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MP29-02 in the Treatment of Nasal Symptoms of Seasonal Allergic Rhinitis
Abstracts AB199
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Intranasal Toll-like Receptor 8 Agonist (VTX-1463) Significantly Improves Symptoms of Allergic Rhinitis in a Randomized, Placebo-Controlled Trial F. Horak1, P. Zieglmayer1, R. Zieglmayer1, P. Lemell1, M. Newkirk2, K. Manjarrez2, T. D. Randall2, R. Hershberg2; 1Vienna Challenge Chamber, Vienna, AUSTRIA, 2VentiRx Pharmaceuticals, Seattle, WA. RATIONALE: Toll-like receptors (TLRs) have been shown to modulate allergic immune responses. The safety and efficacy of VTX-1463_a novel, small-molecule, TLR8 agonist given once weekly intranasally_was assessed in allergic rhinitis (AR) subjects exposed to allergen in the Vienna Challenge Chamber (VCC). METHODS: This randomized, double-blind, placebo-controlled study was conducted in-season, and enrolled 80 adults with confirmed atopy to grass pollen. Two dosing regimens were compared to placebo: ascending dose (GrpA; 25mcg, 50mcg, 75mcg, 100mcg) and fixed dose (GrpB; 62.5mcg x 4 doses). Subjects were dosed on Days 1, 8, 15 and 22. On Day 24, subjects underwent grass allergen exposure in the VCC, a validated setting for assessing the efficacy of anti-allergic treatment. The primary efficacy endpoints were the average change over 6 hours of allergen exposure in Total Nasal Symptom Score (TNSS; the sum of scores for nasal congestion, itching, sneezing and rhinorrhea) and Active Anterior Rhinomanometry (AAR). Adverse event data were collected for all subjects. RESULTS: Subjects in the overall efficacy population (n576) who were treated with VTX-1463 and underwent allergen challenge had significantly improved TNSS compared to placebo (p50.012). This benefit was observed in both GrpA (p50.008) and GrpB (p50.012). AAR trended towards a benefit in both treatment groups, but was not statistically significant. VTX-1463 was generally well tolerated. CONCLUSIONS: Four doses of VTX-1463 conferred statistically significant improvement in TNSS compared to placebo. This TLR8 agonist may represent a novel, weekly-administered treatment for AR.
764
Onset of Action of MP29-02 in the Treatment of Seasonal Allergic Rhinitis J. A. Bernstein1, U. Munzel2, W. Wheeler3, H. Sacks3; 1University of Cincinnati College of Medicine, Cincinnati, OH, 2MEDA Pharma GmbH & Co, Homburg, GERMANY, 3Meda Pharmaceuticals, Inc., Somerset, NJ. RATIONALE: In that optimal treatment of seasonal allergic rhinitis (SAR) should reduce symptoms as effectively and as quickly as possible, an important objective of this study (MP 4004) was to evaluate the onset of action of MP29-02 (azelastine and fluticasone propionate [FP]) in a single nasal spray delivery device compared to azelastine, FP, and placebo nasal sprays. METHODS: A 2-week, randomized, double-blind, placebo-controlled trial was conducted in patients with SAR. The study compared the MP29-02 formulation with azelastine, FP, and placebo nasal sprays alone. The primary efficacy variable was the change from baseline in the 12-hour reflective total nasal symptom score (TNSS) with four nasal symptoms scored twice daily on a 4-point scale (daily maximum 24). A clinically relevant secondary efficacy variable was onset of action, defined as sustained statistically significant superiority versus placebo in instantaneous TNSS during a 4-hour observation period. Early symptom relief was also supported by a post-hoc responder analysis of time-to-response (50% improvement in TNSS). RESULTS: Onset of action was achieved within 30 minutes for MP29-02 vs placebo. Time-to-response was statistically significantly earlier _0.0497) with more responders observed for MP29-02 (53.5% vs (p< _43.7%) compared to azelastine, FP, or placebo alone. < CONCLUSIONS: MP29-02 may represent an important therapeutic option for patients with SAR because it has a fast onset of action and is more effective than monotherapy with a nasal antihistamine or nasal corticosteroid.
765
MP29-02 in the Treatment of Nasal Symptoms of Seasonal Allergic Rhinitis W. Carr1, S. R. Shah2, W. Wheeler3, H. Sacks3; 1Allergy & Asthma Associates, Mission Viejo, CA, 2PA Allergy & Asthma Consultants, Collegeville, PA, 3Meda Pharmaceuticals, Inc., Somerset, NJ.
RATIONALE: The objective of this study (MP 4004) was to evaluate the efficacy of MP29-02 nasal spray (a novel formulation of azelastine and fluticasone propionate [FP]) compared to azelastine, FP, and placebo nasal sprays. METHODS: This was a 2-week, randomized, double-blind, placebo-controlled trial in patients with seasonal allergic rhinitis (SAR). It compared MP29-02 with azelastine, FP, and placebo nasal sprays alone. All treatments were administered 1 spray per nostril twice daily (AM and PM) in the same delivery device. Total daily dose of azelastine and FP in the single delivery device was 548 mcg and 200 mcg, respectively. The primary efficacy variable was the change from baseline in the 12-hour reflective total nasal symptom score (TNSS), consisting of nasal congestion, sneezing, itchy nose, and runny nose. Symptoms were scored twice daily on a 4-point scale (daily maximum 24). RESULTS: Over the 2 weeks of treatment, the mean TNSS improvement from baseline with MP29-02 (5.54) was statistically significantly superior compared to azelastine (4.54; p5.032), FP (4.55; p5.038), or placebo (3.03; p<.001). Headache (6.1%) and bitter taste (2.1%) were the most commonly reported adverse events with MP29-02. CONCLUSIONS: MP29-02 may represent an important treatment option for patients with SAR. It was more effective than nasal antihistamine or nasal corticosteroid monotherapy and was well tolerated in treating nasal symptoms associated with SAR.
766
Dietary Antioxidant May Affect the Development of Allergic Rhinitis, but Not in Atopy, in Korean School-children J. Seo1, J. Kwon1, B. Kim2, J. Yu1, H. Kim3, S. Lee4, W. Kim5, K. Kim6, S. Kwon7, S. Oh7, Y. Shin8, S. Hong1; 1Childhood Asthma Atopy Center, Department of Pediatrics, Asan Medical Center, Seoul, KOREA, REPUBLIC OF, 2Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan, KOREA, REPUBLIC OF, 3Pediatric Asthma & Allergy Center, Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, KOREA, REPUBLIC OF, 4Department of Pediatrics, Hallym University Sacred Heart Hospital, Anyang, KOREA, REPUBLIC OF, 5Department of Pediatrics, Inje University Seoul Paik Hospital, Seoul, KOREA, REPUBLIC OF, 6Department of Pediatrics, Severance Hospital, Seoul, KOREA, REPUBLIC OF, 7Department of Food and Nutrition, College of Human Ecology, Kyung Hee University, Seoul, KOREA, REPUBLIC OF, 8Department of Psychiatry, Severance Hospital, Seoul, KOREA, REPUBLIC OF. RATIONALE: We investigated the association between antioxidant nutritional status and the development of allergic rhinitis (AR) in Korean school-children aged 6-12 years old. METHODS: A modified International Study of Asthma and Allergies in Childhood (ISSAC) questionnaire and semi-quantitative food frequency questionnaire (FFQ) were conducted in 4,539 children. The amount of each food item was converted into grams and then each nutrient was calculated by using Computer Aided Nutritional Analysis Programs II (CAN PRO II) developed by the Korean Nutrition Society. The vitamin A (including retinol and b-carotene), C, E and zinc were used in the analysis. And skin prick test and blood sampling were done among 1,371 children of one elementary school. RESULTS: The lifetime diagnosis of AR was reported in 33.9% of children and current AR was 21.1%. Vitamin C was negatively associated with an increased risk of current AR symptoms (OR50.886, 95% CI50.806-0.973). Zinc was positively associated with diagnosis and treatment of allergic rhinitis (OR51.101, 95% CI51.006-1.204 and OR51.107, 95% CI51.008-1.216 respectively). There is no association between vitamin A, retinol, b-carotene, vitamin E and AR. Also, the associations between serum IgE or allergen sensitization and dietary antioxidants were not significant. CONCLUSIONS: Higher consumption of vitamin C may protect the development of current symptoms of AR. Higher zinc intake may be the risk factor in diagnosis and treatment of allergic rhinitis. These findings suggest that nutrients including vitamin C and Zinc may affect the development of allergic rhinitis.
MONDAY
763
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Intranasal Toll-like Receptor 8 Agonist (VTX-1463) Significantly Improves Symptoms of Allergic Rhinitis in a Randomized, Placebo-Controlled Trial F. Horak1, P. Zieglmayer1, R. Zieglmayer1, P. Lemell1, M. Newkirk2, K. Manjarrez2, T. D. Randall2, R. Hershberg2; 1Vienna Challenge Chamber, Vienna, AUSTRIA, 2VentiRx Pharmaceuticals, Seattle, WA. RATIONALE: Toll-like receptors (TLRs) have been shown to modulate allergic immune responses. The safety and efficacy of VTX-1463_a novel, small-molecule, TLR8 agonist given once weekly intranasally_was assessed in allergic rhinitis (AR) subjects exposed to allergen in the Vienna Challenge Chamber (VCC). METHODS: This randomized, double-blind, placebo-controlled study was conducted in-season, and enrolled 80 adults with confirmed atopy to grass pollen. Two dosing regimens were compared to placebo: ascending dose (GrpA; 25mcg, 50mcg, 75mcg, 100mcg) and fixed dose (GrpB; 62.5mcg x 4 doses). Subjects were dosed on Days 1, 8, 15 and 22. On Day 24, subjects underwent grass allergen exposure in the VCC, a validated setting for assessing the efficacy of anti-allergic treatment. The primary efficacy endpoints were the average change over 6 hours of allergen exposure in Total Nasal Symptom Score (TNSS; the sum of scores for nasal congestion, itching, sneezing and rhinorrhea) and Active Anterior Rhinomanometry (AAR). Adverse event data were collected for all subjects. RESULTS: Subjects in the overall efficacy population (n576) who were treated with VTX-1463 and underwent allergen challenge had significantly improved TNSS compared to placebo (p50.012). This benefit was observed in both GrpA (p50.008) and GrpB (p50.012). AAR trended towards a benefit in both treatment groups, but was not statistically significant. VTX-1463 was generally well tolerated. CONCLUSIONS: Four doses of VTX-1463 conferred statistically significant improvement in TNSS compared to placebo. This TLR8 agonist may represent a novel, weekly-administered treatment for AR.
764
Onset of Action of MP29-02 in the Treatment of Seasonal Allergic Rhinitis J. A. Bernstein1, U. Munzel2, W. Wheeler3, H. Sacks3; 1University of Cincinnati College of Medicine, Cincinnati, OH, 2MEDA Pharma GmbH & Co, Homburg, GERMANY, 3Meda Pharmaceuticals, Inc., Somerset, NJ. RATIONALE: In that optimal treatment of seasonal allergic rhinitis (SAR) should reduce symptoms as effectively and as quickly as possible, an important objective of this study (MP 4004) was to evaluate the onset of action of MP29-02 (azelastine and fluticasone propionate [FP]) in a single nasal spray delivery device compared to azelastine, FP, and placebo nasal sprays. METHODS: A 2-week, randomized, double-blind, placebo-controlled trial was conducted in patients with SAR. The study compared the MP29-02 formulation with azelastine, FP, and placebo nasal sprays alone. The primary efficacy variable was the change from baseline in the 12-hour reflective total nasal symptom score (TNSS) with four nasal symptoms scored twice daily on a 4-point scale (daily maximum 24). A clinically relevant secondary efficacy variable was onset of action, defined as sustained statistically significant superiority versus placebo in instantaneous TNSS during a 4-hour observation period. Early symptom relief was also supported by a post-hoc responder analysis of time-to-response (50% improvement in TNSS). RESULTS: Onset of action was achieved within 30 minutes for MP29-02 vs placebo. Time-to-response was statistically significantly earlier _0.0497) with more responders observed for MP29-02 (53.5% vs (p< _43.7%) compared to azelastine, FP, or placebo alone. < CONCLUSIONS: MP29-02 may represent an important therapeutic option for patients with SAR because it has a fast onset of action and is more effective than monotherapy with a nasal antihistamine or nasal corticosteroid.
765
MP29-02 in the Treatment of Nasal Symptoms of Seasonal Allergic Rhinitis W. Carr1, S. R. Shah2, W. Wheeler3, H. Sacks3; 1Allergy & Asthma Associates, Mission Viejo, CA, 2PA Allergy & Asthma Consultants, Collegeville, PA, 3Meda Pharmaceuticals, Inc., Somerset, NJ.
RATIONALE: The objective of this study (MP 4004) was to evaluate the efficacy of MP29-02 nasal spray (a novel formulation of azelastine and fluticasone propionate [FP]) compared to azelastine, FP, and placebo nasal sprays. METHODS: This was a 2-week, randomized, double-blind, placebo-controlled trial in patients with seasonal allergic rhinitis (SAR). It compared MP29-02 with azelastine, FP, and placebo nasal sprays alone. All treatments were administered 1 spray per nostril twice daily (AM and PM) in the same delivery device. Total daily dose of azelastine and FP in the single delivery device was 548 mcg and 200 mcg, respectively. The primary efficacy variable was the change from baseline in the 12-hour reflective total nasal symptom score (TNSS), consisting of nasal congestion, sneezing, itchy nose, and runny nose. Symptoms were scored twice daily on a 4-point scale (daily maximum 24). RESULTS: Over the 2 weeks of treatment, the mean TNSS improvement from baseline with MP29-02 (5.54) was statistically significantly superior compared to azelastine (4.54; p5.032), FP (4.55; p5.038), or placebo (3.03; p<.001). Headache (6.1%) and bitter taste (2.1%) were the most commonly reported adverse events with MP29-02. CONCLUSIONS: MP29-02 may represent an important treatment option for patients with SAR. It was more effective than nasal antihistamine or nasal corticosteroid monotherapy and was well tolerated in treating nasal symptoms associated with SAR.
766
Dietary Antioxidant May Affect the Development of Allergic Rhinitis, but Not in Atopy, in Korean School-children J. Seo1, J. Kwon1, B. Kim2, J. Yu1, H. Kim3, S. Lee4, W. Kim5, K. Kim6, S. Kwon7, S. Oh7, Y. Shin8, S. Hong1; 1Childhood Asthma Atopy Center, Department of Pediatrics, Asan Medical Center, Seoul, KOREA, REPUBLIC OF, 2Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan, KOREA, REPUBLIC OF, 3Pediatric Asthma & Allergy Center, Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, KOREA, REPUBLIC OF, 4Department of Pediatrics, Hallym University Sacred Heart Hospital, Anyang, KOREA, REPUBLIC OF, 5Department of Pediatrics, Inje University Seoul Paik Hospital, Seoul, KOREA, REPUBLIC OF, 6Department of Pediatrics, Severance Hospital, Seoul, KOREA, REPUBLIC OF, 7Department of Food and Nutrition, College of Human Ecology, Kyung Hee University, Seoul, KOREA, REPUBLIC OF, 8Department of Psychiatry, Severance Hospital, Seoul, KOREA, REPUBLIC OF. RATIONALE: We investigated the association between antioxidant nutritional status and the development of allergic rhinitis (AR) in Korean school-children aged 6-12 years old. METHODS: A modified International Study of Asthma and Allergies in Childhood (ISSAC) questionnaire and semi-quantitative food frequency questionnaire (FFQ) were conducted in 4,539 children. The amount of each food item was converted into grams and then each nutrient was calculated by using Computer Aided Nutritional Analysis Programs II (CAN PRO II) developed by the Korean Nutrition Society. The vitamin A (including retinol and b-carotene), C, E and zinc were used in the analysis. And skin prick test and blood sampling were done among 1,371 children of one elementary school. RESULTS: The lifetime diagnosis of AR was reported in 33.9% of children and current AR was 21.1%. Vitamin C was negatively associated with an increased risk of current AR symptoms (OR50.886, 95% CI50.806-0.973). Zinc was positively associated with diagnosis and treatment of allergic rhinitis (OR51.101, 95% CI51.006-1.204 and OR51.107, 95% CI51.008-1.216 respectively). There is no association between vitamin A, retinol, b-carotene, vitamin E and AR. Also, the associations between serum IgE or allergen sensitization and dietary antioxidants were not significant. CONCLUSIONS: Higher consumption of vitamin C may protect the development of current symptoms of AR. Higher zinc intake may be the risk factor in diagnosis and treatment of allergic rhinitis. These findings suggest that nutrients including vitamin C and Zinc may affect the development of allergic rhinitis.
MONDAY
763