Clinical trial NCT04184895: A Study to Assess the Safety, Tolerability and Immunological Response of ASP2390 in Adult Subjects Allergic to House Dust Mites
Official title: A Phase 1 Multiple Ascending Intradermal Dose Study to Assess the Safety, Tolerability and Immunological Response of ASP2390 in Adult Subjects Allergic to House Dust Mites
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Allergic to House Dust Mites
Keywords: Tolerability
HDM
ASP2390
Safety
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2019-12-04
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of multiple ascending intradermal doses of ASP2390 in adult male and female participants allergic to house dust mites (HDM).

This study will also evaluate the effect of multiple ascending intradermal doses of ASP2390 on HDM-specific immunoglobulin G subclass 4 (IgG4) levels in adult male and female participants allergic to HDM.

Detailed description: Screening will occur up to 6 weeks prior to enrollment. Eligible participants will return to the clinical unit on day -1 (if required by the clinical unit to facilitate the severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2\] real-time reverse transcription polymerase chain reaction \[PCR\] procedure) or on day 1.

After the first dose on day 1, all participants will remain in the clinical unit for observation for approximately 24 hours postdose. After the 24 hours, participants will be discharged from the clinical unit provided no reactions have occurred that require additional observation.

For all subsequent doses, participants will remain under direct observation for a minimum of 1 hour postdose. Participants will be discharged from the clinical unit provided no reactions have occurred that require additional observation.

Eligibility criteria: Inclusion Criteria:

* Subject has a history of house dust mite (HDM) induced allergic rhinitis with or without conjunctivitis of 1 year or longer in duration at screening 1.
* Subject has positive skin prick test (SPT) to D. pteronyssinus.
* Subject has a serum specific immunoglobulin E (IgE) level to D. pteronyssinus at screening 1 or within the past 12 months (if performed and documented at the clinical unit).
* Subject shows a positive symptomatic reaction to an HDM based on total nasal symptom score (TNSS) during the challenge test at screening 2.
* Subject has a forced expiratory volume in 1 second (FEV1) of 80% of predicted value or greater at screening 1.
* Subject has a body mass index (BMI) range of 18.5 to 35.0 kg/m2, inclusive and weighs at least 50 kg at screening 1.
* A female subject is eligible to participate if the female subject is not pregnant and at least 1 of the following conditions applies:

  * Not a woman of childbearing potential (WOCBP), OR
  * WOCBP who agrees to follow the contraceptive guidance starting at screening 1 and throughout the initial safety follow-up period.
* Female subject must agree not to breastfeed starting at screening 1 and throughout the initial safety follow-up period.
* Female subject must not donate ova starting at screening 1 and throughout the initial safety follow-up period.
* A male subject with female partner(s) of childbearing potential must agree to use contraception until after completion of the initial safety follow-up period.
* A male subject must not donate sperm until after completion of the initial safety follow-up period.
* Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner(s) is(are) breastfeeding until after completion of the initial safety follow-up period.
* Subject agrees not to participate in another interventional study while receiving study drug in present study and until after completion of the initial safety follow-up period.

Exclusion Criteria:

* Subject with concomitant allergies to seasonal aeroallergens which are anticipated to be or become active through the completion of the week 18 daily symptom diary.
* Subject with a concomitant allergy to an animal dander who has exposure on a regular basis to the respective animal dander.
* Subject has received immunosuppressive treatment within 3 months prior to screening 1.
* Subject has received previous immunotherapy treatment with any HDM allergen within 3 years prior to screening 1.
* Subject is receiving ongoing treatment with any specific immunotherapy for other allergies or plans to receive during the course of the primary study period.
* Subject who has used systemic (or inhaled) steroid, mast cell stabilizing drug, T-helper cell type 2 (Th2) cytokine inhibitor, thromboxane A2 synthesis inhibitor, thromboxane A2 receptor antagonist, β-blocker, α-adrenergic blockers, ergot alkaloids, angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers within 2 months prior to first study drug administration.
* Subject who has used biologics that are immune modulators within 3 months prior to first study drug administration.
* Subject who has received or is planning to receive vaccination of a live vaccine within 28 days prior to the first administration of the study drug and/or subject who has received or is planning to receive vaccination of an inactive vaccine/toxoid within 7 days prior to the first administration of the study drug during the primary study period.
* Subject with mild to severe asthma receiving therapy.
* Subject has a nasal condition that could confound the efficacy or safety assessments.
* Subject who has history of allergic reactions such as anaphylactic shock, exanthema generalized, angioedema or hypotension caused by HDM and/or any medical products (including vaccine) in the past.
* Subject who has immune disorders and/or diseases requiring immunosuppressive drugs.
* Subject who was diagnosed with immunodeficiency in the past.
* Subject who is unable to discontinue antihistamines.
* Subject has received investigational study drug within 28 days or 5 half-lives, whichever is longer, prior to screening 1.
* Subject has a known or suspected intolerance to lactose and/or milk products.
* Subject has used any prescribed or nonprescribed drugs in the 2 weeks prior to first study drug administration, except for occasional use of paracetamol, topical dermatological products, hormonal contraceptives or hormone replacement therapy (HRT), beta-2-agonist for treatment of asthma or rescue medications for rhinitis and for conjunctivitis, or the coronavirus disease 2019 (COVID-19) vaccine within 7 days prior to the first study drug administration.
* Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to screening 1.
* Subject has a history of drinking more than 21 units of alcohol per week (\> 14 units of alcohol for female subjects) within 3 months prior to screening 1 or the subject tests positive for alcohol or drugs of abuse
* Subject has had significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to screening 1.
* Other exclusion criteria apply.
* Subject has a positive result for SARS-CoV-2 PCR test prior to the chamber challenge at screening 2 (repeat virus testing performed 4 to 7 days apart with the second PCR test to be performed a maximum of 2 days prior to the chamber challenge at screening 2) or prior to randomization on day 1.
* Subject has clinical signs and symptoms consistent with COVID-19 infection, e.g., fever, dry cough, dyspnea, sore throat, fatigue, muscle or body aches and gastrointestinal symptoms or confirmed infection by appropriate SARS-CoV-2 PCR test within the 4 weeks prior to screening 1.

Primary outcomes:
measure: Number of participants with Adverse Events (AEs)
timeFrame: Up to week 63
measure: Number of participants with laboratory value abnormalities and/or AEs
timeFrame: Up to week 63
measure: Number of participants with vital sign abnormalities and/or AEs
timeFrame: Up to week 63
measure: Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs
timeFrame: Up to week 63
measure: Number of participants with subcutaneous immunotherapy systemic reaction events
timeFrame: Up to week 11
measure: Number of participants with specific local reactogenicity events
timeFrame: Up to week 12
measure: Number of participants with specific systemic reactogenicity events
timeFrame: Up to week 12
Secondary outcomes:
measure: Change from baseline in immunological response to ASP2390 as assessed by HDM allergen-specific IgG4 levels
timeFrame: Baseline and up to week 24
measure: Number of participants with Adverse Events
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Site DE49001
city: Hannover
country: Germany
facility: Site DE49002
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Senior Medical Director
role: STUDY_DIRECTOR
References: