Trial Outcomes & Findings for Treatment With Omalizumab to Improve the Asthmatic Response to Rhinovirus Experimental Infection With Rhinovirus (NCT NCT02388997)

Last Updated: 2018-07-09

Results Overview

The primary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

4 days

Results posted on

2018-07-09

Participant Flow

Participant milestones

Participant milestones
Measure	Mild Asthmatics Treated With Omalizumab Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Overall Study STARTED	15	16
Overall Study COMPLETED	12	10
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Mild Asthmatics Treated With Omalizumab Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	2	1
Overall Study Lung function exclusion criteria	0	2
Overall Study Tested positive for virus during run-in	0	1

Baseline Characteristics

Treatment With Omalizumab to Improve the Asthmatic Response to Rhinovirus Experimental Infection With Rhinovirus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mild Asthmatics Treated With Omalizumab n=15 Participants Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=16 Participants Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Total n=31 Participants Total of all reporting groups
Age, Continuous	20.4 years n=5 Participants	22.8 years n=7 Participants	21.6 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Total serum IgE level (IU/ml)	238 IU/ml n=5 Participants	266 IU/ml n=7 Participants	252 IU/ml n=5 Participants
Negative serum neutralizing antibody to rhinovirus-16	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 days

Population: Two participants in the mild asthmatics treated with omalizumab treatment arm had to be dropped according to protocol because one developed a positive qPCR test for rhinovirus (the virus used for inoculation) 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation.

Outcome measures

Outcome measures
Measure	Mild Asthmatics Treated With Omalizumab n=10 Participants Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=10 Participants Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection.	4.0 units on a scale Interval 0.0 to 5.0	3.3 units on a scale Interval 0.0 to 7.4

SECONDARY outcome

Timeframe: 7 days

This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 7 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18.

Outcome measures

Outcome measures
Measure	Mild Asthmatics Treated With Omalizumab n=10 Participants Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=10 Participants Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Airway Symptom Scores Experienced by Participants During the First 7 Days of the Acute Infection.	5.0 units on a scale Interval 0.0 to 12.8	8.4 units on a scale Interval 0.0 to 18.4

SECONDARY outcome

Timeframe: 21 days

This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the 21 days of monitoring during the infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18.

Outcome measures

Outcome measures
Measure	Mild Asthmatics Treated With Omalizumab n=10 Participants Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=10 Participants Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Airway Symptom Scores Experienced by Participants During the 21 Days of Monitoring During the Infection.	19.9 units on a scale Interval 0.0 to 49.7	17.0 units on a scale Interval 0.0 to 41.0

SECONDARY outcome

Timeframe: 4 days

This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, shortness of breath and cough. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 24. The scores recorded daily could range from 0 to 24.

Outcome measures

Outcome measures
Measure	Mild Asthmatics Treated With Omalizumab n=10 Participants Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=10 Participants Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection With Cough.	3.7 units on a scale Interval 0.0 to 7.5	5.3 units on a scale Interval 0.7 to 9.9

SECONDARY outcome

Timeframe: 4 days

This secondary outcome was based on the comparison of cumulative upper respiratory tract symptoms scores (CURTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included runny nose, sneezing, nasal congestion, sore throat, headache, chills/fever, fatigue, itchy/watery eyes. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 48. The scores recorded daily could range from 0 to 48.

Outcome measures

Outcome measures
Measure	Mild Asthmatics Treated With Omalizumab n=10 Participants Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=10 Participants Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection (Upper Respiratory Tract Symptoms).	20.2 units on a scale Interval 7.2 to 33.2	27.9 units on a scale Interval 17.1 to 38.7

SECONDARY outcome

Timeframe: 21 days

Population: Two participants in the omalizumab treatment arm had to be dropped according to protocol because 1 developed a positive qPCR test for rhinovirus 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation.

Number of participants whose FEV1 dropped by more than 20% during the infection compared to their FEV1 value at baseline at the time of enrollment.

Outcome measures

Outcome measures
Measure	Mild Asthmatics Treated With Omalizumab n=10 Participants Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=10 Participants Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Number of Participants Whose FEV1 Dropped by More Than 20% During the Infection.	0 Participants	0 Participants

POST_HOC outcome

Timeframe: 21 days

Time to peak airway symptoms (lower respiratory tract) following virus inoculation was compared among the asthmatics in the omalizumab treatment arm compared to time to peak symptoms among those in the placebo treatment arm.

Outcome measures

Outcome measures
Measure	Mild Asthmatics Treated With Omalizumab n=10 Participants Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=10 Participants Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Time to Peak Airway Symptoms (Lower Respiratory Tract) Following Virus Inoculation.	16.0 days Interval 12.74 to 20.09	7.77 days Interval 4.61 to 13.07

Adverse Events

Mild Asthmatics Treated With Omalizumab

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Mild Asthmatics Treated With Placebo Medication

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Mild Asthmatics Treated With Omalizumab n=15 participants at risk Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.	Mild Asthmatics Treated With Placebo Medication n=16 participants at risk Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Respiratory, thoracic and mediastinal disorders allergic rhinitis with hoarse voice	6.7% 1/15 • Number of events 1 • 12 weeks	0.00% 0/16 • 12 weeks
Respiratory, thoracic and mediastinal disorders Laryngitis	6.7% 1/15 • Number of events 1 • 12 weeks	0.00% 0/16 • 12 weeks
Blood and lymphatic system disorders Anemia (low hemoglobin)	6.7% 1/15 • Number of events 1 • 12 weeks	12.5% 2/16 • Number of events 2 • 12 weeks
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/15 • 12 weeks	6.2% 1/16 • Number of events 1 • 12 weeks
General disorders Insomnia	6.7% 1/15 • Number of events 3 • 12 weeks	0.00% 0/16 • 12 weeks
Injury, poisoning and procedural complications Mild concusion	0.00% 0/15 • 12 weeks	6.2% 1/16 • Number of events 1 • 12 weeks
Blood and lymphatic system disorders Blood neutropenia	6.7% 1/15 • Number of events 2 • 12 weeks	0.00% 0/16 • 12 weeks

Additional Information

Peter W. Heymann

University of Virginia

Phone: 434-982-3654

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place