Study of Efficacy and Safety of Omalizumab in Severe Japanese Cedar Pollinosis Adult and Adolescent Patients

Phase 3

Completed

Conditions: Seasonal Allergic Rhinitis

Interventions: Drug: Omalizumab
Drug: Placebo

Registration Number: NCT03369704

Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 337

Inclusion Criteria

Not provided

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Omalizumab	Omalizumab	Eligible patients randomized to this arm received omalizumab subcutaneously for 12 weeks
Placebo	Placebo	Eligible patients randomized to this arm received placebo subcutaneously for 12 weeks

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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).
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.
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
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).
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
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 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.
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
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.