Respiratory Syncytial VirusesPhase 2NCT04086472
Phase 2a Respiratory Syncytial Virus (RSV) Human Challenge Study of Clesrovimab (MK-1654) in Healthy Participants (MK-1654-005)
A Phase 2 study testing Clesrovimab and RSV-A Memphis 37b in people with Respiratory Syncytial Viruses, run by Merck Sharp & Dohme LLC at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Respiratory Syncytial Viruses
- What is being tested?
- Clesrovimab and RSV-A Memphis 37b
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Oct 2019to 14 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- Clesrovimab, Placebo, RSV-A Memphis 37b
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClesrovimabBiological
Also called MK-1654
Single dose of clesrovimab administered via IV infusion.
PlaceboOther
Placebo (0.9% sodium chloride, USP sterile saline) administered via IV infusion.
RSV-A Memphis 37bBiological
Approximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation.
| Study group | Role | What they receive |
|---|---|---|
| Clesrovimab 100 mg | Experimental | Participants receive a single IV infusion of clesrovimab 100 mg on Day 1. Receives: Biological: Clesrovimab; Biological: RSV-A Memphis 37b |
| Clesrovimab 200 mg | Experimental | Participants receive a single IV infusion of clesrovimab 200 mg on Day 1. Receives: Biological: Clesrovimab; Biological: RSV-A Memphis 37b |
| Clesrovimab 300 mg | Experimental | Participants receive a single IV infusion of clesrovimab 300 mg on Day 1. Receives: Biological: Clesrovimab; Biological: RSV-A Memphis 37b |
| Clesrovimab 900 mg | Experimental | Participants receive a single IV infusion of clesrovimab 900 mg on Day 1. Receives: Biological: Clesrovimab; Biological: RSV-A Memphis 37b |
| Placebo | Placebo comparator | Participants receive a single IV infusion of placebo on Day 1. Receives: Other: Placebo; Biological: RSV-A Memphis 37b |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Days 1, 29, 40, and 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2019
- Study start28 Oct 2019
- Primary completion22 Mar 2020
- Study completion14 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Respiratory Syncytial VirusesStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04086472
- Sponsor's protocol ID
- 1654-005
- Other IDs
- MK-1654-002, 2018-003347-28, 2018
- Status last verified
- Aug 2022
- First submitted
- 10 Sep 2019
- Last updated
- 14 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 34775220
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04086472
- Acronym / sponsor ID
- 1654-005
- Conditions
- Respiratory Syncytial Viruses
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 28 Oct 2019 (actual)
- Primary completion
- 22 Mar 2020 (actual)
- Study completion
- 14 Aug 2020 (actual)
- First posted
- 11 Sep 2019 (actual)
- Results
- Posted 13 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Clesrovimab 100 mg | Experimental | Biological: Clesrovimab, Biological: RSV-A Memphis 37bParticipants receive a single IV infusion of clesrovimab 100 mg on Day 1. |
| Clesrovimab 200 mg | Experimental | Biological: Clesrovimab, Biological: RSV-A Memphis 37bParticipants receive a single IV infusion of clesrovimab 200 mg on Day 1. |
| Clesrovimab 300 mg | Experimental | Biological: Clesrovimab, Biological: RSV-A Memphis 37bParticipants receive a single IV infusion of clesrovimab 300 mg on Day 1. |
| Clesrovimab 900 mg | Experimental | Biological: Clesrovimab, Biological: RSV-A Memphis 37bParticipants receive a single IV infusion of clesrovimab 900 mg on Day 1. |
| Placebo | Placebo comparator | Other: Placebo, Biological: RSV-A Memphis 37bParticipants receive a single IV infusion of placebo on Day 1. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClesrovimabAlso: MK-1654Single dose of clesrovimab administered via IV infusion. | Biological | Clesrovimab 100 mg, Clesrovimab 200 mg, Clesrovimab 300 mg, Clesrovimab 900 mg |
| PlaceboPlacebo (0.9% sodium chloride, USP sterile saline) administered via IV infusion. | Other | Placebo |
| RSV-A Memphis 37bApproximately 4Log10 plaque-forming units (PFU)/mL RSV-A virus inoculation strain Memphis 37b administered via intranasal inoculation. | Biological | Clesrovimab 100 mg, Clesrovimab 200 mg, Clesrovimab 300 mg, Clesrovimab 900 mg, Placebo |
Primary outcome
Area Under the Viral Load-time Curve (VL-AUC)
Time frame: 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.
5 secondary outcomes
Percentage of Participants With Symptomatic Respiratory Syncytial Virus (RSV) Infection
Time frame: 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)
Time frame: Up to 187 days
Number of Participants With a Serious Adverse Event (SAE)
Time frame: Up to 187 days
Serum Concentration of MK-1654
Time frame: Predose and Days 1 (1, 2, and 4 hours postdose), 8, 15, 29, 40, and 57
Concentration of RSV Serum Neutralizing Antibody Titers
Time frame: Days 1, 29, 40, and 57
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34775220Maas 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.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clesrovimab and RSV-A Memphis 37b in people with Respiratory Syncytial Viruses, run by Merck Sharp & Dohme LLC at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Viral Load-time Curve (VL-AUC) (time frame: 10 days; from Day 2 through Day 11 (inclusive) after viral inoculation (Study Day 31 through Day 40)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04086472, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2022.