Clinical trial NCT01704040: A Study of CNTO 3157 in Healthy Normal and Asthmatic Participants Inoculated With Human Rhinovirus Type 16
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled Study Evaluating CNTO 3157 in Healthy Normal and Asthmatic Subjects Inoculated With Human Rhinovirus Type 16
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers and Asthma
Keywords: Healthy volunteers and asthma
CNTO 3157
Rhinovirus
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-10-11
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purposes of this study are to evaluate the safety (Parts 1 and 2) and efficacy (Part 2) of pretreatment with CNTO 3157 in healthy adult and asthmatic adult participants before and after intranasal (into the nose) inoculation with human rhinovirus type 16 (HRV-16).

Detailed description: This is a two-part, randomized (participants are assigned to treatment by chance), double-blind (participants and investigators do not know what study agent is being administered), placebo-controlled study. A placebo appears identical to a study agent, has no active ingredients, and helps investigators evaluate the effect of a study agent. In Part 1, following administration of CNTO 3157 or placebo, the severity of an upper respiratory tract infection, due to inoculation with HRV 16, will be assessed in healthy participants for safety reasons. In Part 2, following administration of CNTO 3157 or placebo and inoculation with HRV-16, efficacy and safety will be assessed in asthmatic participants using standard assessments to evaluate asthma treatments. The study (Parts 1 and 2) will be completed when the last participant completes the last visit (Week 11) in Part 2.

Eligibility criteria: Inclusion Criteria:

* Understanding of the study and a signed informed consent form before any study-related procedures
* Willing and able to adhere to the restrictions specified in the protocol
* Results of the following laboratory tests within the following limits: serum alanine aminotransferase (ALT) levels ≤2 x ULN; serum aspartate aminotransferase (AST) levels ≤2 x ULN
* Part 1 (healthy participants):
* a). Body weight in the range of 40 to 125 kg, inclusive. Have a body mass index (BMI) of 19 to 32 kg/m2, inclusive
* b). Healthy with no clinically significant abnormalities as determined by medical history, physical examination, blood chemistry assessments, hematologic assessments, coagulation and urinalysis, measurement of vital signs, and 12-lead electrocardiogram (ECG) performed at Screening Visit 2
* Part 2:
* a). (BMI) of 19 to 40 kg/m2, inclusive; have a physician-documented diagnosis of asthma for at least 6 months prior to Screening Visit 2; have stable asthma based on physician assessment at Screening Visit 2
* b). Have an Asthma Control Questionnaire (ACQ) symptom score less than (\<)2.5 at Screening Visit 2
* c). Have a prebronchodilator forced expiratory volume in the first second (FEV1) greater than or equal to (\>=) 65 percent of predicted normal value at Screening Visit 2

Exclusion Criteria:

* Part 1 (healthy participants): Has any condition that in the opinion of the investigators, would constitute a risk or a contraindication for participating in the study, prevent the participant from meeting or performing study requirements, or could interfere with the study objectives, conduct, or evaluation
* At Screening Visit 1 and throughout the study, works with (or lives with a family member who cares for) the elderly, (eg, nursing home), or lives with someone who may be at risk from transmission of the human rhinovirus type 16 (HRV-16) challenge agent, including, but not limited to, individuals with chronic lung disease (including asthma), a premature infant, or an immunocompromised individual
* Has had any acute illness, including a common cold, within 4 weeks prior to Screening Visit 1, or has had a major illness or hospitalization within 6 months prior to Screening Visit 1
* Has active allergic rhinitis or perennial allergy symptoms (eg, due to ragweed) at Screening Visit 2 or expects to have active allergic rhinitis or perennial allergy symptoms during the study
* Has a current infection (eg, sepsis, pneumonia or pyelonephritis), or has been hospitalized and/or received antimicrobials for a serious infection during the 6 months prior to Screening Visit 1
* Part 2 (asthmatic patients): Has a history of any other chronic lung disease, including chronic obstructive pulmonary disease (COPD), bronchiolitis, bronchiectasis, allergic bronchopulmonary aspergillosis (mycosis), occupational asthma, sleep apnea, pulmonary hypertension, or any other obstructive pulmonary disease, liver or renal insufficiency; significant unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, or other body system disorders that are clinically significant in the opinion of the investigator
* Has ever had an episode of life-threatening asthma defined as respiratory arrest or requiring intubation for asthma
* Has been hospitalized (for greater than 24 hours) due to asthma in the 5 years prior to Screening Visit 1
* Has experienced an asthma exacerbation in the 12 weeks prior to Screening Visit 1 requiring management with systemic steroids
* Is receiving a high-dose inhaled corticosteroid (ICS) (\>500 µg/day to fluticasone or equivalent). Use of low or medium dose ICS (≤500 µg/day fluticasone or equivalent) with or without permitted controller medications, eg, long-acting Beta2 agonists (LABA), leukotriene receptor antagonists (LTRA), is allowed

Primary outcomes:
measure: The maximum percent decrease relative to baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) measurements (Part 2)
timeFrame: Up to 10 days after inoculation with human rhinovirus type 16 (HRV-16)
Secondary outcomes:
measure: Area under the serum concentration versus time curve (AUC) of change from baseline in Cold Symptom Assessment Score
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of change from baseline in Cold and Chest Symptom Scale
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of change from baseline in log-transformed fractional concentration of exhaled nitric oxide (FENO)
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of the percent change from baseline in clinic assessed prebronchodilator FEV1
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of change from baseline in morning (AM) peak expiratory flow rate (PEFR)
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of the change from baseline in prebronchodilator percent predicted FEV1
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of the change from baseline in prebronchodilator forced vital capacity (FVC)
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of the change from baseline in prebronchodilator forced expiratory flow at 25 to 75% of vital capacity (FEV25-75)
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of the change from baseline in prebronchodilator FEV1/FVC
timeFrame: Up to 10 days after inoculation with HRV-16
measure: AUC of change from baseline in average total asthma symptom diary score
timeFrame: Up to 10 days after inoculation with HRV-16
measure: Change from baseline in Asthma Control Questionnaire (ACQ)
timeFrame: Up to 10 days after inoculation with HRV-16
measure: Change from baseline in Cold Symptom Assessment Score
timeFrame: Up to 11 weeks
measure: Change from baseline in Cold and Chest Symptom Scale
timeFrame: Up to 11 weeks
measure: Change from baseline in log-transformed FENO over time
timeFrame: Up to 11 weeks
measure: Change from baseline over time in prebronchodilator and postbronchodilator FEV1
timeFrame: Up to 11 weeks
measure: Change from baseline over time in percent-predicted prebronchodilator and postbronchodilator FEV1
timeFrame: Up to 11 weeks
measure: Change from baseline over time in prebronchodilator and postbronchodilator FVC
timeFrame: Up to 11 weeks
measure: Change from baseline over time in prebronchodilator and postbronchodilator FEV25-75
timeFrame: Up to 11 weeks
measure: Change from baseline over time in prebronchodilator and postbronchodilator FEV1/FVC
timeFrame: Up to 11 weeks
measure: Change from baseline in morning/evening PEFR over time
timeFrame: Up to 11 weeks
measure: Change from baseline in Total Nasal and Ocular Symptom Score (TNOSS)
timeFrame: Up to Day 22
measure: Change from baseline in average total asthma symptom diary score
timeFrame: Up to 11 weeks
measure: Change from baseline in average number of nocturnal awakenings
timeFrame: Up to 11 weeks
measure: Change from baseline in average rescue medication use over time
timeFrame: Up to 11 weeks
measure: Number of symptom-free days
timeFrame: Up to 10 days after inoculation with HRV-16
measure: The maximum decrease from baseline in the prebronchodilator FEV1 measurements
timeFrame: Up to 10 days after inoculation with HRV-16
measure: Time to the maximum decrease relative to baseline in prebronchodilator FEV1
timeFrame: Up to 10 days after inoculation with HRV-16
Other outcomes:
Locations:
city: Antwerp
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Halifax
country: Canada
state: Nova Scotia
city: Hellerup
country: Denmark
city: Kobenhavn Nv
country: Denmark
city: Borstel
country: Germany
city: Frankfurt
country: Germany
city: Amsterdam Zuidoost
country: Netherlands
city: Groningen
country: Netherlands
city: Belfast
country: United Kingdom
city: Dundee
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Silkoff PE, Flavin S, Gordon R, Loza MJ, Sterk PJ, Lutter R, Diamant Z, Turner RB, Lipworth BJ, Proud D, Singh D, Eich A, Backer V, Gern JE, Herzmann C, Halperin SA, Mensinga TT, Del Vecchio AM, Branigan P, San Mateo L, Baribaud F, Barnathan ES, Johnston SL. Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations: A randomized controlled study. J Allergy Clin Immunol. 2018 Apr;141(4):1220-1230. doi: 10.1016/j.jaci.2017.06.027. Epub 2017 Jul 20.