This study is designed to find out how effective and safe a new drug, GSK3862995B, is for adult participants with bronchiectasis, a chronic lung disease. The study will also test how the body processes the drug and to check for any immune reactions. Participants will be divided into groups randomly to receive either one of two different doses of the study drug or a placebo. The main goal of the study is to see how well the drug works compared to the placebo in helping those with bronchiectasis.

Inclusion Criteria:

• Body mass index (BMI) between 18-35 kilograms per square meters (kg/m^2)

• Clinical history consistent with bronchiectasis (cough, chronic sputum production, and/or recurrent respiratory infections) that is confirmed on chest computed tomography (CT)

• Meet one of the two criteria:

  • In the 12 months prior to screening, have had 2 or more documented pulmonary exacerbations that required a new antibiotic prescription by a physician or 1 pulmonary exacerbation that required hospitalization; or
  • In the 12 months prior to screening, have had 0 or 1 pulmonary exacerbation and a QOL-B RSS of less than (<)50 at screening

• Current sputum producers

• Post-bronchodilator FEV1 greater than or equal to (>=) 30 percent (%) or greater of predicted normal value

• Non-smokers or former cigarette smokers

• Males and females of childbearing and non-childbearing potential

• A female participant is eligible to participate if she is not pregnant or breastfeeding

• 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

• A WOCBP must have a negative highly sensitive serum pregnancy test within 28 days before the first dose of study intervention

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed consent form (ICF) and in this protocol

Exclusion Criteria:

• Participants with a primary diagnosis of asthma or Chronic Obstructive Pulmonary Disorder (COPD) as judged by the investigator
• Bronchiectasis due to cystic fibrosis, alpha-1-antitrypsin deficiency, common variable immunodeficiency, hypogammaglobinemia, or traction bronchiectasis due to fibrotic lung disease
• Active non-tuberculosis mycobacterial (NTM) lung infection on treatment or meeting ATS/Infectious Diseases Society of America (IDSA) criteria for active lung infection
• Active tuberculosis, untreated latent Tuberculosis (TB), invasive fungal lung infections or allergic bronchopulmonary aspergillosis needing treatment
• Participant uses long-term oxygen therapy for more than 12 hours per day
• Participants with an acute lower respiratory tract pulmonary infection needing treatment or pulmonary exacerbation within 4 weeks of the screening visit.
• Participant has a past or current medical condition(s) or disease(s) that is/are not well controlled and, which in the judgment of the Investigator, may affect participant safety or affect study endpoints
• Participants with an unstable cardiac disease, myocardial infarction, Cerebrovascular Accident (CVA), stroke or New York Heart Association Class III or IV heart failure within 12 months prior to screening
• Participants with clinically significant abnormal Electrocardiogram (ECG) at screening which in the judgment of the Investigator, may affect participant safety or affect study endpoints
• Significant allergies to humanized monoclonal antibodies
• Participants with a history of 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 for cure with no evidence of recurrence or metastatic disease for 1-year
• A known or suspected immunodeficiency that has led to opportunistic infections, recurrent invasive infections, or prolonged infections that suggest an underlying immunocompromised state by the judgement of the investigator. Positive HIV antibody test
• Alanine aminotransferase (ALT) >2x Upper limit of normal (ULN)
• Total bilirubin >1.5xULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5xULN as long as direct bilirubin is less than or equal to (<=)1.5xULN
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Presence of hepatitis B surface antigen (Hepatitis B surface antigen [HBsAg]) and/or hepatitis B core antibody (Hepatitis B core antibody [HBcAb]) at screening or within 3 months prior to first dose of study intervention
• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention
• Positive hepatitis C Hepatitis B core antibody (RNA) test result at screening or within 3 months prior to first dose of study intervention
• Corrected QT interval (QTc) >450 milliseconds (msec) at screening visit based on the average of triplicate ECGs The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

This is double-blind placebo-controlled study.