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

A 12 Week, Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Omalizumab in Adult and Adolescent Patients With Inadequately Controlled Severe Japanese Cedar Pollinosis Despite the Current Recommended Therapies

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.

Study Overview

• Status: Completed
• Conditions: Seasonal Allergic Rhinitis
• Intervention / Treatment: Drug: Omalizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 337
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Chiba-city, Chiba, Japan, 262-0015
      • Novartis Investigative Site
    • Ichikawa-city, Chiba, Japan, 272-0143
      • Novartis Investigative Site
    • Kashiwa-city, Chiba, Japan, 2270082
      • Novartis Investigative Site
    • Matsudo-city, Chiba, Japan, 270-0034
      • Novartis Investigative Site
    • Matsudo-city, Chiba, Japan, 2710077
      • Novartis Investigative Site
    • Urayasu city, Chiba, Japan, 279-0012
      • Novartis Investigative Site
  • Kanagawa
    • Kawasaki-city, Kanagawa, Japan, 212-0027
      • Novartis Investigative Site
    • Kawasaki-city, Kanagawa, Japan, 216 0006
      • Novartis Investigative Site
    • Kawasaki-city, Kanagawa, Japan, 216-0002
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan
      • Novartis Investigative Site
  • Saitama
    • Koshigaya-city, Saitama, Japan, 343-0031
      • Novartis Investigative Site
  • Tokyo
    • Arakawa-ku, Tokyo, Japan, 116 0011
      • Novartis Investigative Site
    • Chiyoda-ku, Tokyo, Japan, 101-0063
      • Novartis Investigative Site
    • Chuo ku, Tokyo, Japan, 103 0027
      • Novartis Investigative Site
    • Edogawa-ku, Tokyo, Japan, 132-0014
      • Novartis Investigative Site
    • Katsushika-ku, Tokyo, Japan, 125-0061
      • Novartis Investigative Site
    • Nakano-ku, Tokyo, Japan, 164-0012
      • Novartis Investigative Site
    • Setagaya-ku, Tokyo, Japan, 158-0097
      • Novartis Investigative Site
    • Shinjuku ku, Tokyo, Japan, 160-0008
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-0017
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan
      • Novartis Investigative Site
    • Toshima-Ku, Tokyo, Japan, 170-0005
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omalizumab; Eligible patients randomized to this arm received omalizumab subcutaneously for 12 weeks	Drug: Omalizumab; 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.
Placebo Comparator: Placebo; Eligible patients randomized to this arm received placebo subcutaneously for 12 weeks	Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Severe symptom period (from 23Feb2018 to 24March2018)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Severe symptom period (from 23Feb2018 to 24Mar2018)
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).	Severe symptom period (from 23Feb2018 to 24Mar2018)
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).	Severe symptom period (from 23Feb2018 to 24Mar2018)
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).	Severe symptom period (from 23Feb2018 to 24Mar2018)
Mean Score for Impairment of Daily Activities	Impairment of daily activities were evaluated on a scale of 0 (none) to 4 (intense/severe).	Severe symptom period (from 23Feb2018 to 24Mar2018)
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.	Severe symptom period (from 23Feb2018 to 24March2018)
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.	Severe symptom period (from 23Feb2018 to 24Mar2018)
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	Severe symptom period (from 23Feb2018 to 24Mar2018)
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).	Severe symptom period (from 23Feb2018 to 24Mar2018)
Number of Rescue Medication Used	Amount number of rescue medication used (a total number of times used).	Severe symptom period (from 23Feb2018 to 24Mar2018)
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.	Evaluation Visit, one visit during severe symptom period (23-Feb-2018 to 24-Mar-2018) for each patient
Number of Participants With Anti-omalizumab Antibodes	Number of participants with antibodies against the Fab and Fc region of omalizumab in serum.	Prior to first dosing (Day 1), At follow-up investigation which were conducted 20/22 weeks after 12 week-treatment epoch
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	Prior to first dosing (Day 1), at Day 29, Day 57, Day 85 and 24 weeks after last dose
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	Day 1, at Day 29, Day 57, Day 85 and 24 weeks after last dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): May 11, 2018
• Study Completion (Actual): October 20, 2018

Study Registration Dates

• First Submitted: November 14, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 12, 2017

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: cryptomeria, omalizumab, seasonal allergic rhinitis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: CIGE025F1301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No