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

NCT ID: NCT04086472

Last Updated: 2022-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-28
• Study Completion Date: 2020-08-14

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Clesrovimab 100 mg

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

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: BIOLOGICAL

Single dose of clesrovimab administered via IV infusion.

RSV-A Memphis 37b

Intervention Type: BIOLOGICAL

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

Clesrovimab 200 mg

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

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: BIOLOGICAL

Single dose of clesrovimab administered via IV infusion.

RSV-A Memphis 37b

Intervention Type: BIOLOGICAL

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

Clesrovimab 300 mg

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

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: BIOLOGICAL

Single dose of clesrovimab administered via IV infusion.

RSV-A Memphis 37b

Intervention Type: BIOLOGICAL

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

Clesrovimab 900 mg

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

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: BIOLOGICAL

Single dose of clesrovimab administered via IV infusion.

RSV-A Memphis 37b

Intervention Type: BIOLOGICAL

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

RSV-A Memphis 37b

Intervention Type: BIOLOGICAL

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

Interventions

Clesrovimab

Single dose of clesrovimab administered via IV infusion.

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: OTHER

RSV-A Memphis 37b

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

Intervention Type: BIOLOGICAL

Other Intervention Names

MK-1654

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

HVIVO Services Ltd ( Site 0001)

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: RESULT

PMID: 34775220 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-1654-002

Identifier Type: OTHER

Identifier Source: secondary_id

2018-003347-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1654-005

Identifier Type: -

Identifier Source: org_study_id