Clinical trial NCT06154837: A Study for GSK3862995B in Healthy Participants and Participants With Chronic Obstructive Pulmonary Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: GSK3862995B
Chronic Obstructive Pulmonary Disease
Phase 1
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2023-12-04
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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).
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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 (\>=) 40% 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/microliter (mcL) at screening
* Former cigarette smokers with a history of cigarette smoking of \>=10 pack-years at screening current smokers (includes the use of any type of nicotine containing product), or non-smokers are permitted
* 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).

Primary outcomes:
measure: Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 36 weeks
measure: Part B: Number of Participants with AEs and SAEs
timeFrame: Up to 48 weeks
measure: Part A: Number of Participants with Clinically significant changes in laboratory values
timeFrame: Up to 28 weeks
measure: Part A: Number of Participants with Clinically Significant Change in vital signs
timeFrame: Up to 28 weeks
measure: Part A: Number of Participants with Clinically Significant Change in 12-lead Electrocardiogram (ECG) Parameters
timeFrame: Up to 28 weeks
measure: Part B: Number of Participants with Clinically significant changes in laboratory values (haematology, chemistry and urinalysis)
timeFrame: Up to 42 weeks
measure: Part B: Number of Participants with Clinically Significant Change in vital signs
timeFrame: Up to 42 weeks
measure: Part B: Number of Participants with Clinically Significant Change in 12-lead Electrocardiogram (ECG) Parameters
timeFrame: Up to 42 weeks
Secondary outcomes:
measure: Part A: Area Under the Concentration-time Curve to the Last Quantifiable Concentration [AUC(0-t)]
timeFrame: Up to 28 weeks
measure: Part A: Area Under the Concentration-time Curve to the Infinity (inf) [AUC(0-inf)]
timeFrame: Up to 28 weeks
measure: Part A: Maximum Concentration (Cmax)
timeFrame: Up to 28 weeks
measure: Part B: Area Under the Concentration-time Curve Over the Dosing Interval [AUC(0-tau)]
timeFrame: Up to 42 weeks
measure: Part B: Cmax
timeFrame: Up to 42 weeks
measure: Part A: Number of Participants with Anti-Drug Antibodies (ADA) against GSK3682995B
timeFrame: Up to 28 weeks
measure: Part B: Number of participants with Incidence of Anti-Drug Antibodies (ADA) against GSK3682995B
timeFrame: Up to 42 weeks
measure: Part A: Ratio to Baseline in Absolute and Relative Blood Eosinophil Count
timeFrame: Baseline and up to 28 weeks
measure: Part B: Ratio to Baseline in Absolute and Relative Blood Eosinophil Count
timeFrame: Baseline and up to 42 weeks
Other outcomes:
Locations:
city: Rock Hill
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Dresden
country: Germany
facility: GSK Investigational Site
city: Luebeck
country: Germany
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
city: Barnsley
country: United Kingdom
facility: GSK Investigational Site
city: Blackpool
country: United Kingdom
facility: GSK Investigational Site
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
city: Cannock
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: West Yorkshire
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: