A Study for GSK3862995B in Healthy Participants and Participants With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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The primary objective of the study is to investigate the safety and tolerability of ascending doses of GSK3862995B following single dose in healthy participants and repeat doses in participants with Chronic obstructive pulmonary disease (COPD).

Official Title
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A Two-part Phase 1 Randomized, Double-blind, Placebo-controlled Study to Investigate Safety, Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of GSK3862995B Following Single Ascending Doses in Healthy Participants and Repeat Doses in Participants With Chronic Obstructive Pulmonary Disease

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: GSK3862995B
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants (Part A) Participant must be 18 to 65 years of age inclusive. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring Body weight within the range 50-110 kilogram (kg) (inclusive) Body mass index (BMI) within the range 19.5-32 kilogram per square meter (kg/m^2) Male and/or female of non-childbearing potential Participants with Chronic Obstructive Pulmonary Disorder (COPD) (Part B) Participant must be 40 to 75 years of age inclusive. Body weight within the range 50-110 kg (inclusive) BMI within the range 19.5-32 kg/m^2 Participant has a confirmed diagnosis of COPD for greater than (>)12 months Participants must present with a measured post-salbutamol Forced expiratory volume in 1 second/Forced vital capacity (FEV1/FVC) ratio of less than (<) 0.70 at screening to confirm the diagnosis of COPD and a measured post-salbutamol FEV1 greater than or equal to (>=) 50% of predicted normal values. Participants must have a well-documented requirement for optimized standard of care background therapy that includes daily inhaled medication. A peripheral blood eosinophil count of ≥150 cells/mcL at screening Former cigarette smokers with a history of cigarette smoking of >=10 pack-years at screening Male and/or female of non-childbearing potential. Exclusion Criteria: Participant has a past or current medical condition(s) or disease(s) that is/are not well controlled and, which in the judgement of the Investigator, may affect participant safety or affect study endpoints. A history of recurrent infections, or treatment of a chronic infection within 3 months prior to the first dose of study drug, including both serious local infection (for example, cellulitis, abscess) or systemic infection (for example, pneumonia, tuberculosis, hepatitis B, shingles). Significant allergies to humanized monoclonal antibodies. Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis). Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Breast cancer within the past 10 years Alanine transaminase (ALT) >1x upper limit of normal (ULN) Total bilirubin >1.5xULN (isolated total bilirubin >1.5xULN is acceptable if total bilirubin is fractionated and direct bilirubin less than (<) 35%). Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). A clinically significant abnormality in 12-lead ECG readings performed at screening A clinically significant abnormality in the Holter monitor performed at screening (IV cohorts only).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The primary purpose of the study is to evaluate the safety, and tolerability of GSK3862995B following single dose in healthy participants and repeat doses in participants with Chronic obstructive pulmonary disorder (COPD).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Single ascending dose (SAD) of GSK3862995B<br>Healthy participants will receive GSK3862995B. | Drug: GSK3862995B<br>* GSK3862995B will be administered.<br>|
| Experimental: Part B: Repeat doses GSK3862995B<br>Participants with COPD will receive repeat doses of GSK3862995B. | Drug: GSK3862995B<br>* GSK3862995B will be administered.<br>|
| Experimental: Part B: Placebo<br>Participants with COPD will receive repeat doses of Placebo. | Drug: Placebo<br>* Placebo will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE. | Up to 36 weeks | 
| Part B: Number of Participants with AEs and SAEs | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE. | Up to 48 weeks | 
| Part A: Number of Participants with Clinically significant changes in laboratory values | Number of Participants with clinically significant changes in laboratory values (haematology, chemistry, and urinalysis) will be assessed. | Up to 28 weeks | 
| Part A: Number of Participants with Clinically Significant Change in vital signs | Number of participants with clinically significant change in vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure) will be assessed. | Up to 28 weeks | 
| Part A: Number of Participants with Clinically Significant Change in 12-lead Electrocardiogram (ECG) Parameters | Number of participants with clinically significant change in 12-lead ECG parameters will be assessed. | Up to 28 weeks | 
| Part B: Number of Participants with Clinically significant changes in laboratory values. (haematology, chemistry and urinalysis) | Number of Participants with clinically significant changes in laboratory values (haematology, chemistry and urinalysis) will be assessed. | Up to 40 weeks | 
| Part B: Number of Participants with Clinically Significant Change in vital signs | Number of participants with clinically significant change in vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure) up to end of intervention period will be assessed. | Up to 40 weeks | 
| Part B: Number of Participants with Clinically Significant Change in 12-lead Electrocardiogram (ECG) Parameters | Number of participants with clinically significant change in 12-lead ECG parameters will be assessed. | Up to 40 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Area Under the Concentration-time Curve to the Last Quantifiable Concentration [AUC(0-t) | Blood samples were collected at the indicated time points for pharmacokinetic (PK) analysis. PK parameters were calculated by standard non-compartmental analysis. | Up to 28 weeks | 
| Part A: Area Under the Concentration-time Curve to the Infinity (inf) [AUC(0-inf) | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Up to 28 weeks | 
| Part A: Maximum Concentration (Cmax) | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Up to 28 weeks | 
| Part B: Area Under the Concentration-time Curve Over the Dosing Interval [AUC(0-tau) | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Up to 40 weeks | 
| Part B: Cmax | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Up to 40 weeks | 
| Part A: Number of Participants with Anti-Drug Antibodies (ADA) against GSK3682995B | Blood samples were analyzed for the presence of anti- GSK3682995B antibodies by binding ADA assay. | Up to 28 weeks | 
| Part B: Number of participants with Incidence of Anti-Drug Antibodies (ADA) against GSK3682995B | Blood samples were analyzed for the presence of anti-GSK3682995B antibodies by binding ADA assay. | Up to 40 weeks | 
| Part A: Change From Baseline in Absolute and Relative Blood Eosinophil Count | Change from baseline in absolute and relative blood eosinophil count will be assessed. | Baseline and up to 28 weeks | 
| Part B: Change From Baseline in Absolute and Relative Blood Eosinophil Count | Change from baseline in absolute and relative blood eosinophil count will be assessed. | Baseline and up to 40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK3862995B, Chronic Obstructive Pulmonary Disease, Phase 1