Clinical trial NCT06979323: Depemokimab Asthma Imaging and Bronchoscopy Sub-Study
Official title: The IMAGINE Study: A Phase 3b Open Label, Single Arm Study to Assess the Effect of Depemokimab on Airway Structure and Function in Asthma With Type 2 Inflammation Characterized by an Eosinophilic Phenotype Utilizing Quantitative High-resolution CT and Bronchoscopic Airway Sampling in a Sub Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Asthma
Keywords: Depemokimab
Asthma
Type 2 Inflammation
Eosinophilic Phenotype
High Resolution Computed Tomography (HRCT)
Bronchoscopy
IMAGINE study
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2025-05-18
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single arm study
Primary purpose: TREATMENT

Brief summary: Asthma is a chronic condition marked by narrowed and swollen airways due to inflammation leading to recurring symptoms that can vary and worsen unpredictably. The purpose of this study is to assess how depemokimab, a monoclonal antibody, affects the structure and function of the lungs in asthmatic participants with type 2 inflammation, characterized by an eosinophilic phenotype.


Eligibility criteria: Inclusion Criteria:

* Documented physician diagnosis of asthma for greater than or equal to (\>=) 2 years as per the National Heart, Lung, and Blood Institute guidelines (NHLBI, 2020) or GINA guidelines along with the following: A T2 phenotype as evidenced by a blood eosinophil count of \>=300 cells/microliters (mcL) at screening or a documented history of blood eosinophil count \>=300 cells/mcL within 3 months prior to screening and Exhaled nitric oxide (FeNO) measure of \>=25 parts per billion (ppb) recorded at screening;
* \>= 2 exacerbations requiring treatment with systemic corticosteroid (SCS; intramuscular \[IM\], intravenous \[IV\], or oral), in the 12 months prior to screening, despite the use of medium to high dose Inhaled corticosteroids (ICS)
* Uncontrolled asthma indicated by Astha Control Questionnaire-5 (ACQ-5) greater than (\>) 1.5 recorded at screening
* Persistent airflow obstruction as indicated by pre-bronchodilator Forced Expiration Volume in 1 second (FEV1) less than (\<) 80 percentage (%) predicted (GLI 2012) and recorded at screening
* A well-documented requirement for regular treatment with medium or high dose ICS (in the 12 months prior to screening with or without maintenance oral corticosteroids \[OCS\])
* Current treatment with at least one additional asthma controller medication, besides ICS, for at least 3 months \[for example, Long-acting Beta 2 agonists \[LABA\], Long-acting muscarinic antagonists \[LAMA\], leukotriene receptor antagonist (LTRA), or theophylline\]
* Male Participants: No additional requirements for male participants
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: is a woman of non-childbearing potential (WONCBP) or is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency,
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention
* Capable of giving written informed consent,
* For the biopsy sub study participants who sign the Informed Consent for the bronchoscopy sub study, the following additional eligibility criteria will apply:

  * Participants not on maintenance OCS (oral corticosteroids) at the time of screening.
  * Participants with post bronchodilator FEV1 \>= 50% predicted
  * Participants with no known increased risk for bleeding or clotting abnormalities including: No history of easy bleeding, bruising or known bleeding diathesis; No current anticoagulant and antiplatelet therapy; No acetylsalicylic acid use within 2 weeks of the planned procedure; Normal screening platelet count
  * Participants with no specific contraindication to bronchoscopy with endobronchial biopsy in the opinion of the investigator
  * No history of allergic reaction to local anesthesia or general anesthetic agent, whichever is relevant to the procedure being performed

Exclusion Criteria:

* Presence of a known pre-existing, clinically important lung condition other than asthma. This includes (but is not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or a history of lung cancer. Participants with current diagnoses of emphysema or chronic bronchitis (Chronic obstructive pulmonary disease \[COPD\] other than asthma) are excluded
* Participants with other conditions that could lead to elevated eosinophils such as hyper eosinophilic syndromes including (but not limited to) Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or eosinophilic esophagitis
* Participants who developed an exacerbation within 4 weeks before screening
* Participants with a known, pre-existing parasitic infestation within 6 months prior to screening unless treated and evidenced to have been resolved
* A known immunodeficiency (e.g. human immunodeficiency virus HIV), other than that explained by the use of corticosteroids (CSs) taken as therapy for asthma
* A current malignancy or previous history of cancer in remission for less than 12 months prior to screening
* Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, psychiatric, renal, gastrointestinal, hepatic, hematologic or any other system abnormalities that are uncontrolled with standard treatment
* Participants with current diagnosis of vasculitis
* Participants who have received mepolizumab, reslizumab, or benralizumab within 12 months prior to screening or who have a previous documented failure with anti-IL-5/5R therapy
* Participants who have received omalizumab (Xolair), dupilumab (Dupixent) or tezepelumab (Tezspire) within 12 months prior to the screening
* Participants who have received any monoclonal antibody (mAb) within 5 half-lives of the drug prior to the screening. Authorized treatments for Coronavirus disease-2019 (COVID-19) are permitted
* Participants who have received treatment with an investigational drug within the past 30 days or 5 terminal phase half-lives of the drug whichever is longer, prior to the first dose of study intervention (this also includes investigational formulations of marketed products)
* Previously participated in any clinical study with biologic treatments for asthma (for example, omalizumab, mepolizumab, dupilumab, reslizumab, benralizumab, other mAbs (including Tezepelumab) or depemokimab and received study intervention (including placebo) within 12 months prior to the first dose of study intervention
* A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to the first dose of study intervention
* Current smokers or former smokers with a smoking history \>=20 pack years (number of pack years = \[number of cigarettes per day/20\] x number of years smoked) and vapers
* Participants with allergy/intolerance to a mAb or biologic or any of the excipients of depemokimab
* Participants who are pregnant or breastfeeding
* Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations
* Participants who have occupational ionizing-radiation exposure exceeding 10 Millisievert (mSV) over 3 years as documented with a dosimeter; have been exposed to elevated ionizing radiation from research imaging studies, for example, Participation in a research study with a single positron emission tomography scan in the past 3 years, and Participation in a research study with 2 or more computed tomography (CT) scans in the past 3 years in the following anatomical regions: chest, abdomen, cardiac, or spine
* Presence of metal objects that may interfere with chest CT quantification including presence of a cardiac pacemaker, defibrillator, metal prosthetic heart valve, metal projectile or metal weapon fragment (bullet, shrapnel, shotgun shot) or metal shoulder prosthesis
* Evidence of clinically significant abnormality in the hematological, biochemical or urinalysis screen at screening (Visit 0), as judged by the investigator

Primary outcomes:
measure: Mean Change from Baseline in Total Mucus Plug Volume Measured at Total Lung Capacity (TLC) at Week 26
timeFrame: From Baseline up to Week 26
Secondary outcomes:
measure: Mean Change from Baseline in Airway Wall Thickness Measured at TLC at Week 52
timeFrame: From Baseline up to Week 52
measure: Mean Change from Baseline in Airway Wall Thickness Measured at TLC at Week 26
timeFrame: From Baseline up to Week 26
measure: Mean Change from Baseline in Total Mucus Plug Volume Measured at TLC at Week 52
timeFrame: From Baseline up to Week 52
measure: Mean Change from Baseline at Week 26 for Mucus Segment Score
timeFrame: From Baseline up to Week 26
measure: Mean Change from Baseline at Week 52 for Mucus Segment Score
timeFrame: From Baseline up to Week 52
measure: Mean Change from Baseline in Pre- and Post- Bronchodilator Forced Expiration Volume in 1 second (BD FEV1) at Week 26
timeFrame: From Baseline up to Week 26
measure: Mean Change from Baseline in Pre- and Post-BD FEV1 at Week 52
timeFrame: From Baseline up to Week 52
measure: Number of Participants with Adverse Events (AE)
timeFrame: Up to Week 65 (End of Study)
measure: Number of Participants with Serious Adverse Events (SAE)
timeFrame: Up to Week 65 (End of Study)
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: