Trial Outcomes & Findings for A Prospective, Randomized, Double-Blind Study of the Efficacy of Omalizumab (Xolair) in Atopic Asthmatics With Good Lung Capacity Who Remain Difficult to Treat (EXACT) (NCT NCT00096954)
NCT ID: NCT00096954
Last Updated: 2017-06-14
Results Overview
A protocol-defined asthma exacerbation was a worsening of asthma requiring treatment with oral or intravenous corticosteroid burst and/or a doubling of the baseline inhaled corticosteroids (ICS) dose for at least 3 days. The rate of protocol-defined asthma exacerbations, normalized by subject-time at risk and computed over the 24 week treatment period in each treatment group.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
333 participants
Primary outcome timeframe
Start of treatment to 24 weeks
Results posted on
2017-06-14
Participant Flow
Participant milestones
| Measure |
Omalizumab (Xolair)
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
The dose of placebo consisting of sucrose, L-histidine, L-histidine hydrochloride monohydrate, and polysorbate 20 was administered by subcutaneous injection every 2 or 4 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
159
|
174
|
|
Overall Study
Received Study Drug
|
157
|
171
|
|
Overall Study
COMPLETED
|
135
|
154
|
|
Overall Study
NOT COMPLETED
|
24
|
20
|
Reasons for withdrawal
| Measure |
Omalizumab (Xolair)
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
The dose of placebo consisting of sucrose, L-histidine, L-histidine hydrochloride monohydrate, and polysorbate 20 was administered by subcutaneous injection every 2 or 4 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
9
|
8
|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Sponsors Decision
|
1
|
1
|
|
Overall Study
Pregnancy
|
1
|
1
|
|
Overall Study
Initiation of immunotherapy
|
1
|
0
|
|
Overall Study
Non-compliance
|
0
|
3
|
|
Overall Study
Lost to Follow-up
|
8
|
5
|
Baseline Characteristics
A Prospective, Randomized, Double-Blind Study of the Efficacy of Omalizumab (Xolair) in Atopic Asthmatics With Good Lung Capacity Who Remain Difficult to Treat (EXACT)
Baseline characteristics by cohort
| Measure |
Omalizumab (Xolair)
n=157 Participants
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
n=171 Participants
The dose of placebo was administered by subcutaneous injection every 2 or 4 weeks.
|
Total
n=328 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.0 years
STANDARD_DEVIATION 14.7 • n=5 Participants
|
38.1 years
STANDARD_DEVIATION 15.1 • n=7 Participants
|
37.1 years
STANDARD_DEVIATION 14.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
110 Participants
n=5 Participants
|
116 Participants
n=7 Participants
|
226 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
102 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Start of treatment to 24 weeksPopulation: Modified Intent-to-Treat - All randomly assigned patients who received at least 1 dose of study drug (omalizumab or placebo).
A protocol-defined asthma exacerbation was a worsening of asthma requiring treatment with oral or intravenous corticosteroid burst and/or a doubling of the baseline inhaled corticosteroids (ICS) dose for at least 3 days. The rate of protocol-defined asthma exacerbations, normalized by subject-time at risk and computed over the 24 week treatment period in each treatment group.
Outcome measures
| Measure |
Omalizumab (Xolair)
n=157 Participants
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
n=171 Participants
The dose of placebo was administered by subcutaneous injection every 2 or 4 weeks.
|
|---|---|---|
|
Rate of Asthma Exacerbations Over the 24 Week Treatment Period
|
0.205 exacerbations per 24 patient-week period
|
0.258 exacerbations per 24 patient-week period
|
SECONDARY outcome
Timeframe: Start of treatment to 24 weeksPopulation: Modified Intent-to-Treat - All randomly assigned patients who received at least 1 dose of study drug (omalizumab or placebo).
The number of patients reporting one or more protocol-defined asthma exacerbations during the 24 week treatment period. A protocol-defined asthma exacerbation was a worsening of asthma requiring treatment with oral or intravenous corticosteroid burst and/or a doubling of the baseline inhaled corticosteroids (ICS) dose for at least 3 days.
Outcome measures
| Measure |
Omalizumab (Xolair)
n=157 Participants
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
n=171 Participants
The dose of placebo was administered by subcutaneous injection every 2 or 4 weeks.
|
|---|---|---|
|
Number of Participants Experiencing One or More Protocol-defined Asthma Exacerbations During the Treatment Period
|
24 participants
|
33 participants
|
SECONDARY outcome
Timeframe: Baseline and 24 weeksPopulation: Modified Intent-to-Treat. Patients with missing Asthma Symptom Score data at week 24 were excluded.
The daytime asthma symptom score assessed the symptoms: shortness of breath, chest discomfort, wheezing, and cough over the previous 24 hour period on a scale of 0(no symptoms) to 4(marked discomfort). The nocturnal asthma score was the patient's response to:How did you sleep last night? rated on a scale of 0(no problems) to 4(difficulty sleeping;rescue medicine used). Scores were collected daily. Change from Baseline (mean of last 28 days prior to first dosing date) at Week 24 (mean of last 28 days prior to week 24 visit). A negative change from baseline score indicates improvement.
Outcome measures
| Measure |
Omalizumab (Xolair)
n=132 Participants
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
n=154 Participants
The dose of placebo was administered by subcutaneous injection every 2 or 4 weeks.
|
|---|---|---|
|
Change From Baseline in Nocturnal and Daytime Asthma Symptom Scores at Week 24
Daytime
|
-0.73 score on a scale
Standard Deviation 0.72
|
-0.67 score on a scale
Standard Deviation 0.72
|
|
Change From Baseline in Nocturnal and Daytime Asthma Symptom Scores at Week 24
Nocturnal
|
-0.48 score on a scale
Standard Deviation 0.77
|
-0.49 score on a scale
Standard Deviation 0.67
|
SECONDARY outcome
Timeframe: Baseline and 24 weeksPopulation: Modified Intent-to-Treat. Patients with missing FEV1 data at either baseline or week 24 were excluded.
Spirometry was used to assess FEV1. All spirometry measurements were performed in accordance with the American Thoracic Society (ATS) guidelines. The relative percent change from baseline in forced expiratory volume (liters) in one second (FEV1) was calculated at week 24 using the formula: (FEV1 at week 24 - FEV1 at baseline) / FEV1 at baseline \* 100 for each treatment group.
Outcome measures
| Measure |
Omalizumab (Xolair)
n=135 Participants
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
n=153 Participants
The dose of placebo was administered by subcutaneous injection every 2 or 4 weeks.
|
|---|---|---|
|
Relative Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 24
|
4.15 percent change
Standard Deviation 21.53 • Interval 1.23 to 8.39
|
-0.75 percent change
Standard Deviation 11.90 • Interval 1.23 to 8.39
|
Adverse Events
Omalizumab (Xolair)
Serious events: 4 serious events
Other events: 36 other events
Deaths: 0 deaths
Placebo
Serious events: 6 serious events
Other events: 56 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Omalizumab (Xolair)
n=157 participants at risk
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
n=171 participants at risk
The dose of placebo was administered by subcutaneous injection every 2 or 4 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Esophageal perforation
|
0.64%
1/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.00%
0/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
General disorders
Chest pain
|
0.00%
0/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.58%
1/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.58%
1/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Infections and infestations
Influenza
|
0.64%
1/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.00%
0/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.58%
1/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.64%
1/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.00%
0/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma
|
0.00%
0/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.58%
1/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Nervous system disorders
Cerebrovascular accident
|
0.64%
1/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.00%
0/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Nervous system disorders
Convulsion
|
0.64%
1/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.00%
0/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
1.2%
2/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.58%
1/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Surgical and medical procedures
Abortion induced
|
0.00%
0/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
0.58%
1/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
Other adverse events
| Measure |
Omalizumab (Xolair)
n=157 participants at risk
Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of \> 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
|
Placebo
n=171 participants at risk
The dose of placebo was administered by subcutaneous injection every 2 or 4 weeks.
|
|---|---|---|
|
Infections and infestations
upper respiratory tract infection
|
9.6%
15/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
9.9%
17/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Infections and infestations
sinusitis
|
7.0%
11/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
9.4%
16/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Infections and infestations
nasopharyngitis
|
5.7%
9/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
9.4%
16/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
|
Nervous system disorders
headache
|
4.5%
7/157 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
5.8%
10/171 • From first dosing date to 30 days after last dosing date, or the last day on study, whichever is earlier. (Up to 29.3 weeks)
|
Additional Information
Medical Communications
Hoffman-LaRoche
Phone: 800-821-8590
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER