Seasonal Allergic Rhinitis
Conditions
Keywords
cryptomeria, omalizumab, seasonal allergic rhinitis
Brief summary
The purpose of this study was to demonstrate the efficacy and safety of omalizumab compared with placebo, on top of SoC (anti-histamine and nasal corticosteroid) in adult and adolescent patients with severe Japanese cedar pollinosis, whose symptoms were inadequately controlled despite the current recommended therapies (nasal corticosteroids plus one or more medications out of anti-histamine, leukotriene receptor antagonist, or prostaglandin D2/thromboxane A2 receptor antagonist) in the previous 2 Japanese cedar pollen seasons.
Interventions
DRUGOmalizumab
Omalizumab were administered by subcutaneous injection. Dose (75 to 600 mg) and dosing frequency (every 2 or 4 weeks) were determined by serum total IgE level (IU/mL) and body weight (kg) measured at the screening epoch according the dosing table.
DRUGPlacebo
Placebo were administered by subcutaneous injection. Dose (75 to 600 mg) and dosing frequency (every 2 or 4 weeks) were determined by serum total IgE level (IU/mL) and body weight (kg) measured at the screening epoch according the dosing table.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* A clinical history of Japanese cedar pollinosis defined by the following * Took nasal corticosteroid plus one or more medications out of antihistamine (second generation), leukotriene receptor antagonist, or prostaglandin D2 thromboxane A2 receptor antagonist in Japanese cedar pollen seasons in 2016 and 2017. * Had inadequately controlled symptoms of Japanese cedar pollinosis lasting at least one week in the Japanese cedar pollen season in 2017 despite the nasal corticosteroid plus one or more medications out of anti-histamine (second generation), leukotriene receptor antagonist, or prostaglandin D2/thromboxane A2 receptor antagonist (regardless of having perennial allergic rhinitis or not) * Serum cedar pollen-specific Immunoglobulin E (IgE) levels of ≥ score of 3 by CAP/RAST-FEIA, ImmunoCAP or MAST at the screening epoch. * Developing a symptom of Japanese cedar pollinosis during the period from first observational day in cedar pollen in Kanto area to initial drug administration (Visit 101), as defined by the following * Having any nasal or ocular symptom (≥ score of 1 in sneezing, rhinorrhea, nasal congestion, itchy eye or watery eye) in at least 2 days or * Having both any nasal symptom (≥ score of 1 in sneezing, rhinorrhea, nasal congestion) and any eye symptom (≥ score of 1 in itchy eye or watery eye) in at least one day, which is confirmed by patient e-diary (unless a symptom is clearly consider to take place due to other than Japanese cedar pollinosis/allergic rhinitis (e.g., upper respiratory tract infection, or common cold)). * Body weight and serum total IgE level at screen epoch within the dosing table range; body weight of ≥ 20 to ≤ 150 kg and serum total IgE levels of ≥ 30 to ≤ 1500 IU/mL at a maximum.
Exclusion criteria
* With an active rhinitis other than allergic rhinitis (e.g acute or chronic rhinitis, idiopathic rhinitis). * With an active nose disease other than allergic rhinitis (e.g., acute or chronic rhinosinusitis or deflected septum) which is expected to affect the evaluation of efficacy of the study drug judged by the investigator. * With elevated serum IgE levels for reasons other than allergy (e.g., parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich Syndrome or clinical allergic bronchopulmonary aspergillosis). * With a severe asthma treated with high dose inhaled corticosteroid (≥ 800 μg/day fluticasone propionate or an equivalent for aged ≥ 16 to \<75 years, \> 200 μg/day for aged ≥ 12 to \<16 years). * Who are receiving operative treatment for allergic rhinitis (e.g., electrocoagulation, laser surgery, 80% trichloroacetic acid chemo-surgery, inferior turbinectomy or posterior nasal neurectomy) within 1 years prior to the screening epoch.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Nasal Symptom Score | Severe symptom period (from 23Feb2018 to 24March2018) | Nasal symptoms (sneezing, rhinorrhea and nasal congestion) were recorded by the patient everyday in their e-Diary, on a scale of 0 (none) to 4 (intense/severe). Nasal symptom score (0-12 point) consisted of score for severity of sneezing (0-4 point), rhinorrhea (0-4 point) and nasal congestion (0-4 point). Severe symptom period: The three weeks where the cumulative value of the mean daily nasal symptom score is the maximum. The three weeks must also meet one of the following criteria: 2) ≥ 70% of the period with concomitant use of fluticasone propionate is included in this three weeks. 2) ≥ 70% of this three weeks includes the period with concomitant use of fluticasone propionate. If not, severe symptom period was extended at a minimum to meet one of the criteria above. The severe symptom period will be defined as: the three weeks where the cumulative value of the mean daily nasal symptom score will be the maximum. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Nasal Symptom Medication Score, Mean Ocular Symptom Medication Score, and Mean Nasal Ocular Symptom Medication Score | Severe symptom period (from 23Feb2018 to 24Mar2018) | Medication scores were given for fluticasone propionate (nasal, 2 point), fexofenadine hydrochloride (oral, 1 point), tramazoline hydrochloride (nasal, 1 point), and levocabastine hydrochloride (ocular, 1 point). Symptom medication score consisted of severe symptom period. Nasal symptom medication score is the sum of nasal symptom score and medication score (fexofenadine hydrochloride, fluticasone propionate, tramazoline hydrochloride) Ocular symptom medication score is the sum of ocular symptom score and medication score (fexofenadine hydrochloride, levocabastine hydrochloride) Nasal ocular symptom medication score is the sum of nasal symptom score, ocular symptom score and medication score (fexofenadine hydrochloride, fluticasone propionate, tramazoline hydrochloride, levocabastine hydrochloride). |
| Mean Score for Severity of Sneezing, Rhinorrhea and Nasal Congestion | Severe symptom period (from 23Feb2018 to 24Mar2018) | Symptoms of sneezing, rhinorrhea and nasal congestion were evaluated on a scale of 0 (none) to 4 (intense/severe). |
| Mean Score for Severity of Itchy and Watery Eye | Severe symptom period (from 23Feb2018 to 24Mar2018) | Symptoms of itchy and watery eye were evaluated on a scale of 0 (none) to 4 (intense/severe). |
| Mean Score for Impairment of Daily Activities | Severe symptom period (from 23Feb2018 to 24Mar2018) | Impairment of daily activities were evaluated on a scale of 0 (none) to 4 (intense/severe). |
| Number of Symptom Free Days | Severe symptom period (from 23Feb2018 to 24March2018) | Nasal symptom free days (days with all nasal symptoms are not more than mild in severity) during the severe symptom period. Ocular symptom free days (days with all ocular symptoms are not more than mild in severity) during the severe symptom period. |
| Completely Nasal Symptom Free Patients | Severe symptom period (from 23Feb2018 to 24Mar2018) | Completely nasal symptom free patients is the number of patients who were nasal symptom free (all nasal symptoms were not more than mild in severity) on all non-missing days and had nasal symptom scores for at least 26 days during the 30 days of severe symptom period. |
| Mean Ocular Symptom Score and Mean Nasal Ocular Symptom Score | Severe symptom period (from 23Feb2018 to 24Mar2018) | Ocular symptoms (itchy and watery eye) were recorded by the patient everyday in their e-Diary, on a scale of 0 (none) to 4 (intense/severe). Ocular symptom score (0-8 point) consisted of score for severity of itchy eye (0-4 point) and watery eye (0-4 point). Nasal ocular symptom score consisted of nasal symptom score and ocular symptom score. Nasal ocular symptom score is the sum of nasal symptom score (0-12) and ocular symptom score (0-8) 0 presents no nasal ocular symptom and 20 presents worse outcome. |
| Rescue Medication Free Days | Severe symptom period (from 23Feb2018 to 24Mar2018) | Number of days with no rescue medication (tramazoline hydrochloride, levocabastine hydrochloride). Nasal ocular rescue medication free days were defined as the days with no use of tramazoline hydrochloride (nasal rescue medication) and levocabastine hydrochloride (ocular rescue medication). |
| Number of Rescue Medication Used | Severe symptom period (from 23Feb2018 to 24Mar2018) | Amount number of rescue medication used (a total number of times used). |
| Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ, No1) Score | Evaluation Visit, one visit during severe symptom period (23-Feb-2018 to 24-Mar-2018) for each patient | Nasal and eye symptoms (JRQLQ I) included 6 categories: Runny nose, Sneezing, Nasal congestion, Itchy nose, itchy eyes and watery eyes, on a 5-point scale of 0 to 4 (no symptoms to very severe symptoms). JRQLQ I score was a mean of these 6 categories. JRQLQ II included 17 items on a 5-point scale, 0 to 4 (no significant problem to very greatly). JRQLQ II scores was a mean of these 17 items. Overall face scale (JRQLQ III) evaluated overall symptoms, condition and feelings on a 5-point scale from 0 to 4 (fine to crying). Evaluation visit was defined as follows independently for each evaluation item and for each patient: 1) If there was a single visit during the severe symptom period, the visit was the evaluation visit. 2) If there were ≥ 2 visits during the severe symptom period and a) if Visit 105 was one of them, Visit 105 was the evaluation visit; b) if Visit 105 was outside the period, the closest visit to Visit 105 during the period was the evaluation visit. |
| Number of Participants With Anti-omalizumab Antibodes | Prior to first dosing (Day 1), At follow-up investigation which were conducted 20/22 weeks after 12 week-treatment epoch | Number of participants with antibodies against the Fab and Fc region of omalizumab in serum. |
| Serum Trough Omalizumab Concentration | Prior to first dosing (Day 1), at Day 29, Day 57, Day 85 and 24 weeks after last dose | Blood samples were collected Prior to first dosing (Day 1), at Day 29, Day 57, Day 85 and follow-up investigation which were conducted 20/22 weeks after 12 week-treatment epoch |
| Free IgE and Total IgE | Day 1, at Day 29, Day 57, Day 85 and 24 weeks after last dose | Blood samples were collected Prior to first dosing (Day 1), at Day 29, Day 57, Day 85 and follow-up investigation were conducted 20/22 weeks after 12 week-treatment epoch |
| Rescue Medication Score | Severe symptom period (from 23Feb2018 to 24Mar2018) | Rescue medication scores were given for tramazoline hydrochloride (nasal, 1 point) and levocabastine hydrochloride (ocular, 1 point). Rescue medication score for nasal is medication score for Tramazoline hydrochloride, Rescue medication score for ocular is medication score for Levocabastine hydrochloride and Rescue medication score for nasal and ocular is the sum of medication score for Tramazoline hydrochloride and Levocabastine hydrochlorid |
Countries
Japan
Participant flow
Recruitment details
This study was conducted at 22 centers in Kanto-area of Japan.
Pre-assignment details
337 patients were randomized
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab Omalizumab administered subcutaneously for 12 weeks | 162 |
| Placebo Placebo administered subcutaneously for 12 weeks | 175 |
| Total | 337 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Epoch | Lost to Follow-up | 1 | 0 |
| Treatment Epoch | Adverse Event | 2 | 0 |
| Treatment Epoch | Lack of Efficacy | 0 | 2 |
| Treatment Epoch | Lost to Follow-up | 0 | 1 |
| Treatment Epoch | Protocol Violation | 1 | 0 |
| Treatment Epoch | technical problems | 1 | 0 |
Baseline characteristics
| Characteristic | Omalizumab | Placebo | Total |
|---|---|---|---|
| Age, Customized 15 <=, < 65 years | 149 Participants | 158 Participants | 307 Participants |
| Age, Customized < 15 years | 4 Participants | 6 Participants | 10 Participants |
| Age, Customized >= 65 years | 9 Participants | 11 Participants | 20 Participants |
| Race/Ethnicity, Customized Asian | 162 Participants | 175 Participants | 337 Participants |
| Sex: Female, Male Female | 99 Participants | 97 Participants | 196 Participants |
| Sex: Female, Male Male | 63 Participants | 78 Participants | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 161 | 0 / 175 |
| other Total, other adverse events | 26 / 161 | 21 / 175 |
| serious Total, serious adverse events | 1 / 161 | 0 / 175 |
Outcome results
Primary
Mean Nasal Symptom Score
Nasal symptoms (sneezing, rhinorrhea and nasal congestion) were recorded by the patient everyday in their e-Diary, on a scale of 0 (none) to 4 (intense/severe). Nasal symptom score (0-12 point) consisted of score for severity of sneezing (0-4 point), rhinorrhea (0-4 point) and nasal congestion (0-4 point). Severe symptom period: The three weeks where the cumulative value of the mean daily nasal symptom score is the maximum. The three weeks must also meet one of the following criteria: 2) ≥ 70% of the period with concomitant use of fluticasone propionate is included in this three weeks. 2) ≥ 70% of this three weeks includes the period with concomitant use of fluticasone propionate. If not, severe symptom period was extended at a minimum to meet one of the criteria above. The severe symptom period will be defined as: the three weeks where the cumulative value of the mean daily nasal symptom score will be the maximum.
Time frame: Severe symptom period (from 23Feb2018 to 24March2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Mean Nasal Symptom Score | 3.66 score | Standard Error 0.151 |
| Placebo | Mean Nasal Symptom Score | 4.69 score | Standard Error 0.144 |
p-value: <0.00195% CI: [-1.44, -0.62]ANCOVA
Secondary
Completely Nasal Symptom Free Patients
Completely nasal symptom free patients is the number of patients who were nasal symptom free (all nasal symptoms were not more than mild in severity) on all non-missing days and had nasal symptom scores for at least 26 days during the 30 days of severe symptom period.
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omalizumab | Completely Nasal Symptom Free Patients | 13 Participants |
| Placebo | Completely Nasal Symptom Free Patients | 4 Participants |
p-value: 0.00595% CI: [1.21, 9.75]logistic regression
Secondary
Free IgE and Total IgE
Blood samples were collected Prior to first dosing (Day 1), at Day 29, Day 57, Day 85 and follow-up investigation were conducted 20/22 weeks after 12 week-treatment epoch
Time frame: Day 1, at Day 29, Day 57, Day 85 and 24 weeks after last dose
Population: Pharmacokinetic set (PK set): The PK set consisted of all randomized patients who received at least 1 dose of study drug and had at least 1 evaluable PK measurement. Patients in the PK set were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Free IgE and Total IgE | Free IgE (Day 57) | 20.8 ng/mL | Standard Deviation 10.1 |
| Omalizumab | Free IgE and Total IgE | Total IgE (Day 1 pre-dose) | 524 ng/mL | Standard Deviation 531 |
| Omalizumab | Free IgE and Total IgE | Free IgE (Day 29) | 21.3 ng/mL | Standard Deviation 9.8 |
| Omalizumab | Free IgE and Total IgE | Total IgE (Day 29) | 2040 ng/mL | Standard Deviation 1620 |
| Omalizumab | Free IgE and Total IgE | Free IgE (Day 85) | 18.6 ng/mL | Standard Deviation 11.9 |
| Omalizumab | Free IgE and Total IgE | Total IgE (Day 57) | 2160 ng/mL | Standard Deviation 1660 |
| Omalizumab | Free IgE and Total IgE | Total IgE (Day 85) | 1960 ng/mL | Standard Deviation 1480 |
| Omalizumab | Free IgE and Total IgE | Free IgE (Day 1 predose) | NA ng/mL | — |
| Omalizumab | Free IgE and Total IgE | Total IgE (Day 225/239) | 702 ng/mL | Standard Deviation 639 |
| Omalizumab | Free IgE and Total IgE | Free IgE (Day 225/239) | NA ng/mL | — |
| Placebo | Free IgE and Total IgE | Total IgE (Day 225/239) | 669 ng/mL | Standard Deviation 783 |
| Placebo | Free IgE and Total IgE | Free IgE (Day 1 predose) | NA ng/mL | — |
| Placebo | Free IgE and Total IgE | Free IgE (Day 29) | NA ng/mL | — |
| Placebo | Free IgE and Total IgE | Free IgE (Day 57) | NA ng/mL | — |
| Placebo | Free IgE and Total IgE | Free IgE (Day 85) | NA ng/mL | — |
| Placebo | Free IgE and Total IgE | Free IgE (Day 225/239) | NA ng/mL | — |
| Placebo | Free IgE and Total IgE | Total IgE (Day 1 pre-dose) | 570 ng/mL | Standard Deviation 641 |
| Placebo | Free IgE and Total IgE | Total IgE (Day 29) | 558 ng/mL | Standard Deviation 608 |
| Placebo | Free IgE and Total IgE | Total IgE (Day 85) | 673 ng/mL | Standard Deviation 775 |
| Placebo | Free IgE and Total IgE | Total IgE (Day 57) | 640 ng/mL | Standard Deviation 721 |
Secondary
Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ, No1) Score
Nasal and eye symptoms (JRQLQ I) included 6 categories: Runny nose, Sneezing, Nasal congestion, Itchy nose, itchy eyes and watery eyes, on a 5-point scale of 0 to 4 (no symptoms to very severe symptoms). JRQLQ I score was a mean of these 6 categories. JRQLQ II included 17 items on a 5-point scale, 0 to 4 (no significant problem to very greatly). JRQLQ II scores was a mean of these 17 items. Overall face scale (JRQLQ III) evaluated overall symptoms, condition and feelings on a 5-point scale from 0 to 4 (fine to crying). Evaluation visit was defined as follows independently for each evaluation item and for each patient: 1) If there was a single visit during the severe symptom period, the visit was the evaluation visit. 2) If there were ≥ 2 visits during the severe symptom period and a) if Visit 105 was one of them, Visit 105 was the evaluation visit; b) if Visit 105 was outside the period, the closest visit to Visit 105 during the period was the evaluation visit.
Time frame: Evaluation Visit, one visit during severe symptom period (23-Feb-2018 to 24-Mar-2018) for each patient
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ, No1) Score | Nasal and eye symptoms (JRQLQ I) | 1.27 Score | Standard Error 0.062 |
| Omalizumab | Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ, No1) Score | Mean score of QoL-related questionnaire (JRQLQ II) | 0.70 Score | Standard Error 0.067 |
| Omalizumab | Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ, No1) Score | Overall face scale (JRQLQ III) | 1.6 Score | Standard Error 0.08 |
| Placebo | Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ, No1) Score | Nasal and eye symptoms (JRQLQ I) | 1.76 Score | Standard Error 0.059 |
| Placebo | Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ, No1) Score | Mean score of QoL-related questionnaire (JRQLQ II) | 1.20 Score | Standard Error 0.064 |
| Placebo | Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ, No1) Score | Overall face scale (JRQLQ III) | 2.2 Score | Standard Error 0.07 |
95% CI: [-0.66, -0.33]
95% CI: [-0.69, -0.33]
95% CI: [-0.8, -0.4]
Secondary
Mean Nasal Symptom Medication Score, Mean Ocular Symptom Medication Score, and Mean Nasal Ocular Symptom Medication Score
Medication scores were given for fluticasone propionate (nasal, 2 point), fexofenadine hydrochloride (oral, 1 point), tramazoline hydrochloride (nasal, 1 point), and levocabastine hydrochloride (ocular, 1 point). Symptom medication score consisted of severe symptom period. Nasal symptom medication score is the sum of nasal symptom score and medication score (fexofenadine hydrochloride, fluticasone propionate, tramazoline hydrochloride) Ocular symptom medication score is the sum of ocular symptom score and medication score (fexofenadine hydrochloride, levocabastine hydrochloride) Nasal ocular symptom medication score is the sum of nasal symptom score, ocular symptom score and medication score (fexofenadine hydrochloride, fluticasone propionate, tramazoline hydrochloride, levocabastine hydrochloride).
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Mean Nasal Symptom Medication Score, Mean Ocular Symptom Medication Score, and Mean Nasal Ocular Symptom Medication Score | Mean nasal symptom medication score | 6.19 score | Standard Error 0.166 |
| Omalizumab | Mean Nasal Symptom Medication Score, Mean Ocular Symptom Medication Score, and Mean Nasal Ocular Symptom Medication Score | Mean ocular symptom medication score | 3.91 score | Standard Error 0.137 |
| Omalizumab | Mean Nasal Symptom Medication Score, Mean Ocular Symptom Medication Score, and Mean Nasal Ocular Symptom Medication Score | Mean nasal ocular symptom medication score | 9.10 score | Standard Error 0.271 |
| Placebo | Mean Nasal Symptom Medication Score, Mean Ocular Symptom Medication Score, and Mean Nasal Ocular Symptom Medication Score | Mean nasal symptom medication score | 7.29 score | Standard Error 0.158 |
| Placebo | Mean Nasal Symptom Medication Score, Mean Ocular Symptom Medication Score, and Mean Nasal Ocular Symptom Medication Score | Mean ocular symptom medication score | 4.86 score | Standard Error 0.13 |
| Placebo | Mean Nasal Symptom Medication Score, Mean Ocular Symptom Medication Score, and Mean Nasal Ocular Symptom Medication Score | Mean nasal ocular symptom medication score | 11.15 score | Standard Error 0.259 |
95% CI: [-1.55, -0.64]
95% CI: [-1.32, -0.58]
95% CI: [-2.78, -1.31]
Secondary
Mean Ocular Symptom Score and Mean Nasal Ocular Symptom Score
Ocular symptoms (itchy and watery eye) were recorded by the patient everyday in their e-Diary, on a scale of 0 (none) to 4 (intense/severe). Ocular symptom score (0-8 point) consisted of score for severity of itchy eye (0-4 point) and watery eye (0-4 point). Nasal ocular symptom score consisted of nasal symptom score and ocular symptom score. Nasal ocular symptom score is the sum of nasal symptom score (0-12) and ocular symptom score (0-8) 0 presents no nasal ocular symptom and 20 presents worse outcome.
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Mean Ocular Symptom Score and Mean Nasal Ocular Symptom Score | Mean ocular symptom score | 2.45 Score | Standard Error 0.115 |
| Omalizumab | Mean Ocular Symptom Score and Mean Nasal Ocular Symptom Score | Mean nasal ocular symptom score | 6.11 Score | Standard Error 0.24 |
| Placebo | Mean Ocular Symptom Score and Mean Nasal Ocular Symptom Score | Mean ocular symptom score | 3.32 Score | Standard Error 0.11 |
| Placebo | Mean Ocular Symptom Score and Mean Nasal Ocular Symptom Score | Mean nasal ocular symptom score | 8.01 Score | Standard Error 0.228 |
95% CI: [-2.55, -1.24]
95% CI: [-1.18, -0.55]
Secondary
Mean Score for Impairment of Daily Activities
Impairment of daily activities were evaluated on a scale of 0 (none) to 4 (intense/severe).
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Mean Score for Impairment of Daily Activities | 1.09 score | Standard Error 0.052 |
| Placebo | Mean Score for Impairment of Daily Activities | 1.43 score | Standard Error 0.05 |
95% CI: [-0.48, -0.2]
Secondary
Mean Score for Severity of Itchy and Watery Eye
Symptoms of itchy and watery eye were evaluated on a scale of 0 (none) to 4 (intense/severe).
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Mean Score for Severity of Itchy and Watery Eye | Mean itchy eye score | 1.47 score | Standard Error 0.061 |
| Omalizumab | Mean Score for Severity of Itchy and Watery Eye | Mean watery eye score | 0.98 score | Standard Error 0.063 |
| Placebo | Mean Score for Severity of Itchy and Watery Eye | Mean itchy eye score | 1.94 score | Standard Error 0.058 |
| Placebo | Mean Score for Severity of Itchy and Watery Eye | Mean watery eye score | 1.38 score | Standard Error 0.06 |
95% CI: [-0.63, -0.3]
95% CI: [-0.57, -0.23]
Secondary
Mean Score for Severity of Sneezing, Rhinorrhea and Nasal Congestion
Symptoms of sneezing, rhinorrhea and nasal congestion were evaluated on a scale of 0 (none) to 4 (intense/severe).
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Mean Score for Severity of Sneezing, Rhinorrhea and Nasal Congestion | Mean sneezing score | 1.15 score | Standard Error 0.053 |
| Omalizumab | Mean Score for Severity of Sneezing, Rhinorrhea and Nasal Congestion | Mean rhinorrhea score | 1.46 score | Standard Error 0.063 |
| Omalizumab | Mean Score for Severity of Sneezing, Rhinorrhea and Nasal Congestion | Mean nasal congestion score | 1.05 score | Standard Error 0.058 |
| Placebo | Mean Score for Severity of Sneezing, Rhinorrhea and Nasal Congestion | Mean rhinorrhea score | 1.79 score | Standard Error 0.06 |
| Placebo | Mean Score for Severity of Sneezing, Rhinorrhea and Nasal Congestion | Mean sneezing score | 1.56 score | Standard Error 0.05 |
| Placebo | Mean Score for Severity of Sneezing, Rhinorrhea and Nasal Congestion | Mean nasal congestion score | 1.34 score | Standard Error 0.056 |
95% CI: [-0.54, -0.26]
95% CI: [-0.51, -0.16]
95% CI: [-0.45, -0.13]
Secondary
Number of Participants With Anti-omalizumab Antibodes
Number of participants with antibodies against the Fab and Fc region of omalizumab in serum.
Time frame: Prior to first dosing (Day 1), At follow-up investigation which were conducted 20/22 weeks after 12 week-treatment epoch
Population: Safety set (SAF): The SAF consisted of all patients who received at least 1 dose of study drug. Patients in the SAF were analyzed according to treatment actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Number of Participants With Anti-omalizumab Antibodes | Anti-Fab-(pre-dose) | 0 participants |
| Omalizumab | Number of Participants With Anti-omalizumab Antibodes | Anti-Fab (post dose) | 0 participants |
| Omalizumab | Number of Participants With Anti-omalizumab Antibodes | Anti-Fc-(pre-dose) | 1 participants |
| Omalizumab | Number of Participants With Anti-omalizumab Antibodes | Anti-Fc-(post-dose) | 0 participants |
| Placebo | Number of Participants With Anti-omalizumab Antibodes | Anti-Fc-(post-dose) | 2 participants |
| Placebo | Number of Participants With Anti-omalizumab Antibodes | Anti-Fab-(pre-dose) | 0 participants |
| Placebo | Number of Participants With Anti-omalizumab Antibodes | Anti-Fc-(pre-dose) | 2 participants |
| Placebo | Number of Participants With Anti-omalizumab Antibodes | Anti-Fab (post dose) | 0 participants |
Secondary
Number of Rescue Medication Used
Amount number of rescue medication used (a total number of times used).
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Omalizumab | Number of Rescue Medication Used | Number of rescue nasal medication used | 1.0 Number of times used |
| Omalizumab | Number of Rescue Medication Used | Number of ocular rescue medication used | 18.5 Number of times used |
| Placebo | Number of Rescue Medication Used | Number of rescue nasal medication used | 6.0 Number of times used |
| Placebo | Number of Rescue Medication Used | Number of ocular rescue medication used | 28.5 Number of times used |
p-value: 0.00695% CI: [-4.5, 0]van Elteren test
p-value: 0.01295% CI: [-12, -1]van Elteren test
Secondary
Number of Symptom Free Days
Nasal symptom free days (days with all nasal symptoms are not more than mild in severity) during the severe symptom period. Ocular symptom free days (days with all ocular symptoms are not more than mild in severity) during the severe symptom period.
Time frame: Severe symptom period (from 23Feb2018 to 24March2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Omalizumab | Number of Symptom Free Days | Nasal symptom free days | 15 days |
| Omalizumab | Number of Symptom Free Days | Ocular symptom free days | 12 days |
| Placebo | Number of Symptom Free Days | Nasal symptom free days | 10 days |
| Placebo | Number of Symptom Free Days | Ocular symptom free days | 6 days |
p-value: 0.00595% CI: [1, 5]van Elteren test
p-value: <0.00195% CI: [2, 6.5]van Elteren test
Secondary
Rescue Medication Free Days
Number of days with no rescue medication (tramazoline hydrochloride, levocabastine hydrochloride). Nasal ocular rescue medication free days were defined as the days with no use of tramazoline hydrochloride (nasal rescue medication) and levocabastine hydrochloride (ocular rescue medication).
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Omalizumab | Rescue Medication Free Days | Nasal rescue medication free days | 27.0 days |
| Omalizumab | Rescue Medication Free Days | Ocular rescue medication free days | 16.0 days |
| Omalizumab | Rescue Medication Free Days | Nasal ocular rescue medication free days | 12.5 days |
| Placebo | Rescue Medication Free Days | Nasal rescue medication free days | 23.5 days |
| Placebo | Rescue Medication Free Days | Ocular rescue medication free days | 11.0 days |
| Placebo | Rescue Medication Free Days | Nasal ocular rescue medication free days | 9.0 days |
p-value: 0.01195% CI: [0, 3.5]van Elteren test
p-value: 0.07495% CI: [0, 4.8]van Elteren test
p-value: 0.09895% CI: [0, 4]van Elteren test
Secondary
Rescue Medication Score
Rescue medication scores were given for tramazoline hydrochloride (nasal, 1 point) and levocabastine hydrochloride (ocular, 1 point). Rescue medication score for nasal is medication score for Tramazoline hydrochloride, Rescue medication score for ocular is medication score for Levocabastine hydrochloride and Rescue medication score for nasal and ocular is the sum of medication score for Tramazoline hydrochloride and Levocabastine hydrochlorid
Time frame: Severe symptom period (from 23Feb2018 to 24Mar2018)
Population: Full analysis set (FAS): The FAS consisted of all patients in the RAN who received at least 1 dose of study drug. Among patients in the FAS, those who had nasal symptom scores for at least 50% of days during the severe symptom period were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Rescue Medication Score | Nasal rescue medication score | 0.20 score | Standard Error 0.024 |
| Omalizumab | Rescue Medication Score | Ocular rescue medication score | 0.46 score | Standard Error 0.029 |
| Omalizumab | Rescue Medication Score | Nasal ocular rescue medication score | 0.66 score | Standard Error 0.045 |
| Placebo | Rescue Medication Score | Nasal rescue medication score | 0.28 score | Standard Error 0.023 |
| Placebo | Rescue Medication Score | Ocular rescue medication score | 0.54 score | Standard Error 0.027 |
| Placebo | Rescue Medication Score | Nasal ocular rescue medication score | 0.82 score | Standard Error 0.043 |
95% CI: [-0.14, -0.01]
95% CI: [-0.16, 0]
95% CI: [-0.28, -0.04]
Secondary
Serum Trough Omalizumab Concentration
Blood samples were collected Prior to first dosing (Day 1), at Day 29, Day 57, Day 85 and follow-up investigation which were conducted 20/22 weeks after 12 week-treatment epoch
Time frame: Prior to first dosing (Day 1), at Day 29, Day 57, Day 85 and 24 weeks after last dose
Population: Pharmacokinetic set (PK set): The PK set consisted of all randomized patients who received at least 1 dose of study drug and had at least 1 evaluable PK measurement. Patients in the PK set were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Serum Trough Omalizumab Concentration | Day 1 (pre-dose) | 0 μg/mL | Standard Deviation 0 |
| Omalizumab | Serum Trough Omalizumab Concentration | Day 29 | 42.6 μg/mL | Standard Deviation 34.8 |
| Omalizumab | Serum Trough Omalizumab Concentration | Day 57 | 54.1 μg/mL | Standard Deviation 42.3 |
| Omalizumab | Serum Trough Omalizumab Concentration | Day 85 | 66.3 μg/mL | Standard Deviation 49 |
| Omalizumab | Serum Trough Omalizumab Concentration | Day 225/239 | 0.928 μg/mL | Standard Deviation 1.11 |