A Study to Evaluate the Safety, Tolerability, and Effects on Blood and Urine Markers of Single Ascending Dose of GSK4771261 in Healthy Participants and Participants With Autosomal Dominant Polycystic Kidney Disease

Phase 1

Recruiting

• Conditions: Kidney Disease
• Interventions: Drug: GSK4771261; Drug: Placebo matching GSK4771261

• Registration Number: NCT06734234
• Lead Sponsor: GlaxoSmithKline

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2024-12-11
• Study First Submitted: 2024-12-11
• Study First Submitted QC: 2024-12-11
• Study First Posted: 2024-12-16
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-25
• Primary Completion: 2026-07-16
• Study Completion: 2026-08-13

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

For Part A

• 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.
• 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:

• Body weight >=45 kg and BMI within the range 19.5 to 32 kg/m^2, inclusive.
• Capable of giving signed informed consent, Confirmed diagnosis of 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.
• 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 milliliters 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 hours 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 milliliters 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.
• QT interval corrected (QTc)>450 milliseconds (msec). 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 hematological disorder (affecting hemoglobin, 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 United Kingdom (UK) units of alcohol. One UK unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 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 <=3.0xULN as long as direct bilirubin is <=1.0xULN.
• 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.

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 millimeters 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 >= 160 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. Paracetamol, at doses of <= 4 gram per 24 hour (g/24 hour) 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 symptomatic kidney cyst hemorrhage or infection within 12 weeks prior to screening.
• Evidence of current, chronic, or recurrent kidney or liver cyst infection.
• Estimated proteinuria >1g/24 hour 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.
• 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).
• 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 HIV antibody test.
• Evidence of SARS-CoV-2 infection, as determined by local diagnostic procedures.
• Evidence at screening of clinically significant hematological disorder (affecting hemoglobin, RBC, 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 (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 (approximately240 mL) of beer, 1 glass (125 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 <=3.0xULN as long as direct bilirubin is <=1.0xULN.
• 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 HBsAg and/or (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 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: Cohort 6: Participants receiving GSK4771261 Dose level 6	GSK4771261	Healthy participants will be randomized to receive GSK4771261 Dose level 6.
Part A: Cohort 7 (optional): Participants receiving GSK4771261 Dose level 7	GSK4771261	Healthy participants will be randomized to receive GSK4771261 Dose level 7 as the recommendation of Dose escalation committee (DEC).
Part A: Cohort 8 (optional): Participants receiving GSK4771261 Dose level 8	GSK4771261	Healthy participants will be randomized to receive GSK4771261 Dose level 8, as per the recommendation from DEC.
Part B: Cohort 4 (optional): Participants receiving GSK4771261 Dose level 12	GSK4771261	Participant with ADPKD will be randomized to receive GSK4771261 Dose level 12 as the recommendation from DEC.
Part B: Cohort 2: Participants receiving GSK4771261 Dose level 10	GSK4771261	Participant with ADPKD will be randomized to receive GSK4771261 Dose level 10.
Part B: Cohort 3: Participants receiving GSK4771261 Dose level 11	GSK4771261	Participant with ADPKD will be randomized to receive GSK4771261 Dose level 11.
Part B: Cohort 5 (optional): Participants receiving GSK4771261 Dose level 13	GSK4771261	Participant with ADPKD will be randomized to receive GSK4771261 Dose level 13, as per the recommendation from DEC.
Part A: Cohort 1: Participants receiving GSK4771261 Dose level 1	GSK4771261	Healthy participants will be randomized to receive GSK4771261 Dose level 1.
Part A: Cohort 2 : Participants receiving GSK4771261 Dose level 2	GSK4771261	Healthy participants will be randomized to receive GSK4771261 Dose level 2.
Part A: Cohort 3: Participants receiving GSK4771261 Dose level 3	GSK4771261	Healthy participants will be randomized to receive GSK4771261 Dose level 3.
Part A: Cohort 4: Participants receiving GSK4771261 Dose level 4	GSK4771261	Healthy participants will be randomized to receive GSK4771261 Dose level 4.
Part A: Cohort 5: Participants receiving GSK4771261 Dose level 5	GSK4771261	Healthy participants will be randomized to receive GSK4771261 Dose level 5.
Part B: Cohort 1: Participants receiving GSK4771261 Dose level 9	GSK4771261	Participant with Autosomal dominant polycystic kidney disease (ADPKD) will be randomized to receive GSK4771261 Dose level 9.
Part A: Participants receiving placebo matching GSK4771261	Placebo matching GSK4771261	Participants will receive placebo matching GSK4771261
Part B: Participants receiving placebo matching GSK4771261	Placebo matching GSK4771261	Participants will receive placebo matching GSK4771261

Primary Outcome Measures

Name	Time	Method
Part B: Number of Participants with Clinically Significant Changes in Vital Signs	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with clinically significant changes in vital signs will be evaluated.
Part A: Number of Participants with Adverse events (AEs)	From Baseline (Day 1) up to Day 183 (End of study [EoS])	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.
Part B: Number of Participants with Adverse events (AEs)	From Baseline (Day 1) up to Day 183 (EoS)	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.
Part A: Number of Participants with Serious Adverse Events (SAEs)	From Baseline (Day 1) up to Day 183 (EoS)	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.
Part B: Number of Participants with Serious Adverse Events (SAEs)	From Baseline (Day 1) up to Day 183 (EoS)	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.
Part A: Number of Participants with Clinically Significant Changes in Blood Laboratory Values	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with clinically significant changes in blood laboratory values will be evaluated.
Part B: Number of Participants with Clinically Significant Changes in Blood Laboratory Values	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with clinically significant changes in blood laboratory values will be evaluated.
Part A: Number of Participants with Clinically Significant Changes in Urine Laboratory Values	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with clinically significant changes in Urine laboratory values will be evaluated.
Part B: Number of Participants with Clinically Significant Changes in Urine Laboratory Values	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with clinically significant changes in Urine laboratory values will be evaluated.
Part A: Number of Participants with Clinically Significant Changes in Vital Signs	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with clinically significant changes in vital signs will be evaluated.
Part A: Number of Participants with Clinically Significant Changes in 12-lead Electrocardiogram (ECG)	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with clinically significant changes in 12-lead ECG parameters will be evaluated.
Part B: Number of Participants with Clinically Significant Changes in 12-lead ECG	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with clinically significant changes in 12-lead ECG parameters will be evaluated.

Secondary Outcome Measures

Name	Time	Method
Part A: Number of Participants with Anti-drug Antibodies for GSK4771261	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with Anti-drug antibodies for GSK4771261 will be evaluated.
Part B: Number of Participants with Anti-drug Antibodies for GSK4771261	From Baseline (Day 1) up to Day 183 (EoS)	Number of participants with Anti-drug antibodies for GSK4771261 will be evaluated.
Part A: Area under the concentration-time curve to the end of the dosing period AUC (0-tau)of GSK4771261	Up to Day 182	Blood samples were collected to evaluate pharmacokinetics of GSK4771261.
Part A: Area under the concentration-time curve to infinity AUC (0-inf) of GSK4771261	Up to Day 182	Blood samples were collected to evaluate pharmacokinetics of GSK4771261.
Part B: AUC (0-tau) of GSK4771261	Up to Day 182	Blood samples were collected to evaluate pharmacokinetics of GSK4771261.
Part B: AUC (0-inf) of GSK4771261	Up to Day 182	Blood samples were collected to evaluate pharmacokinetics of GSK4771261.
Part A: Maximum Plasma Concentration (Cmax) of GSK4771261	Up to Day 182	Blood samples were collected to evaluate pharmacokinetics of GSK4771261.
Part B: Cmax of GSK4771261	Up to Day 182	Blood samples were collected to evaluate pharmacokinetics of GSK4771261.

Trial Locations

Locations (1)

GSK Investigational Site; 🇬🇧 Cambridge, United Kingdom