Phase 1, FTIH, Study to Evaluate the Safety, Tolerability, Blood Sample of Single Ascending Dose of GSK4771261 in Healthy Participants and Autosomal Dominant Polycystic Kidney Disease Participants

A Randomised, Double Blind, Placebo-controlled, Single Ascending Dose, Phase 1a/1b Multi-centre Study in Healthy Participants and Participants With Autosomal Dominant Polycystic Kidney Disease to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK4771261.

This is a study where a new drug, called GSK4771261 is being tested. Neither the study doctors, study staff or participants will be aware of what treatment is being given. Part A is testing the new study treatment on healthy people. This is to see if it's safe, what it does to the body, and how the body's defense system responds to it. Part B is similar, but the study treatment will be given to people who have a kidney disease called autosomal dominant polycystic kidney disease (ADPKD).

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Disease
• Intervention / Treatment: Drug: Placebo; Drug: GSK4771261

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

-For Part A and Part B: Body weight greater than or equal to (>=) 45 kilograms (kg) and basal metabolic index (BMI) within the range 19.5 to 32 kilograms per square meters (kg/m^2), inclusive Capable of giving signed informed consent, which includes compliance with the requirements and restrictions in listed in the informed consent form (ICF) and in the protocol

For Part A:

Participants who are overtly healthy as determined by medical evaluation by the investigator or a medically qualified designee based on medical history, physical examination, laboratory tests, and cardiac monitoring Women must be of non-childbearing potential

For Part B:

Confirmed diagnosis of Autosomal dominant polycystic kidney disease (ADPKD) by either applicable guidelines and/or genetic and imaging screening assessments Participants diagnosed with ADPKD may have complications or comorbidities directly related to ADPKD but should be otherwise healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests clinical testing per SoA Confirmation of known ADPKD causal genetic mutation(s) at the Polycystic kidney disease (PKD)1 and/or PKD2 loci based on genetic testing at screening Mayo imaging classification groups 1A, 1B, 1C, 1D or 1E as assessed using the information collected at screening Estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 60 millilitres per minutes per 1.73 square meters (mL/min/1.73m^2) (based on the Chronic kidney disease- Epidemiology Collaboration [CKD-EPI 2021] eGFR equation) and is not anticipated by the participant's regular treating physician to have a sustained decline by greater than (>)10 percent (%) over the following 12 months Intolerant of tolvaptan treatment, unwilling to initiate tolvaptan treatment or ineligible for tolvaptan treatment for ADPKD A female participant is eligible to participate if she is not pregnant or breastfeeding and agrees to use birth control methods as discussed with the study doctor.

Woman of childbearing potential (WOCBP) and Woman of non-childbearing potential (WONCBP) must have a negative highly sensitive pregnancy test prior to the Magnetic resonance imaging (MRI) scan being performed in the screening period of Part B A WOCBP and WONCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hr before the first dose of study intervention

Exclusion Criteria:

-For Part A: History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug; or interfering with the interpretation of data History of malignancy of any type History of kidney disease or kidney abnormalities or eGFR less than (<) 90 millilitres per minute per 1.73 square meters (mL/min/1.73m^2) (based on the chronic kidney disease- Epidemiology Collaboration [CKD-EPI] 2021 eGFR equation) at screening Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study drug and for the duration of study participation QTc >450 milliseconds (msec)

Part B:

Presence of active, clinically significant cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, or neurological disorders, with the exception of ADPKD, capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug; or interfering with the interpretation of data Clinically significant abnormal blood pressure (BP), that is, if the participant is not taking antihypertensive therapy: systolic BP >= 160 millimetres of mercury (mmHg) and/or diastolic BP >= 90mmHg; or If the participant is established on a stable regimen of antihypertensive drug(s): on-treatment systolic BP >= 160milimeters of mercury (mmHg) and/or diastolic BP >=90mmHg 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 recurrence or metastatic disease for 3 years Breast cancer within the past 10 years Use of prescription and non-prescription drugs, including vitamins A, B, C, E, K, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study drug and for the duration of study participation, and/or in consultation with the medical monitor. Paracetamol, at doses of <= 4 gram per 24 hour (g/24h) is permitted for use at any time during the study Contraindication to, or unwillingness to undergo, MRI scanning (e.g., presence of MRI-incompatible metal implant) Congenital absence of one kidney Kidney cyst interventions such as cyst aspiration or cyst fenestration within 12 weeks prior to screening and during the screening period, or such interventions planned or anticipated within the follow-up period Acute kidney cyst haemorrhage or infection within 12 weeks prior to screening Evidence of current, chronic, or recurrent kidney or liver cyst infection Estimated proteinuria >1g/24hr at screening and/or pre-dose (day -7 to day -1) Abnormal urinalysis suggestive of clinically significant glomerular disease or urinary tract infection Presence of known renal or hepatic calculi, or symptoms thereof, at screening Treatment with tolvaptan within 6 months prior to screening

Part A and Part B:

Participation in this study would result in loss of blood or blood products in excess of 500 mL within 56 days Current enrolment or past participation in an investigational clinical trial in which an investigational medicinal product was administered within the following time periods prior to the first dosing day of the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product, whichever is longer Exposure to more than 4 investigational medicinal products within 12 months prior to dosing Significant allergy to humanized monoclonal antibodies Clinically significant multiple or severe drug allergies, 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) Pregnant or lactating female Current or previous diagnosis of diabetes mellites (DM) (Type 1 or Type 2) Glycosylated hemoglobin (HbA1c) >= 48 millimoles per mole (mmol/mol) (>=6.5%) at screening Bone fracture within 6 months prior to screening, or presence of a known unresolved or incompletely resolved fracture Positive pre-clinical study drug/alcohol screen, including tetrahydrocannabinol Positive Human Immunodeficiency Virus (HIV) antibody test Evidence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by local diagnostic procedures Evidence at screening of clinically significant haematological disorder (affecting haemoglobin, red blood cells [RBC], White blood cells [WBC] or platelets) or abnormal blood clotting parameters Regular use of recreational drugs, including substances containing tetrahydrocannabinol Participants who are unable to refrain from smoking, vaping or using other tobacco products during study visits or overnight stays Poor peripheral venous access by visual inspection (intravenous [IV] administration cohort(s) only) Average weekly intake of greater than (>) 14 UK units of alcohol. One UK unit is equivalent to 8 grams of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 millilitres [mL]) of wine or 1 (25 mL) measure of spirits Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator [or medical monitor], contraindicates participation in the study Use of any products intended to treat medical conditions that are not approved by the governing health authority in a given country or region (for example, herbal medicine, health supplements, traditional medicine, homeopathic remedies, etc.) Alanine transaminase (ALT) >1.5x 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 <=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 (HBsAg) and/or 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 Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention QTc >450 milliseconds (msec) or QTc > 480 msec for participants with bundle branch block

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Cohort 1; Healthy participants will be randomized to receive GSK4771261 Dose 1.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part A: Cohort 2; Healthy participants will be randomized to receive GSK4771261 Dose 2.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part A: Cohort 3; Healthy participants will be randomized to receive GSK4771261 Dose 3.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part A: Cohort 4; Healthy participants will be randomized to receive GSK4771261 Dose 4.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part A: Cohort 5; Healthy participants will be randomized to receive GSK4771261 Dose 5.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part A: Cohort 6; Healthy participants will be randomized to receive GSK4771261 Dose 6.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part A: Cohort 7 (optional); Healthy participants will be randomized to receive GSK4771261 Dose 7 as the recommendation of Dose escalation committee (DEC).	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part A: Cohort 8 (optional); Healthy participants will be randomized to receive GSK4771261 Dose 8, as per the recommendation from DEC.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part B: Cohort 1; Participant with Autosomal dominant polycystic kidney disease (ADPKD) will be randomized to receive GSK4771261 Dose 9.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part B: Cohort 2; Participant with ADPKD will be randomized to receive GSK4771261 Dose 10.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part B: Cohort 3; Participant with ADPKD will be randomized to receive GSK4771261 Dose 11.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part B: Cohort 4 (optional); Participant with ADPKD will be randomized to receive GSK4771261 Dose 12 as the recommendation from DEC.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part B: Cohort 5 (optional); Participant with ADPKD will be randomized to receive GSK4771261 Dose 13, as per the recommendation from DEC.	Drug: GSK4771261; GSK4771261 will be administered.
Experimental: Part A and B: Placebo; Healthy participant and participants with ADPKD will be randomized to receive matching Placebo.	Drug: Placebo; Placebo will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of Participants with Adverse events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.	From Baseline (Day 1) up to Day 183 (End of study [EoS])
Part B: Number of Participants with Adverse events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.	From Baseline (Day 1) up to Day 183 (EoS)
Part A: Number of Participants with Serious Adverse Events (SAEs)	An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: results in death; is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant; abnormal pregnancy outcome (for example, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy); is a suspected transmission of any infectious agent via an authorized medicinal product; or other situations like Possible Hy's Law case/significant medical events that may jeopardize the participant or may require medical or surgical intervention.	From Baseline (Day 1) up to Day 183 (EoS)
Part B: Number of Participants with Serious Adverse Events (SAEs)	An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: results in death; is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant; abnormal pregnancy outcome (for example, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy); is a suspected transmission of any infectious agent via an authorized medicinal product; or other situations like Possible Hy's Law case/significant medical events that may jeopardize the participant or may require medical or surgical intervention.	From Baseline (Day 1) up to Day 183 (EoS)
Part A: Number of Participants with Clinically Significant Changes in Blood Laboratory Values	Number of participants with clinically significant changes in blood laboratory values will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part B: Number of Participants with Clinically Significant Changes in Blood Laboratory Values	Number of participants with clinically significant changes in blood laboratory values will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part A: Number of Participants with Clinically Significant Changes in Urine Laboratory Values	Number of participants with clinically significant changes in Urine laboratory values will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part B: Number of Participants with Clinically Significant Changes in Urine Laboratory Values	Number of participants with clinically significant changes in Urine laboratory values will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part A: Number of Participants with Clinically Significant Changes in Vital Signs	Number of participants with clinically significant changes in vital signs (tympanic temperature, Respiratory rate (RR), pulse rate and blood pressure) will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part B: Number of Participants with Clinically Significant Changes in Vital Signs	Number of participants with clinically significant changes in vital signs (tympanic temperature, Respiratory rate (RR), pulse rate and blood pressure) will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part A: Number of Participants with Clinically Significant Changes in 12-lead Electrocardiogram (ECG)	Number of participants with clinically significant changes in 12-lead ECG parameters (Heart rate PR, QRS, QT, and QTc intervals) will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part B: Number of Participants with Clinically Significant Changes in 12-lead Electrocardiogram (ECG)	Number of participants with clinically significant changes in 12-lead ECG parameters (Heart rate PR, QRS, QT, and QTc intervals) will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of Participants with Anti-drug Antibodies for GSK4771261.	Number of participants with Anti-drug antibodies for GSK4771261 will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part B: Number of Participants with Anti-drug Antibodies for GSK4771261.	Number of participants with Anti-drug antibodies for GSK4771261 will be evaluated.	From Baseline (Day 1) up to Day 183 (EoS)
Part A: Area Under Curve (AUC) of GSK4771261	Blood samples were collected to evaluate Plasms concentration of GSK4771261.	Day 1, 2, 3, 4, 5, 8 (For Intravenous [IV] administration), Day 1, 2, 3, 4, 5, 6, 7, 8 (For subcutaneous [SC] administration), and Day 15, 22, 29, 43, 57, 85, 113, 141, and 182, (EoS) (for both IV and SC administration)
Part B: Area Under Curve (AUC) of GSK4771261	Blood samples were collected to evaluate Plasms concentration of GSK4771261.	Day 1, 2, 8, 15, 29, 43, 85, 113, 141, and 182, (EoS)
Part A: Maximum Plasma Concentration (Cmax) of GSK4771261	Blood samples were collected to evaluate Plasms concentration of GSK4771261.	Day 1, 2, 3, 4, 5, 8 (For Intravenous [IV] administration), Day 1, 2, 3, 4, 5, 6, 7, 8 (For subcutaneous [SC] administration), 15, 22, 29, 43, 57, 85, 113, 141, and 182 (EoS) (for both IV and SC administration)
Part B: Maximum Plasma Concentration (Cmax) of GSK4771261	Blood samples were collected to evaluate Plasms concentration of GSK4771261.	Day 1, 2, 8, 15, 29, 43, 85, 113, 141, and 182 (EoS)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): December 11, 2024
• Primary Completion (Estimated): July 23, 2026
• Study Completion (Estimated): August 20, 2026

Study Registration Dates

• First Submitted: October 1, 2024
• First Submitted That Met QC Criteria: October 1, 2024
• First Posted (Estimated): October 3, 2024

Study Record Updates

• Last Update Posted (Estimated): October 3, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Immunogenicity; Phase 1; Tolerability; Pharmacodynamics; GSK4771261; Autosomal dominant polycystic kidney disease (ADPKD)
• Additional Relevant MeSH Terms: Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
• Other Study ID Numbers: 221362; 2024-516095-15 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: GSK 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
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No