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A Study of CNTO 3157 in Healthy Normal and Asthmatic Participants Inoculated With Human Rhinovirus Type 16

Primary Purpose

Healthy Volunteers and Asthma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

CNTO 3157 (healthy participants)

Placebo (healthy participants)

CNTO 3157 (asthmatic patients)

Placebo (asthmatic patients)

HRV-16

About this trial

This is an interventional basic science trial for Healthy Volunteers and Asthma focused on measuring Healthy volunteers and asthma, CNTO 3157, Rhinovirus

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part 1: Healthy participants (CNTO 3157 + HRV-16)

Part 1: Healthy participants (placebo + HRV-16)

Part 2: Asthmatic patients (CNTO 3157 + HRV-16)

Part 2: Asthmatic patients (placebo + HRV-16)

Arm Description

Outcomes

Primary Outcome Measures

The maximum percent decrease relative to baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) measurements (Part 2)

Secondary Outcome Measures

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.

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.

AUC of change from baseline in log-transformed fractional concentration of exhaled nitric oxide (FENO)

AUC of the percent change from baseline in clinic assessed prebronchodilator FEV1

AUC of change from baseline in morning (AM) peak expiratory flow rate (PEFR)

AUC of the change from baseline in prebronchodilator percent predicted FEV1

AUC of the change from baseline in prebronchodilator forced vital capacity (FVC)

AUC of the change from baseline in prebronchodilator forced expiratory flow at 25 to 75% of vital capacity (FEV25-75)

AUC of the change from baseline in prebronchodilator FEV1/FVC

AUC of change from baseline in average total asthma symptom diary score

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.

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.

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.

Change from baseline in log-transformed FENO over time

Change from baseline over time in prebronchodilator and postbronchodilator FEV1

Change from baseline over time in percent-predicted prebronchodilator and postbronchodilator FEV1

Change from baseline over time in prebronchodilator and postbronchodilator FVC

Change from baseline over time in prebronchodilator and postbronchodilator FEV25-75

Change from baseline over time in prebronchodilator and postbronchodilator FEV1/FVC

Change from baseline in morning/evening PEFR over time

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.

Change from baseline in average total asthma symptom diary score

Change from baseline in average number of nocturnal awakenings

Change from baseline in average rescue medication use over time

Number of symptom-free days

The maximum decrease from baseline in the prebronchodilator FEV1 measurements

Time to the maximum decrease relative to baseline in prebronchodilator FEV1

Full Information

NCT ID

NCT01704040

First Posted

October 8, 2012

Last Updated

December 11, 2014

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT01704040

Brief Title

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

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Completed

Study Start Date

October 2012 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy Volunteers and Asthma

Keywords

Healthy volunteers and asthma, CNTO 3157, Rhinovirus

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

76 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Healthy participants (CNTO 3157 + HRV-16)

Arm Type

Experimental

Arm Title

Part 1: Healthy participants (placebo + HRV-16)

Arm Type

Placebo Comparator

Arm Title

Part 2: Asthmatic patients (CNTO 3157 + HRV-16)

Arm Type

Experimental

Arm Title

Part 2: Asthmatic patients (placebo + HRV-16)

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

CNTO 3157 (healthy participants)

Intervention Description

CNTO 3157 10 mg/kg, as a single intravenous infusion, on Day 1, 24 to 72 hours prior to inoculation with human rhinovirus type 16 (HRV-16).

Intervention Type

Drug

Intervention Name(s)

Placebo (healthy participants)

Intervention Description

Placebo, as a single intravenous infusion, on Day 1, 24 to 72 hours prior to inoculation with HRV-16.

Intervention Type

Drug

Intervention Name(s)

CNTO 3157 (asthmatic patients)

Intervention Description

CNTO 3157 10 mg/kg, as a single intravenous infusion, at Week 1 (Day 1), followed by 3 infusions of 3 mg/kg of CNTO 3157 at Week 2 (Day 8), Week 3 (Day 15), and Week 4 (Day 22). The final infusion (Week 4) will occur 24 to 72 hours prior to inoculation with HRV-16.

Intervention Type

Drug

Intervention Name(s)

Placebo (asthmatic patients)

Intervention Description

Placebo, as 4 intravenous infusions, at Week 1 (Day 1), Week 2 (Day 8), Week 3 (Day 15), and Week 4 (Day 22). The final infusion (Week 4) will occur 24 to 72 hours prior to inoculation with HRV-16.

Intervention Type

Other

Intervention Name(s)

HRV-16

Intervention Description

Single inoculation of HRV-16 in a total volume of approximately 1.0 mL, administered as 2 instillations per naris.

Primary Outcome Measure Information:

Title

The maximum percent decrease relative to baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) measurements (Part 2)

Time Frame

Up to 10 days after inoculation with human rhinovirus type 16 (HRV-16)

Secondary Outcome Measure Information:

Title

Area under the serum concentration versus time curve (AUC) of change from baseline in Cold Symptom Assessment Score

Description

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.

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of change from baseline in Cold and Chest Symptom Scale

Description

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.

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of change from baseline in log-transformed fractional concentration of exhaled nitric oxide (FENO)

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of the percent change from baseline in clinic assessed prebronchodilator FEV1

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of change from baseline in morning (AM) peak expiratory flow rate (PEFR)

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of the change from baseline in prebronchodilator percent predicted FEV1

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of the change from baseline in prebronchodilator forced vital capacity (FVC)

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of the change from baseline in prebronchodilator forced expiratory flow at 25 to 75% of vital capacity (FEV25-75)

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of the change from baseline in prebronchodilator FEV1/FVC

Time Frame

Up to 10 days after inoculation with HRV-16

Title

AUC of change from baseline in average total asthma symptom diary score

Time Frame

Up to 10 days after inoculation with HRV-16

Title

Change from baseline in Asthma Control Questionnaire (ACQ)

Description

Time Frame

Up to 10 days after inoculation with HRV-16

Title

Change from baseline in Cold Symptom Assessment Score

Description

Time Frame

Up to 11 weeks

Title

Change from baseline in Cold and Chest Symptom Scale

Description

Time Frame

Up to 11 weeks

Title

Change from baseline in log-transformed FENO over time

Time Frame

Up to 11 weeks

Title

Change from baseline over time in prebronchodilator and postbronchodilator FEV1

Time Frame

Up to 11 weeks

Title

Change from baseline over time in percent-predicted prebronchodilator and postbronchodilator FEV1

Time Frame

Up to 11 weeks

Title

Change from baseline over time in prebronchodilator and postbronchodilator FVC

Time Frame

Up to 11 weeks

Title

Change from baseline over time in prebronchodilator and postbronchodilator FEV25-75

Time Frame

Up to 11 weeks

Title

Change from baseline over time in prebronchodilator and postbronchodilator FEV1/FVC

Time Frame

Up to 11 weeks

Title

Change from baseline in morning/evening PEFR over time

Time Frame

Up to 11 weeks

Title

Change from baseline in Total Nasal and Ocular Symptom Score (TNOSS)

Description

Time Frame

Up to Day 22

Title

Change from baseline in average total asthma symptom diary score

Time Frame

Up to 11 weeks

Title

Change from baseline in average number of nocturnal awakenings

Time Frame

Up to 11 weeks

Title

Change from baseline in average rescue medication use over time

Time Frame

Up to 11 weeks

Title

Number of symptom-free days

Time Frame

Up to 10 days after inoculation with HRV-16

Title

The maximum decrease from baseline in the prebronchodilator FEV1 measurements

Time Frame

Up to 10 days after inoculation with HRV-16

Title

Time to the maximum decrease relative to baseline in prebronchodilator FEV1

Time Frame

Up to 10 days after inoculation with HRV-16

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

City

Antwerp

Country

Belgium

City

Calgary

State/Province

Alberta

Country

Canada

City

Halifax

State/Province

Nova Scotia

Country

Canada

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

12. IPD Sharing Statement

Citations:

PubMed Identifier

28734844

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.

Results Reference

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A Study of CNTO 3157 in Healthy Normal and Asthmatic Participants Inoculated With Human Rhinovirus Type 16

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