A Dose-finding Study of ASP4070

Study Overview
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Brief Summary
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The objective of this study was to evaluate the efficacy, safety, and dose-response of ASP4070 vaccinated in patients with cedar pollinosis.

Detailed Description
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Subjects were vaccinated with ASP4070 or placebo at 2 week intervals. Clinical symptoms were evaluated after cedar pollen exposure in a chamber at 4, 8 and 12 weeks after the last vaccination to identify the timing of the onset of therapeutic effect.

Official Title
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Phase 2 Dose-finding Study of ASP4070 - A Randomized, Double-blind, Placebo-controlled, Dose-finding Study in Patients With Cedar Pollinosis Using an Environmental Exposure Chamber -

Conditions
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Rhinitis, Allergic, Seasonal

Intervention / Treatment
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* Drug: ASP4070
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject who has exhibited symptoms of cedar pollinosis, consisting of nasal symptoms (sneezing, nasal discharge or nasal obstruction) and eye symptoms (itchy eyes or watery eyes) during the pollen dispersal seasons in 2016 and 2017 Subject who is positive for the Japanese red cedar (JRC) pollen-specific serum IgE antibody test At screening, subject whose score has worsened compared to baseline over 120 to 180 minutes after cedar pollen exposure in a chamber Exclusion Criteria: Subject who has positive the test result of serum IgE antibody specific to other antigen than JRC pollen at screening Subject who has received specific immunotherapy (including desensitization therapy) for cedar pollinosis in the past Subject who has received specific or non-specific immunotherapy within 5 years prior to screening Subject who has received laser therapy or surgery for the treatment of nasal symptoms within 3 years prior to screening. Subject who has a history of allergic reactions such as anaphylactic shock and exanthema generalized caused by food and/or medical products in the past Subject who has a positive test result for hepatitis B surface (HBs) antigen or anti-hepatitis C virus (HCV) antibody Subject who has nasal disease that may interfere with the evaluation Subject who has autoimmune disease or other serious primary disease Subject who was diagnosed with immunodeficiency in the past Subject who has a complication of seasonal allergic rhinitis (due to allergens other than Japanese cedars or cypress), perennial allergic rhinitis, rhinitis medicamentosa, or non-allergic rhinitis that requires medical treatment Subject who has a complication of cardiovascular disease Subject who has a complication of hepatic disease Subject who has a complication of renal disease Subject who has a complication of respiratory disease Subject has a complication of malignant tumor or has been diagnosed with or has received treatment for malignant tumor within 5 years prior to the first vaccination of the study drug Subject who was diagnosed with schizophrenia, other mental conditions Subject who has a complication that may have an impact on the results of the local or systemic reaction Subject who has received a vaccination of Cry j 2-LAMP vaccine Subject who has participated in a clinical study of ASP4070 and received a vaccination of the study drug.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP4070 4 mg<br>Participants received ASP4070 4 mg 8 times by intradermal vaccination at 14-day intervals. | Drug: ASP4070<br>* Intradermal vaccination at 2-week intervals<br>|
| Experimental: ASP4070 1 mg<br>Participants received ASP4070 1 mg 8 times by intradermal vaccination at 14-day intervals. | Drug: ASP4070<br>* Intradermal vaccination at 2-week intervals<br>|
| Placebo Comparator: Placebo<br>Participants received Placebo 8 times by intradermal vaccination at 14-day intervals. | Drug: Placebo<br>* Intradermal vaccination at 2-week intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Pre-Exposure in Mean Total 3 Nasal Symptom Score (3TNSS) 120 to 180 Minutes After Start of Cedar Pollen Exposure on Day 183 | Participants were assessed for each symptom (sneezing, nasal discharge and nasal congestion) using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but does not interfere with the activities of daily living) Very severe (difficult to tolerate and interferes with the activities of daily living). 3TNSS was a summed score of each symptom, and mean of 3TNSS at 120 to 180 min is the average of 5 timepoints of 3TNSS score, which ranged from 0 to 12. Higher 3TNSS score indicated greater disease activity. | Day 183 at pre-exposure and 120 to 180 minutes after the start of cedar pollen exposure (5 samples 15 minutes apart) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Pre-Exposure in Mean Total 4 Nasal Symptom Score (4TNSS) 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for each symptom (sneezing, nasal discharge, nasal congestion and itchy nose) using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living). 4TNSS was a summed score of each symptom, and mean of 4TNSS at 120 to 180 min is the average of 5 timepoints of 4TNSS score, which ranged from 0 to 16. Higher 4TNSS score indicated greater disease activity. | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Sneezing Score 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for sneezing using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. The mean of score at 120 to 180 minutes was calculated. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living) | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Nasal Discharge Score 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for nasal discharge using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. The mean of score at 120 to 180 minutes was calculated. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living) | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Mean Nasal Congestion Score 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for nasal congestion using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. The mean of score at 120 to 180 minutes was calculated. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living) | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Mean Itchy Nose Score 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for itchy nose using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. The mean of score at 120 to 180 minutes was calculated. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living) | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Mean Total Non-Nasal Symptom Score (TNNSS) 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for each non-nasal symptom (itchy eyes and watery eyes) using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living). TNNSS was a summed score of each symptom, and mean of TNNSS at 120 to 180 min is the average of 5 timepoints of TNNSS score, which ranged from 0 to 8. Higher TNNSS score indicated greater disease activity. | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Mean Itchy Eyes Score 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for itchy eyes using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. The mean of score at 120 to 180 minutes was calculated. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living) | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Mean Watery Eyes Score 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for watery eyes using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. The mean of score at 120 to 180 minutes was calculated. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living) | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Total 5 Symptom Score (5TSS) 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for each 5TSS (sneezing, nasal discharge, nasal congestion, itchy eyes and watery eyes) using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living). 5TSS was a summed score of each symptom, and mean of 5TSS at 120 to 180 min is the average of 5 timepoints of 5TSS score, which ranged from 0 to 20. Higher 5TSS score indicated greater disease activity. | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Change From Pre-Exposure in Mean Total 6 Symptom Score (6TSS) 120 to 180 Minutes After Cedar Pollen Exposure | Participants were assessed for each 6TSS (sneezing, nasal discharge, nasal congestion, itchy nose, itchy eyes and watery eyes) using the following score every 15 minutes from before cedar pollen exposure until 180 minutes after cedar pollen exposure. 0: None (no symptoms) Mild (symptoms present but easily tolerated) Moderate (awareness of symptoms; bothersome, but tolerable) Severe (definite awareness of symptoms; difficult to tolerate, but did not interfere with the activities of daily living) Very severe (difficult to tolerate and interfered with the activities of daily living). 6TSS was a summed score of each symptom, and mean of 6TSS at 120 to 180 min is the average of 5 timepoints of 6TSS score, which ranged from 0 to 24. Higher 6TSS score indicated greater disease activity. | Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183 | 
| Time to Occurrence of Nasal or Eye Symptom From Start of Cedar Pollen Exposure | Time point when the score of nasal or eye symptom worsens by 1 or more as compared to before cedar pollen exposure were assessed. | Days 127, 155 and 183, from the start of cedar pollen exposure for up to 180 minutes | 
| Amount of Nasal Discharge Per 30 Minutes During Cedar Pollen Exposure | Nasal discharge amount was calculated by the difference in the weight of the tissue paper before and after use by participants who were instructed to use pre-allocated tissues for blowing their nose. | Day 127: 0-30 min, 30-60 min, 60-90 min, 90-120 min, 120-150 min, 150-180 min, Day 155: 0-30 min, 30-60 min, 60-90 min, 90-120 min, 120-150 min, 150-180 min, Day 183: 0-30 min, 30-60 min, 60-90 min, 90-120 min, 120-150 min, 150-180 min | 
| Sneezing Count Per 30 Minutes During Cedar Pollen Exposure | Sneezing count per 30 minutes were measured during chamber exposure. | Day 127: 0-30 min, 30-60 min, 60-90 min, 90-120 min, 120-150 min, 150-180 min, Day 155: 0-30 min, 30-60 min, 60-90 min, 90-120 min, 120-150 min, 150-180 min, Day 183: 0-30 min, 30-60 min, 60-90 min, 90-120 min, 120-150 min, 150-180 min | 
| Number of Participants With Adverse Events (AE) During the Primary Study Period | Treatment emergent adverse events (TEAE) was defined as an AE observed after starting administration of the test drug/comparative drug. A drug-related TEAE was a TEAE with either possible or probable relationship to the study drug as assessed by the investigator. Severity of AEs was assessed according to the following 4 levels. Mild: no disruption of normal daily activities, Moderate: affect normal daily activities, Severe: inability to perform daily activities, Life-threatening: necessity for urgent intervention. If the investigator or subinvestigator examined the patient and determined that the following items occurred from the date of study drug vaccination until 14 days after vaccination and a relationship with the study drug could not be negated, then it was evaluated as a local/systemic reaction at the vaccination site. Local reactions: pain, tenderness, erythema/redness and induration/swelling Systemic reactions: nausea/vomiting, diarrhea, headache, fatigue and myalgia | From first dose of study drug up to the end of primary study period (up to 7 days after Day 183) | 
| Number of Participants With Serious Adverse Events (SAE) During the Long-Term Safety Follow-Up Period | If SAEs occurred, then the participant was to contact the study site. With regard to participants who had discontinued the study during the primary study period, if the study drug had been vaccinated even once, then safety information (SAEs) was collected for 1 year after the final vaccination. | Up to 9 months after the end of primary study period (primary study period was up to 7 days after Day 183) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cedar pollinosis, ASP4070, DNA plasmid vaccine