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RV16UB

Phase 1

Asthma | Monoclonal antibody | Respiratory |Merck & Company, Inc.|Last Updated: Sep 4, 2018

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDBiomarker
Total Trials1
Total Enrollment59
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01866306A Study to Evaluate the Safety and Use of Human Rhinovirus in Healthy and Asthmatic Participants (MK-0000-218)PHASE1 COMPLETED 59Oct 22, 2013Jan 18, 2016Sep 4, 2018 -
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Study Endpoints
Primary Endpoints
Number of Healthy and Asthmatic Participants With Events of Clinical Interest (ECI) (Part 1)
Up to Day 24

ECI are selected non-serious and serious adverse events which include the following: an overdose of Sponsor's product; requirement for systemic steroids to treat asthma exacerbation related to virus challenge; acute reaction to virus challenge, confirmed through repeat measurement and when considered potentially associated with administration of virus; specified vital sign findings within 4hr of challenge; specified symptom findings within 24hr of challenge; \>20% decrease in Forced Expiratory Volume in 1 second (FEV1) relative to baseline within 4hr of challenge; dyspnea associated with drop in FEV1 (within 4hr of challenge) that is unresponsive to a bronchodilator rescue agent within 20 minutes; Grade 2+ deviation from normal values of liver-related laboratory parameters at any time between challenge and day 14.

Number of Participants With Serious Adverse Events (SAE) (Parts 1 and 2)
Up to Day 24

A SAE is any adverse event occurring at any dose or during any use of the Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing in-patient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event.

Number of Asthmatic Participants Treated With a Viral Dose of 100 TCID50 With Challenge Induced Upper Airway Symptoms (Part 1)
Day 1 up to Day 7

Asthmatic participants from Part 1 were treated with RV16UB virus at a dose of 100 TCID50, and challenge induced upper airway symptoms were monitored with a diary recording Jackson Cold Symptom Score (CSS). The CSS measures 8 cold symptoms, with each symptom scored from 0 (absent) to 3 (severe). The total score ranges from 0-24, with higher scores reflecting greater severity. The number of participants with a CSS score equal or greater than 3 for two days in a row are presented.

Time -Weighted Average (TWA) Percent Change From Baseline (CFB) in Morning FEV1 in Asthmatic Participants on Days 1-7 (Part 2)
Baseline and Days 1 - 7

Log-transformed FEV1 data were fit by Bayesian hierarchical longitudinal models, with a random participant effect and a fixed categorical effect for day. All baseline (day -7 to day -1) FEV1 were assumed to be with equal mean. FEV1 assessments obtained between 3 am to 3 pm were counted as morning measurements. The TWA CFB morning FEV1 on days 1-7 was calculated as the difference of the mean of estimated day 1-7 morning FEV1 value and the corresponding estimated baseline value. The 95% Confidence Interval actually refers to a 95% Credible Interval. The anticipated mean reduction from baseline is 10%.

TWA Percent CFB in Evening FEV1 in Asthmatic Participants on Days 1-7 (Part 2)
Baseline and Days 1- 7

Log-transformed FEV1 data were fit by Bayesian hierarchical longitudinal models, with a random participant effect and a fixed categorical effect for day. All baseline (day -7 to day -1) FEV1 were assumed to be with equal mean. FEV1 assessments obtained between 3 pm to next day 3 am were counted as evening measurements. The TWA CFB evening FEV1 on days 1-7 was calculated as the difference of the mean of estimated day 1-7 evening FEV1 value and the corresponding estimated baseline value. The FEV1 readings on the evenings of sputum inductions were excluded from the analyses. The 95% Confidence Interval actually refers to a 95% Credible Interval. The anticipated mean reduction from baseline is 10%.

Change From Baseline in Mean Maximum Jackson Cold Symptom Score (CSS) on Days 1 to 14 in Asthmatic Participants (Part 1)
Baseline and Days 1 - 14

Asthmatic participants from Part 1 were treated with RV16UB virus, and challenge induced upper airway symptoms were monitored with a diary recording CSS. The CSS measures 8 cold symptoms, with each symptom scored from 0 (absent) to 3 (severe). The total score ranges from 0-24, with higher scores reflecting greater severity, and a positive change from baseline indicating worsening symptoms.

Number of Asthmatic Participants Demonstrating at Least 10^3 Copies/ml of Viral RNA in Nasal Lavage Fluid on Days 1 to 14 (Part 1)
Days 1 - 14

Viral RNA was measured by real time reverse transcriptase polymerase chain reaction (qRT-PCR) from nasal lavage fluid collected on day 3 and day 7 from asthmatic participants, and the number of participants with at least 10\^3 copies/ml was determined.

Secondary Endpoints
Mean Percent Change From Baseline in Maximum Drop FEV1 of Asthmatic Participants (Part 2)
Baseline and up to day 7
Mean Change From Baseline in TWA Asthma Control Diary (ACD) Score of Asthmatic Participants on Days 3 to 10 (Part 2)
Baseline and Days 3 to 10
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeDIAGNOSTIC
Treatment Arms
ArmTypeDescription
Healthy 10 TCID50 (Part 1)EXPERIMENTALHealthy participants were treated with 10 Tissue Culture Infective Dose 50 (TCID50) administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Healthy 100 TCID50 (Part 1)EXPERIMENTALHealthy participants were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Healthy 1000 TCID50 (Part 1)EXPERIMENTALHealthy participants were treated with 1000 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Asthmatic non-LABA 10 TCID50 (Part 1)EXPERIMENTALParticipants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 10 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Asthmatic non-LABA 100 TCID50 (Part 1)EXPERIMENTALParticipants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Asthmatic LABA 100 TCID50 (Part 1)EXPERIMENTALParticipants with mild to moderate asthma, concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Asthmatic non-LABA 100 TCID50 (Part 2)EXPERIMENTALParticipants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Interventions
NameTypeDescription
RV16UBBIOLOGICALRV16UB is administered by spraying an atomized viral suspension into a single nostril. Planned doses of RV16UB in Part 1 are 10 Tissue Culture Infective Dose 50 (TCID50), 100 TCID50, 1000 TCID50 and 10,000 TCID50.
LABADRUGAsthmatic participants were treated with LABA as part of their standard of care
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Eligibility Criteria
Age Range18 Years — 55 Years
SexALL
Healthy VolunteersYes

Inclusion Criteria: Parts 1 and 2: * have a Body Mass Index (BMI) between =\< 35 kg/m\^2 and \> 17 kg/m\^2 * female of childbearing potential is not pregnant and agrees to use 2 acceptable methods of birth control until 10 days after the last visit,; or female is of non-childbearing potential * is...

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