A Dose-finding Study of ASP4070

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 -

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

Study Overview

• Status: Completed
• Conditions: Rhinitis, Allergic, Seasonal
• Intervention / Treatment: Drug: ASP4070; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Shinjuku, Tokyo, Japan
      • Site JP00001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Collaborators: Immunomic Therapeutics, Inc.

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2017
• Primary Completion (Actual): January 26, 2018
• Study Completion (Actual): October 27, 2018

Study Registration Dates

• First Submitted: April 2, 2017
• First Submitted That Met QC Criteria: April 2, 2017
• First Posted (Actual): April 5, 2017

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 16, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: ASP4070; Cedar pollinosis; DNA plasmid vaccine
• 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
• Other Study ID Numbers: 4070-CL-0020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes