A Dose-finding Study of ASP4070

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Patrocinadors

Astellas Pharma Inc

Col·laboradors

Immunomic Therapeutics, Inc.

ASSAIG CLÍNIC: NCT03101267

BioSeek: nct03101267

Paraules clau

Resum

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

Descripció

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.

Dates

Darrera verificació:	04/30/2020
Primer enviat:	04/01/2017
Inscripció estimada enviada:	04/01/2017
Publicat per primera vegada:	04/04/2017
Última actualització enviada:	06/15/2020
Publicació de l'última actualització:	06/29/2020
Data dels primers resultats enviats:	05/09/2020
Data dels primers resultats de control de qualitat enviats:	05/09/2020
Data dels primers resultats publicats:	06/03/2020
:	01/03/2019
:	01/03/2019
:	01/06/2019
Data d'inici de l'estudi real:	04/12/2017
Data estimada de finalització primària:	01/25/2018
Data estimada de finalització de l’estudi:	10/26/2018

Condició o malaltia

Rhinitis, Allergic, Seasonal

Intervenció / tractament

Drug: ASP4070

Drug: Placebo

Fase

Fase 2

Grups de braços

Braç	Intervenció / tractament
Experimental: ASP4070 4 mg Participants received ASP4070 4 mg 8 times by intradermal vaccination at 14-day intervals.
Experimental: ASP4070 1 mg Participants received ASP4070 1 mg 8 times by intradermal vaccination at 14-day intervals.
Placebo Comparator: Placebo Participants received Placebo 8 times by intradermal vaccination at 14-day intervals.	Drug: Placebo Intradermal vaccination at 2-week intervals

Criteris d'elegibilitat

Edats elegibles per estudiar	20 Years Per a 20 Years
Sexes elegibles per estudiar	All
Accepta voluntaris saludables	Sí
Criteris	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.

Resultat

Mesures de resultats primaris

1. 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 [Day 183 at pre-exposure and 120 to 180 minutes after the start of cedar pollen exposure (5 samples 15 minutes apart)]

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.

Mesures de resultats secundaris

1. Change From Pre-Exposure in Mean Total 4 Nasal Symptom Score (4TNSS) 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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.

2. Change From Pre-Exposure in Sneezing Score 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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)

3. Change From Pre-Exposure in Nasal Discharge Score 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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)

4. Change From Pre-Exposure in Mean Nasal Congestion Score 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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)

5. Change From Pre-Exposure in Mean Itchy Nose Score 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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)

6. Change From Pre-Exposure in Mean Total Non-Nasal Symptom Score (TNNSS) 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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.

7. Change From Pre-Exposure in Mean Itchy Eyes Score 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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)

8. Change From Pre-Exposure in Mean Watery Eyes Score 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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)

9. Change From Pre-Exposure in Total 5 Symptom Score (5TSS) 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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.

10. Change From Pre-Exposure in Mean Total 6 Symptom Score (6TSS) 120 to 180 Minutes After Cedar Pollen Exposure [Pre-exposure and 120-180 minutes after the start of pollen exposure (5 samples 15 minutes apart) on Days 127, 155, and 183]

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.

11. Time to Occurrence of Nasal or Eye Symptom From Start of Cedar Pollen Exposure [Days 127, 155 and 183, from the start of cedar pollen exposure for up to 180 minutes]

Time point when the score of nasal or eye symptom worsens by 1 or more as compared to before cedar pollen exposure were assessed.

12. Amount of Nasal Discharge Per 30 Minutes During Cedar Pollen 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]

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.

13. Sneezing Count Per 30 Minutes During Cedar Pollen 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]

Sneezing count per 30 minutes were measured during chamber exposure.

14. Number of Participants With Adverse Events (AE) During the Primary Study Period [From first dose of study drug up to the end of primary study period (up to 7 days after Day 183)]

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

15. Number of Participants With Serious Adverse Events (SAE) During the Long-Term Safety Follow-Up Period [Up to 9 months after the end of primary study period (primary study period was up to 7 days after Day 183)]

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.