Effect of Survodutide on Albuminuria in Patients with Chronic Kidney Disease
- Trial ID
- 2025-525068-13-00
- Protocol
- 22774
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the efficacy of survodutide 3.6 mg per week on albuminuria in patients with chronic kidney disease, regardless of diabetic status. Secondary objectives include the assessment of estimated glomerular filtration rate (eGFR) using creatinine, cystatin C, and creatinine-cystatin C, as well as evaluating the glomerular filtration rate (GFR) measured via iohexol in a specific subset. Additionally, the study investigates changes in the urinary albumin-to-creatinine ratio (UACR) and eGFR during a 4-week wash-out period. Further evaluations involve magnetic resonance imaging (MRI) to assess perirenal fat, renal sinus fat, subcutaneous fat, and visceral fat. Other secondary outcomes include changes in body weight, waist circumference, and blood pressure.
Participants
The study involves 25 participants diagnosed with chronic kidney disease. The population includes both male and female individuals within the age ranges corresponding to codes 3 and 4. Eligible participants must have an estimated glomerular filtration rate between 20 and 90 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio between 30 and 3500 mg/g. Inclusion requires a body mass index of at least 23 kg/m2, with a restriction that individuals possessing a BMI between 23 and 25 kg/m2 represent no more than 10% of the total cohort. Participants must exhibit stable kidney function and maintain a stable maximum tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker for at least 4 weeks. Furthermore, those utilizing a sodium-glucose cotransporter-2 inhibitor or a mineralocorticoid receptor antagonist must have received a stable dose for at least 8 weeks prior to enrolment.
Plans and Procedures
This Phase II clinical trial is designed to evaluate the effects of survodutide on albuminuria in individuals with chronic kidney disease, regardless of diabetic status. The study utilizes a randomized approach to compare different doses of the test substance, including 0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg, and 3.6 mg administered via subcutaneous injection, against a matching placebo. The primary endpoint is the percentage change from baseline to week 32 or 36 in the first morning void urinary albumin to creatinine ratio. Secondary outcomes include changes in estimated glomerular filtration rate, body weight, and blood pressure. The study sequence involves a screening visit to assess eligibility based on criteria such as age, body mass index, and stable kidney function. Following enrollment, participants undergo a treatment period through week 36, followed by a 4-week wash-out period between week 36 and week 40 to monitor changes in kidney function. The estimated duration of the trial, from recruitment to completion, is approximately 21 months.
Treatment
The experimental medication is survodutide (also identified as BI 456906), which is supplied as a solution for injection. The administration is performed via subcutaneous injection at various dosage levels, including 0.3 mg, 0.6 mg, 1.2 mg, and 3.6 mg. An additional dosage of 2.4 mg is also specified for the investigative substance.
The control group receives a matching placebo for survodutide.
Efficacy
The efficacy of survodutide in patients with chronic kidney disease is assessed through several parameters. The primary endpoint is the percentage change from baseline to week 32/36 in the first morning void urinary albumin-to-creatinine ratio (UACR).
Secondary endpoints include the following evaluations from baseline to week 36:
- Change in estimated glomerular filtration rate (eGFR) using creatinine, cystatin C, and creatinine-cystatin C.
- Change in Iohexol measured GFR in a subset of 60 participants.
- Change in perirenal and renal sinus fat measured by magnetic resonance imaging (MRI) in a subset of 60 participants.
- Change in subcutaneous and visceral fat assessed by MRI in a subset of 60 participants.
- Change in body weight.
- Change in waist circumference.
- Change in systolic and diastolic blood pressure.
Additionally, changes in UACR and eGFR are measured during a 4-week wash-out period from week 36 to week 40.
Inclusion and Exclusion Criteria
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 ≥ 23 kg/m2 (with participants with BMI ≥23 to <25 capped at 10% of the total study population)
- 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
- If using an MRA, receiving a stable dose for at least 8 weeks prior to enrolment
Exclusion Criteria
- Diagnosis of type 1 diabetes
- 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
- A history of acute pancreatitis
- 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; A history of pancreatitis; 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 chronic pancreatitis or idiopathic acute pancreatitis
- 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 without 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)
- Personal 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)
- Cardiovascular event within 3 months prior to enrolment
- Treatment with GLP-1RA for <12 weeks prior to screening
- Use of sensitive CYP3A4 substrates with a narrow therapeutic index (e.g. alfentanil, fentanyl, carbamazepine, cyclosporine, tacrolimus, sirolimus) or use of any GLP-1, GIP/GLP-1 or GIP/GLP-1/glucagon receptor agonist
- Elevation of serum lipase (>3 x ULN)
- HbA1c > 10.5%
- Uncontrolled unstable diabetic retinopathy or maculopathy
- Additional criteria applicable for sub-set of participants for MRI assessment of perirenal, epicardial, subcutaneous and visceral fat: o Contraindication to MRI including, but not limited to severe claustrophobia, extensive tattoos, inner ear implant, pacemakers incompatible with MRI, other implanted cardiac rhythm management device, intracranial aneurism clips incompatible with MRI, any other metallic, non-MRI compatible implanted devices (e.g. hip replacement), a history of intra-orbital metal fragments that have not been removed, and weight or girth that exceeds scanner capabilities o Participants who do not fulfil the MRI criteria are eligible for the main trial if the eligibility criteria for the main trial are fulfilled.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Yet Recruiting | 01 Apr 2026 | 17 |
 The Netherlands | Not Yet Recruiting | 01 Apr 2026 | — |
 Spain | Not Yet Recruiting | 01 Apr 2026 | 45 |
| Netherlands | — | — | 33 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Matching placebo for Survodutide | Placebo | N/A | — | — | — | N/A |
BI 456906 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 0.6 | 32 | PRD10189602 |
BI 456906 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 3.6 | 20 | PRD10189614 |
BI 456906 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 1.2 | 28 | PRD10189603 |
BI 456906 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 0.3 | 36 | PRD10189601 |
BI 456906 | Test | SOLUTION FOR INJECTION | SOLUTION FOR INJECTION | 2.4 | 24 | PRD10189613 |