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
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
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).
Enrollment
Sex
Ages
Volunteers
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
Trial design
Primary purpose
Allocation
Interventional model
Masking
84 participants in 14 patient groups
Trial contacts and locations
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Central trial contact
EU GSK Clinical Trials Call Center; US GSK Clinical Trials Call Center
Data sourced from clinicaltrials.gov
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