Clinical trial NCT05794672: A Study to Investigate the Safety, Tolerability and Pharmacokinetics of Elarekibep in Healthy Japanese Subjects
Official title: A Phase 1, Randomised, Single-blind, Placebo-controlled, Single-centre Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of Elarekibep Given Twice Daily as Inhaled or a Single IV Formulation in Healthy Japanese Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Subjects (Indication: Asthma)
Keywords: Heterogenous respiratory disease
Pulmonary inflammation
Healthy subjects
Japanese subjects
Interleukin 4 receptor alpha antagonist
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2023-04-03
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the safety, tolerability and pharmacokinetics (PK) of elarekibep after single and multiple doses given twice daily (BID) by inhalation or intravenous (IV) in healthy Japanese subjects compared with placebo.

Detailed description: This is a Phase I, randomised, single-blind, placebo-controlled, single-centre study. This study comprises upto a total of 42 subjects.

This study consists of two parts: A single dose part (Part A1 and Part A2) and a multiple dose part (Part B).

Part A and Part B will comprise of the following:

* Each subject will be involved in the study for up to 9 weeks if enrolled in Part A and up to 10 weeks if enrolled in Part B.
* A screening period of maximum 28 days.
* Treatment period: Part A: Study treatment Day 1; Part B: Study treatment Days 1 to 6 and a single inhaled dose on Day 7.
* A safety follow-up call will be conducted 7 (± 1) days after elarekibep or placebo administration.
* A safety follow-up visit will be conducted 30 (± 2) days after elarekibep or placebo administration in each cohort.

Eligibility criteria: Inclusion Criteria:

* Subject must be aged 20 to 55 years.
* Subject must have a Body Mass Index (BMI) between 18 and 35 kg/m2 and weigh a minimum of 48 kg.
* First generation subjects who were born in Japan and who have both parents and grandparents of Japanese descent.
* All females must have a negative pregnancy test at the Screening Visit (serum) and on admission (urine) to the Clinical Unit and must not be lactating or planning to become pregnant.
* Subjects who are non-smokers or ex-smokers who have smoked no more than twice in the 3 months preceding the first dose of study drug.
* Must be able to demonstrate proper inhalation technique using the monodose Dry Powder Inhaler (DPI) device.
* Able to perform acceptable pulmonary function testing for Forced Expiratory Volume in one second (FEV1) according to American Thoracic Society (ATS)/European Respiratory Society (ERS) acceptability criteria.

Exclusion Criteria:

* History or clinical manifestations of any clinically significant medical disorder which may either put the subject at risk because of participation in the study, influence the results, or affect the subject's ability to participate in the study.
* History or presence of gastrointestinal, hepatic or renal disease.
* Any clinically significant illness, infection, medical/surgical procedure, or trauma within 4 weeks of Day 1 or planned in-patient surgery or hospitalization during the study period.
* Diagnosis of Sjögren's syndrome.
* Any laboratory values with deviations from the study's laboratory parameters.
* Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).
* Any clinically important abnormalities in rhythm, conduction or morphology of the resting Electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG.
* Known or suspected history of drug abuse in the last 5 years.
* Known or suspected history of alcohol abuse or excessive intake of alcohol in the last 2 years.
* Positive screen for drugs of abuse, alcohol or cotinine at the Screening Visit.
* History of anaphylaxis following any biologic therapy or vaccine and known history of allergy or reaction to any component of the Investigational Medicinal Product (IMP) formulation.
* Plasma donation within 1 month of the Screening Visit or any blood donation/blood loss \> 450 mL during the 3 months prior to the Screening Visit.
* Excessive intake of caffeine containing drinks or food.
* Participation in more than 4 clinical studies with IMPs in the last year.
* Involvement of subjects who have a significant history of recurrent or ongoing dry eye syndrome of any cause that may be chronic or acute and that may affect the interpretation of safety data associated with the potential for ADAs targeted to elarekibep.
* Subjects with a positive diagnostic nucleic acid test (using Polymerase Chain Reaction \[PCR\]) and/or rapid antigen test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) at screening and up to randomisation.
* Diagnosis of/suspected COVID-19 infection with associated pneumonia/pneumonitis.
* Receipt of COVID-19 vaccine (vaccine or booster dose) within 30 days prior to randomisation.
* History of anaphylaxis to any biologic therapy or vaccine.
* History of hypersensitivity that required the use of epinephrine or hospitalization.
* Known history of allergy or reaction to any component of the IMP formulation.
* History of allergic conjunctivitis and/or dry eye syndrome.
* Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to screening.
* History of cancer within the last 10 years except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured. Any history of lymphoma is not allowed.
* Males who are sexually active with a female partner of childbearing potential and who have not had a vasectomy and who do not agree to comply with highly effective methods of contraception from Day 1 until 90 days after the last dose of IMP.

Primary outcomes:
measure: Incidence of Adverse events
timeFrame: Up to Follow-up [Part A: 60 days, Part B: 67 days)
measure: Collection of blood samples for the measurement of safety immunobiomarkers
timeFrame: Part A: Screening (Day -28) to Day 3; Part B: Screening (Day -28 to -2) to Follow-up ([Day 37 ± 2)]
Secondary outcomes:
measure: Maximum observed serum (peak) drug concentration [Cmax]
timeFrame: Part A: Day 1 to Day 3, Part B: Day 1 to Day 9
measure: Area under the serum concentration curve from zero to the last quantifiable concentration (AUClast)
timeFrame: Part A: Day 1 to Day 3, Part B: Day 1 to Day 9
measure: Area under serum concentration time curve from zero to infinity (AUCinf)
timeFrame: Day 1
measure: Presence of elarekibep Antidrug Antibody (ADA)
timeFrame: Part A: Day 1; Part B: Day 1, Day 14 to Follow-up/ETV ([Day 37 ± 2)
measure: Standardised taste questionnaires
timeFrame: Part A: Day 1, Part B: Day 1
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
References: