Chronic Kidney Disease
Conditions
Brief summary
The ARTIST-CKD trial is a clinical study evaluating the effect of weekly subcutaneous administration of survodutide (3.6 mg) on kidney function in patients with chronic kidney disease (CKD) and elevated albuminuria. The primary objective is to determine whether survodutide leads to early, sustained, and clinically meaningful reductions in albuminuria, regardless of diabetes status.
Interventions
DRUGSurvodutide (BI 456906)
0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg, 3.6 mg s.c. weekly
DRUGPlacebo
Placebo matching survodutide
Sponsors
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a parallel, randomized, double-blind, placebo-controlled clinical trial conducted in 4 countries (Netherlands, Germany, Spain and Australia)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * eGFR ≥20 and \<90 mL/min/1.73m2 * Urinary albumin to creatinine ratio \>30 mg/g and \<3500 mg/g * BMI \>21 kg/m2 * Stable kidney function (no more than 30% change in eGFR in the 3 months prior to enrolment) * On a stable maximum tolerated dose of an ACEi/ARB for at least 4 weeks prior to enrolment * If using an SGLT2 inhibitor, receiving a stable dose for at least 8 weeks prior to enrolment * Willing to sign an informed consent
Exclusion criteria
* Diagnosis of type 1 diabetes * Cardiovascular event within 3 months prior to enrolment * Treatment with GLP-1RA for \<12 weeks prior to screening * Evidence of severe hepatic impairment determined by any one of: ALT or AST values exceeding 3x ULN, a history of hepatic encephalopathy, a history of oesophageal varices, or a history of portocaval shunt; * Active pregnancy or breastfeeding * History of kidney or liver transplant * Active malignancy * Suggestive evidence of adrenal insufficiency * Acute pancreatitis \<180 days prior to screening * History of chronic pancreatitis or idiopathic acute pancreatitisPersonal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma * Calcitonin levels ≥100 pg/mL or 29.26 pmol/L * Personal history of non-familial medullary thyroid carcinoma * History of severe hypersensitivity or contraindications to any glucagon RA or GLP-1 RA * Uncontrolled arterial hypertension (mean semi supine systolic blood pressure (SBP) ≥180 mmHg or diastolic blood pressure (DBP) ≥110 mmHg) * Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: * History of active inflammatory bowel disease within the 6 months; * Major gastrointestinal tract surgery as determined by the physician; * Pancreatitis within 6 months. * GI ulcers and/or bleeding within 6 months; * Evidence of urinary obstruction or difficulty in voiding at screening. * Participation in any clinical trial within 3 months prior to initial dosing. * Donation or loss of ≧400 ml blood within 8 weeks prior to initial dosing. * History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening or according to investigator's assessment. * History of noncompliance to medical regimens or unwillingness to comply with the study protocol. * Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study. * Women of childbearing potential (WOCBP): * WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug in such a manner the risk of pregnancy is minimized. * WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent of HCG) at screening. * Vulnerable (i.e. under guardianship) or mentally incapacitated subjects (i.e. not able to understand and sign the informed consent)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in first morning void UACR | From baseline to week 32/36 | Average of first morning void urine samples collected at week 32 and 36 will be used to decrease random day-to-day variability and increase precision (and statistical power). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UACR and eGFR during 4-week wash-out | From week 36 to 40 | — |
| Subcutaneous and visceral fat assessed by MRI | From baseline to week 36 | Same subset of 60 participants with Iohexol GFR |
| Body weight | From baseline to week 36 | — |
| Waist circumference | From baseline to week 36 | — |
| Systolic and diastolic blood pressure | From baseline to week 36 | — |
| eGFR (creatinine, cystatin C, and creatinine-cystatin C) | From baseline to week 36 | — |
| Iohexol measured GFR | From baseline to week 36 | Subset of 60 participants |
| Perirenal and renal sinus fat measured by MRI | From baseline to week 36 | Same subset of 60 participants with Iohexol GFR |
Other
| Measure | Time frame | Description |
|---|---|---|
| NT-proBNP | From baseline to week 36 | — |
| Renal blood flow measured by MRI | From baseline to week 36 | Same subset of 60 participants with Iohexol GFR |
| HbA1c | From baseline to week 36 | — |
| High-sensitivity C-reactive protein | From baseline to week 36 | — |
Contacts
Primary ContactHiddo J Lambers Heerspink, Prof. Dr.
Outcome results
None listed