Placebo-controlled efficacy and safety study of GSK3511294 (depemokimab) in participants with severe asthma with an eosinophilic phenotype

Phase 1

Conditions: Severe uncontrolled asthma with an eosinophilic phenotype
MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2020-003632-25-IE

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 375

Inclusion Criteria

1.Age: Adults and adolescents =12 years of age, at the time of signing the informed consent/assent. [For countries where local regulations or the regulatory status of study medication permit enrolment of adults only, participants recruited will be =18 years of age]
Note: UK, Russia and German Participants: In UK, Russia and Germany only adult participants (=18 years) are to be included in this clinical trial.
2.Asthma: Participants must have a documented physician diagnosis of asthma for =2 years that meets the National Heart, Lung, and Blood Institute guidelines [NHLBI, 2007] or GINA guidelines [GINA, 2020] AND
a) Eosinophilic phenotype: Have, or with high likelihood of having, asthma with an eosinophilic phenotype as per Randomisation Criteria 1 and 2 (see
Section 5.3 of the protocol)
AND
b) Exacerbation history: Have previously confirmed history of =2 exacerbations requiring treatment with systemic cortiscosteroids (CS) (IM, IV, or oral), in the 12 months prior to Visit 1, despite the use of medium to high-dose inhaled cortiscosteroids ( ICS) (see criterion 4). For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.
3. Airflow obstruction: Persistent airflow obstruction as indicated by:
a) For participants =18 years of age at Visit 1, a pre-bronchodilator FEV1 <80% predicted (NHANES III) recorded at Visit 1
b) For participants 12-17 years of age at Visit 1:
• A pre-bronchodilator FEV1 <90% predicted (NHANES III) recorded at Visit 1 OR
• FEV1:Forced Vital Capacity (FVC) ratio <0.8 recorded at Visit 1
4. Inhaled Corticosteroid: A well-documented requirement for regular treatment with medium to high dose ICS (in the 12 months prior to Visit 1 with or without maintenance OCS). The maintenance ICS dose must be =440 mcg FP HFA daily, or clinically comparable [GINA, 2020; see Appendix 10 of the protocol]. Participants who are treated with medium dose ICS will also need to be treated with Long-acting beta-agonist (LABA) to qualify for inclusion.
5. Additional Controller Medication: Current treatment with at least one additional controller medication, besides ICS, for at least 3 months [e.g., LABA, long-acting muscarinic antagonist (LAMA), leukotriene receptor antagonist (LTRA), or theophylline].
6. Male or eligible female.
•A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
o Is a woman of non-childbearing potential (WONCBP) as defined in Section 10.4.1 of the protocol
OR
o Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.4.2 of the protocol from at least 14 days prior to the first dose of study intervention until at least 30 weeks after the last administered dose of study intervention.
• A WOCBP must have a negative highly sensitive serum pregnancy test at screening Visit 1 and a negative highly sensitive urine pregnancy test within
24 hours before the first dose of study intervention. Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.5. of the protocol.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, rec

Exclusion Criteria

1. Concurrent Respiratory Disease: 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 diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
2. Eosinophilic Diseases: 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.
3. Parasitic infection: Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1.
4. Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of CSs taken as therapy for asthma.
5. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localised carcinoma of the skin which was resected for cure will not be excluded).
6.Liver Disease: Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy,coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice.
NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) are acceptable if participant otherwise meets entry criteria.
7.Other Concurrent Medical Conditions: Participants who have known, preexisting, clinically significant cardiac, endocrine, autoimmune, metabolic,
neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
8. Vasculitis: Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment.
9.COVID-19: Participants that, according to the investigator's medical judgment, are likely to have active COVID-19 infection should be excluded. Participants with known COVID-19 positive contacts within the past 14 days should be excluded for at least 14 days following the exposure during which the participant should remain symptom-free.
10.Monoclonal antibodies targeting IL-5/5R: Participants who have received mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), or benralizumab
(Fasenra) within 12 months prior to Visit 1 or who have a previous documented failure with anti-IL-5/5R therapy.
11.Other mAbs in the treatment of asthma: Participants who have received omalizumab (Xolair) or dupilumab (Dupixent) within 130 days prior to Visit 1.
12.Other mAbs not used for the treatment of asthma: Participants who have received any mAb within 5 half-lives of Visit 1. Authorized
treatments for COVID-19 are permitted.
13.Investigational Medications: Participants who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to Visit 1 (this also includes investigational formulations of marketed products).
14. Previous participation: Previously participated in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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