Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.

BACKGROUND: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. METHODS: PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete. FINDINGS: Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, -8·0 (95% CI -10·6 to -5·4; PEARL-1), -10·0 (-12·6 to -7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (-1·2 to 2·5; PEARL-1), 0·4 (-1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo -8·0 (-10·5 to -5·4; PEARL-1), -11·1 (-13·7 to -8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (-1·1 to 2·5; PEARL-1), -0·7 (-2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab. INTERPRETATION: In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies. FUNDING: Novartis Pharma.

Inhibition of KIT for chronic urticaria: a status update on drugs in early clinical development.

INTRODUCTION: Chronic urticaria (CU), including chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), is a prevalent, enduring, mast-cell driven condition that presents challenges in its management. There is a clear need for additional approved treatment options beyond H1 receptor antagonists and the anti-IgE monoclonal antibody (mAb), omalizumab. One of the latest therapeutic strategies targets KIT, which is considered the primary master regulator for mast cell-related disorders. AREAS COVERED: This review provides a status update on KIT inhibiting drugs in early clinical development for CU. EXPERT OPINION: Whereas multi-targeted tyrosine kinase KIT inhibitors carry the risk of off-target toxicities, initial data from anti-KIT mAbs indicate significant potential in CSU and CIndU. The prolonged depletion of mast cells over several weeks by barzolvolimab could effectively control urticarial symptoms. Regarding safety, based on theoretical considerations and the available preliminary results, it is already evident that there may be more side effects compared to omalizumab. However, long-term safety data beyond 12 weeks are still lacking. The outcome of ongoing or planned clinical trials with several anti-KIT mAbs will need to demonstrate benefits compared to anti-IgE in CU or whether one approach is better suited for specific urticaria endotypes.

Norisoboldine exerts antiallergic effects on IgE/ovalbumin-induced allergic asthma and attenuates FcεRI-mediated mast cell activation.

Allergic asthma is an inflammatory lung disorder, and mast cells play crucial roles in the development of this allergic disease. Norisoboldine (NOR), the major isoquinoline alkaloid present in Radix Linderae, has received considerable attention because it has anti-inflammatory effects. Herein, the aim of this study was to explore the antiallergic effects of NOR on allergic asthma in mice and mast cell activation. In a murine model of ovalbumin (OVA)-induced allergic asthma, oral administration at 5 mg/kg body weight (BW) of NOR produced strong reductions in serum OVA-specific immunoglobulin E (IgE) levels, airway hyperresponsiveness, and bronchoalveolar lavage fluid (BALF) eosinophilia, while an increase in CD4+Foxp3+ T cells of the spleen was detected. Histological studies demonstrated that NOR treatment significantly ameliorated the progression of airway inflammation including the recruitment of inflammatory cells and mucus production by decreasing levels of histamine, prostaglandin D2 (PGD2), interleukin (IL)-4, IL-5, IL-6, and IL-13 in BALF. Furthermore, our results revealed that NOR (3 âˆ¼ 30 µM) dose-dependently reduced expression of the high-affinity receptor for IgE (FcεRI) and the production of PGD2 and inflammatory cytokines (IL-4, IL-6, IL-13, and TNF-α), and also decreased degranulation of bone marrow-derived mast cells (BMMCs) activated by IgE/OVA. In addition, a similar suppressive effect on BMMC activation was observed by inhibition of the FcεRI-mediated c-Jun N-terminal kinase (JNK) signaling pathway using SP600125, a selective JNK inhibitor. Collectively, these results suggest that NOR may have therapeutic potential for allergic asthma at least in part through regulating the degranulation and the release of mediators by mast cells.

Long-Term Omalizumab in Elderly Patients with Chronic Urticaria: Is It a Safe Therapy?

BACKGROUND: Biologics have revolutionized the treatment of many diseases. In this regard, omalizumab (OMA), an anti-IgE monoclonal antibody, is the recommended therapeutic option for patients with chronic spontaneous urticaria (CSU) refractory to second-generation H1-antihistamines. Several studies confirm the efficacy and safety of the drug. However, the literature focusing on the elderly population is scarce, as this age group is often excluded from clinical trials. Therefore, the pharmacological treatment of CSU in elderly patients is a challenge that is increased by their comorbidities and consequent polypharmacy. OBJECTIVES: We describe the real-life safety profile of OMA in elderly patients (≥70 years) with CSU and chronic inducible urticaria (CIndU). We aimed to provide data for daily clinical practice in this vulnerable patient group. METHOD: A retrospective review was performed of the records of patients with CSU/CIndU from May 2003 to December 2019 in the Hospital Universitario La Paz. We describe qualitative and quantitative data according to measures of central tendency. Comparisons between qualitative and quantitative data were performed with the Mann-Whitney U test and the Fisher's test for qualitative variables. A p value <0.05 was considered statistically significant. RESULTS AND CONCLUSIONS: Eighty-nine patients were included, divided into two groups (<70 vs. ≥70 years). The overall rate of adverse events (AEs) was 48%, mainly mild. No association between age and AE was found (p = 0.789). No serious AE such as anaphylaxis was detected. CSU predominated in both groups. CIndU was less prevalent in the elderly (p = 0.017). There was no association between age and the other variables. Although the frequency of neoplasms was slightly higher in the elderly with OMA, we found no difference compared to the incidence of neoplasms in the general population. Therefore, our data suggest that OMA may be a safe treatment in elderly people with CSU/CIndU for prolonged periods of treatment, although further studies with larger samples are needed to corroborate our observations.

Efficacy of Once-Daily Ophthalmic Bilastine for the Treatment of Allergic Conjunctivitis: A Dose-Finding Study.

BACKGROUND AND OBJECTIVE: Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis. METHODS: Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated. RESULTS: A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed. CONCLUSION: All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated.

Quail egg homogenate with zinc as adjunctive therapy in seasonal allergic rhinitis: a randomised, controlled trial.

OBJECTIVE: Because most available treatments for managing seasonal allergic rhinitis show some side effects without reducing recurrence, natural anti-allergic products could represent an interesting treatment addition. This study aimed to analyse the efficacy and tolerance of quail egg as adjunctive therapy in seasonal allergic rhinitis. METHOD: In a Consolidated Standards of Reporting Trials compliant framework, patients with seasonal allergic rhinitis were prospectively randomised to receive mometasone nasal spray for four weeks or the same topical corticosteroid therapy plus commercially available oral quail egg and zinc tablets. RESULTS: Forty patients were enrolled. The mometasone + quail egg and zinc tablets group showed a greater reduction in nasal itching, sneezing and total nasal symptom scores than the mometasone nasal spray only group. A higher proportion of participants in the mometasone + quail egg and zinc tablets group had good rhinitis control than in the mometasone nasal spray only group, with no need for rescue medications. CONCLUSION: Despite the need for a further larger study, quail egg preliminarily appears to be an effective adjunct to topical steroid therapy in seasonal allergic rhinitis.

The add-on effect of an intranasal antihistamine with an intranasal corticosteroid in Japanese cedar pollinosis.

OBJECTIVE: Combination intranasal drugs with a corticosteroid and antihistamine are available in several countries with better effect than treatments with single agents. However, it remains unclear whether this effect is also seen in Japanese cedar pollinosis (JCP), the most prevalent seasonal allergic rhinitis in Japan. We investigated the effect of an add-on intranasal antihistamine with an intranasal corticosteroid in JCP during the pollen dispersal period. (UMIN000025508) METHODS: We performed a double-blinded, randomized, placebo-controlled trial from March 1 to 14, 2017. Patients (n = 20 per group) received either a mometasone furoate nasal spray (MFNS) plus a levocabastine nasal spray (levocabastine group) or MFNS plus a placebo nasal spray (placebo group). The primary endpoint was the difference in the total nasal symptom score (TNSS) after treatment between the two groups. Differences in the total ocular symptom score, total symptom score, total medication score, total symptom-medication score, and five individual symptoms as well as safety were the secondary endpoints. RESULTS: The change in the TNSS from baseline was significantly greater in the levocabastine group than in the placebo group. A significant reduction in the TNSS was observed more than 6 days earlier in the levocabastine group than in the placebo group. Such add-on effects were also seen in the secondary endpoints. Both treatments were well-tolerated. CONCLUSION: The intranasal antihistamine provided better control of not only nasal symptoms, but also of ocular symptoms, and decreased the need for rescue medications when added to intranasal corticosteroid treatment in JCP patients.

Real-world safety and effectiveness of omalizumab in Japanese patients with chronic spontaneous urticaria: A post-marketing surveillance study.

BACKGROUND: The safety and efficacy of omalizumab in chronic spontaneous urticaria (CSU) patients has been established, but real-world long-term data remain scarce, especially in Japan. METHODS: 52-week, open-label, single-arm, observational study evaluated the safety and effectiveness of first-time omalizumab in Japanese CSU patients responding inadequately to conventional therapies. RESULTS: Overall, 235 of 280 patients completed the study. Most patients were aged ≥ 18 and < 65 years; adolescents (≥ 12 and ≤ 18 years) accounted for 9.6% of the total population. The mean ± standard deviation (SD) duration of CSU at baseline was 1.6 ± 3.1 years; 46.1% of patients had had CSU for < 6 months. At baseline, the mean ± SD of Urticaria Control Test (UCT) score, Weekly Urticaria Activity Score (UAS7), and Dermatology Life Quality Index (DLQI) were 5.1 ± 3.2, 25.2 ± 11.9, and 8.4 ± 5.9, respectively. The mean ± SD duration of the observation period was 330.3 ± 86.2 days. Relapse was reported in 65 patients, 51, 9, and 5 of whom required retreatment with omalizumab 1, 2, and ≥ 3 times, respectively. The incidence of adverse events (AEs), serious AEs, and adverse drug reactions (ADRs) was reported in 11.8%, 1.4%, and 3.9% of patients, respectively. The most common AEs were urticaria (1.8%) and eczema (1.1%). No adolescents experienced ADRs. A cumulative of 92.8% of patients responded in the Physician's Global Impression of Change, with 81.3%, 75.0%, and 95.1% of patients achieving UCT ≥ 12, UAS7 ≤ 6, and DLQI ≤ 5 up to Week 52, respectively. CONCLUSIONS: This study supports the safety and effectiveness of omalizumab in CSU patients who responded inadequately to conventional therapies in real-world clinical practice in Japan.

Osteonecrosis múltiple inducida por glucocorticoides / Multiple osteonecrosis induced bye glucocorticoids / Osteonecrose múltipla induzida por glicocorticóides

La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.

Multiple osteonecrosis is a rare entity that is defined by the involvement of at least three different regions. A multidisciplinary approach to patients who suffer from it is essential for both diagnosis and timely treatment. We present the clinical case of a young patient who presented multiple osteonecrosis with involvement of both hips, shoulders, knees, right elbow, and neck of the left foot. The main risk factor present in our case is the consumption of glucocorticoids.

A osteonecrose múltipla é uma entidade rara que se define pelo envolvimento de pelo menos três regiões diferentes. Uma abordagem multidisciplinar aos pacientes que sofrem com isso é essencial para o diagnóstico e tratamento oportuno. Apresentamos o caso clínico de um paciente jovem que apresenta osteonecrose múltipla envolvendo quadris, ombros, joelhos, cotovelo direito e pescoço do pé esquerdo. O principal fator de risco presente no nosso caso é o consumo de glicocorticóides.

Predictive factors of recurrence after omalizumab cessation in the elderly with urticaria: A real-life study.

Background: There are no well-defined data that help predict the recurrence risk of urticaria after omalizumab cessation in elderly patients with chronic spontaneous urticaria (CSU). Objective: We aimed to evaluate the effectiveness and safety of omalizumab and to determine the possible predictive factors for recurrence after omalizumab cessation in the elderly with CSU. Methods: A total of 193 patients with CSU treated with omalizumab were included and divided into two groups according to age: group 1, ages 18-64 years (n = 127), and group 2, ages ≥ 65 years (n = 66). Demographics, clinical features, immunoglobulin G (IgG) anti-thyroid peroxidase antibody (anti-TPO), serum total IgE were analyzed. The IgG anti-TPO/total IgE ratio was calculated. Pretreatment 7-day urticaria activity scores, medication scores, and urticaria control test results were compared with those after treatment periods. Adverse effects were also evaluated. Results: The most common adverse effect of omalizumab treatment was injection-site reactions (4.7%) in both groups. Omalizumab was ceased after 24 weeks in 40.9% and in 73.1% in group 1 and group 2, respectively (p < 0.001). CSU recurred after omalizumab discontinuation in 9 and 15 patients in group 1 and in group 2, respectively (p < 0.001). The median baseline IgG anti-TPO was higher in patients with recurrent CSU in group 2 than in those in group 1 (p = 0.002). In group 2, the cutoff values of IgG anti-TPO and the IgG anti-TPO/total IgE ratio were 54.83 IU/mL and 0.45 for recurrence, respectively. Conclusion: Omalizumab is effective and safe in elderly patients with CSU. The serum baseline IgG anti-TPO level and the IgG anti-TPO/total IgE ratio could serve as predictors of recurrence in CSU after omalizumab cessation in elderly patients.

Comparison between chronic spontaneous urticaria and chronic induced urticaria on the efficacy of omalizumab treatment: A systematic review and meta-analysis.

This meta-analysis aimed to assess the efficacy of omalizumab in the treatment of refractory-to-antihistamines chronic induced urticaria (CIndU) in comparison with that of refractory-to-antihistamines chronic spontaneous urticaria (CSU). We retrieved interventional studies and observational studies on omalizumab efficacy to CIndU patients and efficacy comparison between CSU and CIndU both refractory to H1-antihistamines in electronic databases (accessed till May 2022). The odd ratio (OR) and 95% confidence interval (CI) was calculated with a random-effect model in this meta-analysis. The majority of patients with different CIndU subtypes gained complete or partial response and good safety after omalizumab treatment. A total of five studies with 355 CSU patients and 103 CIndU patients were included for the meta-analysis. There was no significant difference in the efficacy of omalizumab in the treatment of CSU and CIndU (OR -0.83, 95% CI [0.84, 2.21], P > 0.05). Based on the validity of omalizumab in the treatment of various CIndU subtypes and non-differential efficacy between CSU and CIndU, it is reasonable to list omalizumab as a third-line treatment of refractory CIndU.

Clinical and laboratory parameters associated with treatment response to third-line therapies in chronic refractory urticaria: A real world study from northern India.

Current guidelines recommend omalizumab and cyclosporine for management of chronic spontaneous urticaria (CSU) refractory to anti-histamines. Identification of clinico-epidemiological characteristics predictive of treatment response with both modalities which will aid therapy selection. Clinical records of CSU patients receiving omalizumab and cyclosporine from May 1, 2016 to December 31, 2020 were reviewed retrospectively. Patients with a minimum follow-up duration of 4 months were included in the analysis. Treatment response was defined as >90% recorded reduction in Urticaria Activity Score-7 (UAS7) as compared to baseline 4 months after treatment initiation. Records of 1364 CSU patients were reviewed. A total of 56 patients who received omalizumab and 132 patients who received cyclosporine fulfilled the inclusion criteria. Treatment response was observed in 46 out of 56 (82.1%) patients in the omalizumab cohort and 106 out of 132 (80.3%) patients in the cyclosporine cohort (P = 0.76). Factors significantly associated with response to omalizumab included high baseline serum IgE levels (P = 0.028), lesser disease duration (P = 0.001), and absence of prior immunosuppressant use (P = 0.024). Factors predictive of cyclosporine response included high baseline UAS7 (P = 0.048), low baseline IgE levels (P = 0.047), and normal baseline D-dimer levels (P = 0.027). Concomitant inducible urticaria, atopy, and angioedema were associated with non-response in both groups (P ≤ 0.05). Incidence of adverse events was slightly higher in cyclosporine group (28.7%) as compared to omalizumab group (19.5%, P = 0.19). This study highlights several clinical parameters and laboratory markers that may be utilized to predict treatment response and aid in prognostication of patients with CSU.

Edible algae (Ecklonia cava) bioprocessed with mycelia of shiitake (Lentinula edodes) mushrooms in liquid culture and its isolated fractions protect mice against allergic asthma.

BACKGROUND: Ecklonia cava is an edible marine brown alga harvested from the ocean that is widely consumed in Asian countries as a health-promoting medicinal food The objective of the present study is to evaluate the anti-asthma mechanism of a new functional food produced by bioprocessing edible algae Ecklonia cava and shiitake Lentinula edodes mushroom mycelia and isolated fractions. METHODS: We used as series of methods, including high performance liquid chromatography, gas chromatography, cell assays, and an in vivo mouse assay to evaluate the asthma-inhibitory effect of Ecklonia cava bioprocessed (fermented) with Lentinula edodes shiitake mushroom mycelium and its isolated fractions in mast cells and in orally fed mice. RESULTS: The treatments inhibited the degranulation of RBL-2H3 cells and immunoglobulin E (IgE) production, suggesting anti-asthma effects in vitro. The in vitro anti-asthma effects in cells were confirmed in mice following the induction of asthma by alumina and chicken egg ovalbumin (OVA). Oral administration of the bioprocessed Ecklonia cava and purified fractions suppressed the induction of asthma and was accompanied by the inhibition of inflammation- and immune-related substances, including eotaxin; thymic stromal lymphopoietin (TSLP); OVA-specific IgE; leukotriene C4 (LTC4); prostaglandin D2 (PGD2); and vascular cell adhesion molecule-1 (VCAM-1) in bronchoalveolar lavage fluid (BALF) and other fluids and organs. Th2 cytokines were reduced and Th1 cytokines were restored in serum, suggesting the asthma-induced inhibitory effect is regulated by the balance of the Th1/Th2 immune response. Serum levels of IL-10, a regulatory T cell (Treg) cytokine, were increased, further favoring reduced inflammation. Histology of lung tissues revealed that the treatment also reversed the thickening of the airway wall and the contraction and infiltration of bronchial and blood vessels and perialveolar inflammatory cells. The bioprocessed Ecklonia cava/mushroom mycelia new functional food showed the highest inhibition as compared with commercial algae and the fractions isolated from the bioprocessed product. CONCLUSIONS: The in vitro cell and in vivo mouse assays demonstrate the potential value of the new bioprocessed formulation as an anti-inflammatory and anti-allergic combination of natural compounds against allergic asthma and might also ameliorate allergic manifestations of foods, drugs, and viral infections.

Urticaria relapse after mRNA COVID-19 vaccines in patients affected by chronic spontaneous urticaria and treated with antihistamines plus omalizumab: A single-center experience.

Urticaria is a disease characterized by wheals and/or angioedema. Chronic spontaneous urticaria (CSU) occurs for longer than 6 weeks and appears independently of any identifiable exogenous stimulus. During the vaccination campaign for Coronavirus disease 2019 (COVID-19) pandemic, several cutaneous adverse events have been described, among which urticaria lasting less than 6 weeks (acute urticaria, AU). AU due to vaccines can be IgE or non-IgE mediated; the former typically develop within 4 h of drug exposure, the latter occurs later and the mechanism is unclear. In this retrospective study we analyzed the frequency and clinical characteristics of urticaria occurring after COVID-19 vaccine (post-vaccination urticaria relapse) in adult CSU patients treated with antihistamine and omalizumab, and in clinical remission.

Vasicine alleviates 2,4-dinitrochlorobenzene-induced atopic dermatitis and passive cutaneous anaphylaxis in BALB/c mice.

Atopic dermatitis (AD), a type of skin inflammation, is associated with immune response mediated by T-helper 2 (Th2) cells, and mast cells. Vasicine is an alkaloid isolated from Adhatoda vasica, a popular Ayurvedic herbal medicine used for treating inflammatory conditions. In the present study, the anti-AD effects of vasicine were evaluated on 2,4-dinitrochlorobenzene-induced AD-like skin lesions in BALB/c mice. The potential anti-allergic effects of vasicine were also assessed using the passive cutaneous anaphylaxis (PCA) test. The results showed that the oral administration of vasicine improved the severity of AD-like lesional skin by decreasing histopathological changes and restoring epidermal thickness. Vasicine also inhibited the infiltration of mast cells in the skin and reduced the levels of pro-Th2 and Th2 cytokines as well as immunoglobulin E in the serum. Finally, vasicine inhibited the expression of pro-Th2 and Th2 cytokines in skin tissues, indicating the therapeutic potential of vasicine for AD.

Efficacy and safety of GSP301 nasal spray in children aged 6 to 11 years with seasonal allergic rhinitis.

BACKGROUND: GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of GSP301 in pediatric patients (aged ≥6 to <12 years) with seasonal allergic rhinitis (SAR). METHODS: This double-blind, randomized, parallel-group study randomized 446 eligible patients 1:1 (GSP301 [olopatadine hydrochloride 665 µg and mometasone furoate 25 µg] or placebo) as 1 spray/each nostril twice daily for 14 days. The primary end point was change from baseline in average morning and evening subject-reported 12-hour reflective Total Nasal Symptom Score (rTNSS) over a 14-day treatment period analyzed using mixed-effect model repeated measures. Additional assessments included instantaneous Total Nasal Symptom Score, Pediatric Rhinoconjunctivitis Quality of Life Questionnaire, reflective Total Ocular Symptoms Score, instantaneous Total Ocular Symptoms Score, individual symptoms, Physician-assessed Nasal Symptom Score, and adverse events. RESULTS: GSP301 showed clinically meaningful and statistically significant improvement in rTNSS vs placebo (-0.6; 95% confidence interval, -0.9 to -0.2; P = .001). Statistically significant improvements favoring GSP301 were shown for all individual rTNSS symptoms, instantaneous Total Nasal Symptom Score, and most of its individual symptoms, Physician-assessed Nasal Symptom Score (P = .01), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (P < .001). For ocular symptoms, numerical improvements favoring GSP301 were observed, with statistical significance achieved only for reflective "tearing/watering eyes" (P = .04). Treatment-emergent adverse events occurred in 12.0% and 10.4% of patients in the GSP301 and placebo groups, respectively. One subject (0.5%) (placebo group) experienced a serious adverse event (suspected viral meningitis) that was not related to the study treatment and was resolved. CONCLUSION: GSP301 was well tolerated and efficacious for treating SAR symptoms in pediatric patients and showed a favorable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03463031.