Healthy Volunteers and Asthma Clinical Trial
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
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).
| Status | Completed |
| Enrollment | 76 |
| Est. completion date | November 2014 |
| Est. primary completion date | November 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 18 Years to 75 Years |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Janssen Research & Development, LLC |
Belgium, Canada, Denmark, Germany, Netherlands, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The maximum percent decrease relative to baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) measurements (Part 2) | Up to 10 days after inoculation with human rhinovirus type 16 (HRV-16) | No | |
| Secondary | Area under the serum concentration versus time curve (AUC) of change from baseline in Cold Symptom Assessment Score | Cold symptoms is rated using a 5 point scale (0=none and 4=very severe). Scores can range from 0-32, with higher scores indicating more symptoms. | Up to 10 days after inoculation with HRV-16 | No |
| Secondary | AUC of change from baseline in Cold and Chest Symptom Scale | Cold and chest symptoms are rated using a 5 point scale: 0 using a 5 point scale (0=none and 4=very severe). Scores can range from 0-60, with higher scores indicating more symptoms. | Up to 10 days after inoculation with HRV-16 | No |
| Secondary | AUC of change from baseline in log-transformed fractional concentration of exhaled nitric oxide (FENO) | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | AUC of the percent change from baseline in clinic assessed prebronchodilator FEV1 | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | AUC of change from baseline in morning (AM) peak expiratory flow rate (PEFR) | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | AUC of the change from baseline in prebronchodilator percent predicted FEV1 | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | AUC of the change from baseline in prebronchodilator forced vital capacity (FVC) | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | AUC of the change from baseline in prebronchodilator forced expiratory flow at 25 to 75% of vital capacity (FEV25-75) | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | AUC of the change from baseline in prebronchodilator FEV1/FVC | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | AUC of change from baseline in average total asthma symptom diary score | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | Change from baseline in Asthma Control Questionnaire (ACQ) | ACQ is an instrument designed to evaluate asthma control. Seven items are scored on a 7-point scale (0=good control, 6=poor control) with the mean score as an overall summary score. Questions 1-6 are completed by the patient; the last item is entered by site personnel and corresponds to the patient's percent predicted FEV1 categorized according to the 7-point scale. Higher scores reflect poorer control. | Up to 10 days after inoculation with HRV-16 | No |
| Secondary | Change from baseline in Cold Symptom Assessment Score | Clinical symptoms to HRV-16 will be assessed by using the Cold Symptom Assessment Score, wherein participants will report the presence and severity of their cold symptoms in the context of the previous 24 hours via an interactive interview with the study staff. The symptoms consist of nasal congestion (stuffy nose), rhinorrhea (runny nose), sore throat, sneezing, cough, headache, malaise (feeling run down, tired) and chilliness. Severity is rated using a 5 point scale (0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe). Scores can range from 0-32, with higher scores indicating more symptoms. | Up to 11 weeks | No |
| Secondary | Change from baseline in Cold and Chest Symptom Scale | The Cold and Chest Symptom Scale contains 15 items composing 2 domains, a total cold score and a total chest score. Together, these 2 domains comprise the chest symptom assessment score. Total Cold Score domain: sneezing, runny nose, blocked or stuff nose, sore throat or hoarse voice, headache or face pain, generally unwell, chills, fever or shivery and cough and Total Chest Score domain: cough on waking, wheeze on waking, daytime cough, daytime wheeze, daytime chest tightness, daytime breathlessness and nocturnal cough, wheeze and breathlessness. Severity is rated using a 5 point scale: 0 using a 5 point scale (0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe). Scores can range from 0-60, with higher scores indicating more symptoms. |
Up to 11 weeks | No |
| Secondary | Change from baseline in log-transformed FENO over time | Up to 11 weeks | No | |
| Secondary | Change from baseline over time in prebronchodilator and postbronchodilator FEV1 | Up to 11 weeks | No | |
| Secondary | Change from baseline over time in percent-predicted prebronchodilator and postbronchodilator FEV1 | Up to 11 weeks | No | |
| Secondary | Change from baseline over time in prebronchodilator and postbronchodilator FVC | Up to 11 weeks | No | |
| Secondary | Change from baseline over time in prebronchodilator and postbronchodilator FEV25-75 | Up to 11 weeks | No | |
| Secondary | Change from baseline over time in prebronchodilator and postbronchodilator FEV1/FVC | Up to 11 weeks | No | |
| Secondary | Change from baseline in morning/evening PEFR over time | Up to 11 weeks | No | |
| Secondary | Change from baseline in Total Nasal and Ocular Symptom Score (TNOSS) | Nose and eye symptoms are rated by the patient using a 5-point categorical response scale from 0 to 4, where 0 indicates absent/no symptom, and 4 indicates extremely severe symptoms, with a 24-hour recall period. | Up to Day 22 | No |
| Secondary | Change from baseline in average total asthma symptom diary score | Up to 11 weeks | No | |
| Secondary | Change from baseline in average number of nocturnal awakenings | Up to 11 weeks | No | |
| Secondary | Change from baseline in average rescue medication use over time | Up to 11 weeks | No | |
| Secondary | Number of symptom-free days | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | The maximum decrease from baseline in the prebronchodilator FEV1 measurements | Up to 10 days after inoculation with HRV-16 | No | |
| Secondary | Time to the maximum decrease relative to baseline in prebronchodilator FEV1 | Up to 10 days after inoculation with HRV-16 | No |