Trial Outcomes & Findings for Study to Evaluate the Effect of Omalizumab on Improving the Tolerability of Specific Immunotherapy in Patients With Persistent Allergic Asthma (NCT NCT00267202)
NCT ID: NCT00267202
Last Updated: 2016-09-14
Results Overview
The number of participants with Systemic Allergic Reactions (SAR) to Specific Immunotherapy (SIT). A SAR was captured and recorded as an outcome, not as adverse events (AEs) or SAEs. The primary analysis time point was the end of Period 4 (maintenance immunotherapy). Participants were observed for 1 hour after each immunotherapy (IT) injection visit. Allergic reactions were graded on a 4-point scale from Grade 1 to Grade 4. Grade 1: Skin symptoms, Grade 2: Gastrointestinal symptoms, Grade 3: Respiratory symptoms and Grade 4: Cardiovascular symptoms.
COMPLETED
PHASE4
275 participants
26 Weeks
2016-09-14
Participant Flow
Participant milestones
| Measure |
Placebo
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Omalizumab
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
|---|---|---|
|
Overall Study
STARTED
|
136
|
139
|
|
Overall Study
COMPLETED
|
83
|
105
|
|
Overall Study
NOT COMPLETED
|
53
|
34
|
Reasons for withdrawal
| Measure |
Placebo
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Omalizumab
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
|---|---|---|
|
Overall Study
Unsatisfactory therapeutic effect
|
21
|
8
|
|
Overall Study
Withdrawal by Subject
|
12
|
15
|
|
Overall Study
Adverse Event
|
13
|
7
|
|
Overall Study
Protocol Violation
|
2
|
3
|
|
Overall Study
Administrative problems
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
3
|
0
|
Baseline Characteristics
Study to Evaluate the Effect of Omalizumab on Improving the Tolerability of Specific Immunotherapy in Patients With Persistent Allergic Asthma
Baseline characteristics by cohort
| Measure |
Placebo
n=136 Participants
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Omalizumab
n=139 Participants
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Total
n=275 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.2 years
STANDARD_DEVIATION 10.02 • n=39 Participants
|
38.2 years
STANDARD_DEVIATION 9.89 • n=41 Participants
|
38.2 years
STANDARD_DEVIATION 9.93 • n=35 Participants
|
|
Sex: Female, Male
Female
|
99 Participants
n=39 Participants
|
88 Participants
n=41 Participants
|
187 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=39 Participants
|
51 Participants
n=41 Participants
|
88 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=39 Participants
|
1 participants
n=41 Participants
|
1 participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
11 participants
n=39 Participants
|
17 participants
n=41 Participants
|
28 participants
n=35 Participants
|
|
Race/Ethnicity, Customized
White
|
112 participants
n=39 Participants
|
118 participants
n=41 Participants
|
230 participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
13 participants
n=39 Participants
|
3 participants
n=41 Participants
|
16 participants
n=35 Participants
|
PRIMARY outcome
Timeframe: 26 WeeksPopulation: Efficacy Population: Consisted of all randomized patients who completed the omalizumab or placebo treatment period and received at least one dose of immunotherapy.
The number of participants with Systemic Allergic Reactions (SAR) to Specific Immunotherapy (SIT). A SAR was captured and recorded as an outcome, not as adverse events (AEs) or SAEs. The primary analysis time point was the end of Period 4 (maintenance immunotherapy). Participants were observed for 1 hour after each immunotherapy (IT) injection visit. Allergic reactions were graded on a 4-point scale from Grade 1 to Grade 4. Grade 1: Skin symptoms, Grade 2: Gastrointestinal symptoms, Grade 3: Respiratory symptoms and Grade 4: Cardiovascular symptoms.
Outcome measures
| Measure |
Placebo
n=122 Participants
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Omalizumab
n=126 Participants
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
All Patients
n=248 Participants
|
|---|---|---|---|
|
Number of Participants With Systemic Allergic Reactions (SAR) to Specific Immunotherapy (SIT)
|
32 participants
|
17 participants
|
49 participants
|
SECONDARY outcome
Timeframe: 26 WeeksPopulation: Efficacy population: Consisted of all randomized patients who completed the omalizumab or placebo treatment period and received at least one dose of immunotherapy.
Systemic reactions associated with immunotherapy (IT), defined as occurring within 1 hour following injection of SIT, were graded on a four-point scale: Grade 1: Skin symptoms (generalized urticaria, itching, or erythema), Grade 2: Gastrointestinal symptoms (stomach pain, nausea, or vomiting), Grade 3: Respiratory symptoms (clinically significant nasal symptoms and/or dyspnea, wheezing, persistent cough, etc.), Grade 4: Cardiovascular symptoms (cyanosis, hypotension, collapse, arrhythmias, or angina pectoris).
Outcome measures
| Measure |
Placebo
n=32 Participants
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Omalizumab
n=17 Participants
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
All Patients
n=49 Participants
|
|---|---|---|---|
|
Severity of First Systemic Allergic Reaction (SAR)
Grade 1 (skin symptoms)
|
6 participants
|
7 participants
|
13 participants
|
|
Severity of First Systemic Allergic Reaction (SAR)
Grade 2 (gastrointestinal symptoms)
|
0 participants
|
2 participants
|
2 participants
|
|
Severity of First Systemic Allergic Reaction (SAR)
Grade 3 (respiratory symptoms)
|
24 participants
|
6 participants
|
30 participants
|
|
Severity of First Systemic Allergic Reaction (SAR)
Grade 4 (cardiovascular symptoms)
|
2 participants
|
2 participants
|
4 participants
|
|
Severity of First Systemic Allergic Reaction (SAR)
No systemic allergy
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 16 WeeksPopulation: Efficacy population: Consisted of all randomized patients who completed the omalizumab or placebo treatment period and received at least one dose of immunotherapy.
Achievement of target maintenance IT dose is defined as answering 'Yes' to the question, 'Was the target maintenance SIT dose achieved?' on Visit 13, Week 16.
Outcome measures
| Measure |
Placebo
n=122 Participants
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Omalizumab
n=126 Participants
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
All Patients
n=248 Participants
|
|---|---|---|---|
|
Number of Participants Who Achieved Target Maintenance Specific Immunotherapy (SIT) Dose
|
88 participants
|
110 participants
|
198 participants
|
SECONDARY outcome
Timeframe: Up to 26 WeeksPopulation: Efficacy population: Consisted of all randomized patients who completed the omalizumab or placebo treatment period and received at least one dose of immunotherapy.
During period 3, a cluster dosing protocol was utilized to initiate the allergen immunotherapy (IT). Participants received escalating doses of IT according to a cluster dosing titration regimen. Visits 5 through 13 were cluster visits for this study. The number of visits needed for completion of the cluster SIT dosing regimen was defined as the number of planned visits plus the number of unplanned visits needed to reach maintenance IT dose.
Outcome measures
| Measure |
Placebo
n=122 Participants
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Omalizumab
n=126 Participants
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
All Patients
n=248 Participants
|
|---|---|---|---|
|
Number of Participants Requiring 8 to 20 Visits to Complete Cluster Specific Immunotherapy (SIT) Dosing Regimen
11 Visits
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants Requiring 8 to 20 Visits to Complete Cluster Specific Immunotherapy (SIT) Dosing Regimen
8 Visits
|
87 participants
|
110 participants
|
197 participants
|
|
Number of Participants Requiring 8 to 20 Visits to Complete Cluster Specific Immunotherapy (SIT) Dosing Regimen
9 Visits
|
35 participants
|
15 participants
|
50 participants
|
|
Number of Participants Requiring 8 to 20 Visits to Complete Cluster Specific Immunotherapy (SIT) Dosing Regimen
10 Visits
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Requiring 8 to 20 Visits to Complete Cluster Specific Immunotherapy (SIT) Dosing Regimen
12-20 Visits
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Up to 26 WeeksPopulation: Efficacy population: Consisted of all randomized participants who completed the omalizumab or placebo treatment period, received at least one dose of immunotherapy and received rescue therapy.
Epinephrine for injection, antihistamines, corticosteroids for injection, inhaled beta-agonists, and oral corticosteroids, as well as other drugs used for managing acute allergic reactions to SIT, were available during all study visits. One dose of rescue medication for SAR reactions was equivalent to 1 entry of the CRF page 'concomitant medications/significant non-drug therapies associated with immunotherapy' in response to the question 'Was this medication given in response to a SAR?'
Outcome measures
| Measure |
Placebo
n=32 Participants
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Omalizumab
n=17 Participants
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
All Patients
n=49 Participants
|
|---|---|---|---|
|
Number of Participants Requiring 0 to >=5 Doses of Rescue Medications for Systemic Allergic Reactions (SARs) to Specific Immunotherapy (SIT)
All rescue medications: 0 doses
|
2 participants
|
4 participants
|
6 participants
|
|
Number of Participants Requiring 0 to >=5 Doses of Rescue Medications for Systemic Allergic Reactions (SARs) to Specific Immunotherapy (SIT)
All rescue medications: 1 dose
|
10 participants
|
3 participants
|
13 participants
|
|
Number of Participants Requiring 0 to >=5 Doses of Rescue Medications for Systemic Allergic Reactions (SARs) to Specific Immunotherapy (SIT)
All rescue medications: 2 doses
|
5 participants
|
3 participants
|
8 participants
|
|
Number of Participants Requiring 0 to >=5 Doses of Rescue Medications for Systemic Allergic Reactions (SARs) to Specific Immunotherapy (SIT)
All rescue medications: 3 doses
|
4 participants
|
4 participants
|
8 participants
|
|
Number of Participants Requiring 0 to >=5 Doses of Rescue Medications for Systemic Allergic Reactions (SARs) to Specific Immunotherapy (SIT)
All rescue medications: 4 doses
|
5 participants
|
2 participants
|
7 participants
|
|
Number of Participants Requiring 0 to >=5 Doses of Rescue Medications for Systemic Allergic Reactions (SARs) to Specific Immunotherapy (SIT)
All rescue medications: >= 5 doses
|
6 participants
|
1 participants
|
7 participants
|
Adverse Events
Omalizumab
Placebo
Serious adverse events
| Measure |
Omalizumab
n=139 participants at risk
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Placebo
n=136 participants at risk
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
|---|---|---|
|
Gastrointestinal disorders
Swollen tongue
|
0.00%
0/139
|
0.74%
1/136
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/139
|
0.74%
1/136
|
|
Immune system disorders
Food allergy
|
0.00%
0/139
|
0.74%
1/136
|
|
Infections and infestations
Cellulitis staphylococcal
|
0.72%
1/139
|
0.00%
0/136
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of spinal cord
|
0.00%
0/139
|
0.74%
1/136
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.72%
1/139
|
0.00%
0/136
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/139
|
0.74%
1/136
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal oedema
|
0.00%
0/139
|
0.74%
1/136
|
|
Social circumstances
Sexual abuse
|
0.72%
1/139
|
0.00%
0/136
|
|
Surgical and medical procedures
Abortion induced
|
0.72%
1/139
|
0.00%
0/136
|
Other adverse events
| Measure |
Omalizumab
n=139 participants at risk
The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
Placebo
n=136 participants at risk
The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
|
|---|---|---|
|
General disorders
Injection site erythema
|
14.4%
20/139
|
16.2%
22/136
|
|
General disorders
Injection site induration
|
5.8%
8/139
|
5.9%
8/136
|
|
General disorders
Injection site pruritus
|
13.7%
19/139
|
17.6%
24/136
|
|
General disorders
Injection site reaction
|
20.1%
28/139
|
14.7%
20/136
|
|
General disorders
Injection site swelling
|
10.1%
14/139
|
11.8%
16/136
|
|
General disorders
Injection site urticaria
|
6.5%
9/139
|
4.4%
6/136
|
|
Infections and infestations
Nasopharyngitis
|
11.5%
16/139
|
12.5%
17/136
|
|
Infections and infestations
Sinusitis
|
5.0%
7/139
|
9.6%
13/136
|
|
Infections and infestations
Upper respiratory tract infection
|
13.7%
19/139
|
10.3%
14/136
|
|
Infections and infestations
Viral upper respiratory tract infection
|
2.2%
3/139
|
5.1%
7/136
|
|
Nervous system disorders
Headache
|
5.0%
7/139
|
8.1%
11/136
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.72%
1/139
|
8.8%
12/136
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.3%
6/139
|
5.1%
7/136
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
7/139
|
2.9%
4/136
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER