Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04086472
Recruitment Status : Recruiting
First Posted : September 11, 2019
Last Update Posted : November 21, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : October 28, 2019
Estimated Primary Completion Date : April 14, 2020
Estimated Study Completion Date : April 14, 2020

Arm Intervention/treatment
Experimental: MK-1654 Dose 1
Participants receive a single IV infusion of MK-1654 Dose 1 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 Dose 2
Participants receive a single IV infusion of MK-1654 Dose 2 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 Dose 3
Participants receive a single IV infusion of MK-1654 Dose 3 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 Dose 4
Participants receive a single IV infusion of MK-1654 Dose 4 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.




Primary Outcome Measures :
  1. Area Under the Viral Load-time Curve (VL-AUC) [ Time Frame: 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. Incidence of Symptomatic RSV Infection [ Time Frame: 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) [ Time Frame: Up to 180 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) [ Time Frame: Up to 180 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 [ Time Frame: Days 1, 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 [ Time Frame: Days 1, 29, 40, and 57 ]
    RSV serum neutralization titers will be determined by measuring the ability of RSV to enter target cells in vitro when incubated in the presence of serial dilutions of the participant's serum.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 chilbrearing 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 immunesuppression), 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 oC 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04086472


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Layout table for location information
United Kingdom
HVIVO Services Ltd ( Site 0001) Recruiting
London, United Kingdom, E1 2AX
Contact: Study Coordinator    +442077561300      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04086472    
Other Study ID Numbers: 1654-005
2018-003347-28 ( EudraCT Number )
MK-1654-002 ( Other Identifier: Merck Protocol Number )
First Posted: September 11, 2019    Key Record Dates
Last Update Posted: November 21, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Layout table for additional information
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:
Layout table for MeSH terms
Virus Diseases