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

Running, not enrolling · Phase 1 · Has a placebo group

Conditions studied: Kidney Disease

In brief

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).

Key facts

Study ID

NCT06734234

Run by

GlaxoSmithKline

People needed

86

Starts

2024-12-11

Expected to finish

2027-07-23

Last updated by the study team

2026-07-30

Who can join

Age: 25 and older, up to 65. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• 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 (planned Cohorts 1-3 and optional cohorts 4-5):
• 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 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
• 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 and/or existing genetic information collected during the participant's routine clinical care for ADPKD from a genetic testing provider that, in the judgement of the investigator, is clinically valid.
• Mayo imaging classification groups 1C, 1D or 1E as assessed using the information collected at screening
• Estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 45 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 For Part B (additional inclusion criteria for optional cohorts 4-5 only)
• eGFR >=30 mL/min/1.73m\^2 (based on the CKD-EPI 2021 eGFR equation) and, in the clinical judgement of the investigator, the participant:
• has been clinically stable for the 24 months before screening; and,
• is not anticipated by the participant's regular treating physician to have a sustained decline in kidney function by >10% over the following 12 months; and,
• is not anticipated to need renal replacement therapy in the next 12 months; and,
• does not have any other clinical, biochemical or familial feature at screening that suggests a clinically significant decline in kidney function is anticipated in the next 12 months.

You may not qualify if…

• 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.)

Where it is running

• GSK Investigational Site — Rochester, Minnesota, United States
• GSK Investigational Site — Brussels, Belgium
• GSK Investigational Site — Ghent, Belgium
• GSK Investigational Site — Leuven, Belgium
• GSK Investigational Site — London, Ontario, Canada
• GSK Investigational Site — Toronto, Ontario, Canada
• GSK Investigational Site — Montreal, Quebec, Canada
• GSK Investigational Site — Brest, France
• GSK Investigational Site — Paris, France
• GSK Investigational Site — Cologne, North Rhine-Westphalia, Germany
• GSK Investigational Site — Lübeck, Schleswig-Holstein, Germany
• GSK Investigational Site — Groningen, Netherlands
• GSK Investigational Site — Leiden, Netherlands
• GSK Investigational Site — Rotterdam, Netherlands
• GSK Investigational Site — Barcelona, Spain
• GSK Investigational Site — Barcelona, Spain
• GSK Investigational Site — Barcelona, Spain
• GSK Investigational Site — Madrid, Spain
• GSK Investigational Site — Madrid, Spain
• GSK Investigational Site — Cambridge, United Kingdom
• GSK Investigational Site — Exeter, United Kingdom
• GSK Investigational Site — London, United Kingdom
• GSK Investigational Site — Newcastle upon Tyne, United Kingdom

Full record on ClinicalTrials.gov

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