A research study to find out how semaglutide works in the kidneys compared to placebo, in people with type 2 diabetes and chronic kidney disease

Phase 1

• Conditions: Diabetes Mellitus, Type 2Chronic kidney disease; MedDRA version: 21.1Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 100000004861; MedDRA version: 23.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2020-000828-19-PL
• Lead Sponsor: ovo Nordisk A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-06
• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

- Male or female, age 18 years or older at the time of signing informed consent.
- Diagnosed with T2D at least 180 days prior to the day of screening.
- Glycosylated haemoglobin (HbA1c) equal to or below 9.0% (equal to or below 75 mmol/mol).
Depending on biopsy/non-biopsy population:
-For subjects in the non-biopsy population: Serum creatinine-based eGFR = 30 and =75 mL/min/1.73 m2 (CKD-EPI).
For subjects in the biopsy sub-population: Serum creatinine-based eGFR = 40 and =75 mL/min/1.73 m2 (CKD-EPI).
- Serum creatinine-based estimated glomerular filtration rate (eGFR) equal to or above 40 and equal to or below 75 mL/min/1.73 m^2 (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)).
- Urine albumin-to-creatinine ratio (UACR) equal to or above 30 and below 5000 mg/g.
- Treatment with maximum labelled or tolerated dose of a reninangiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB)) unless such treatment is contraindicated or not tolerated. Treatment dose must be stable for at least 28 days prior to screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 63
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

Exclusion Criteria

- Use of any glucagon-like peptide 1 receptor agonist (GLP-1 RA) within 30 days prior to screening.
- A prior solid organ transplant or awaiting solid organ transplant.
- Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
- Presence or history of malignant neoplasms (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) within 5 years prior to the day of screening.
- Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations.
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
- Treatment with systemic anti-inflammatory or immunosuppressant drugs within 90 days prior to screening. Stable treatment with acetylsalicylic acid for prevention of cardiovascular events and occasional use of propionic acid derivatives drugs (e.g. ibuprofen) is allowed.
• Any contraindication for MRI according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared magnetic resonance (MR) compatible.
• Combination use of an ACE inhibitor and an ARB.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the effect of once-weekly (OW) semaglutide administered subcutaneously (under the skin, s.c.) versus placebo on renal inflammation and haemodynamics, as measured by magnetic resonance imaging (MRI) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).;Secondary Objective: To investigate the effect of OW semaglutide s.c. versus placebo on renal oxidative stress, natriuresis, albumin excretion and kidney function in subjects with T2D and CKD.;Primary end point(s): 1. Change in kidney oxygenation (cortex), blood oxygenation-level dependent magnetic resonance imaging (BOLD MRI) (R2*) <br>2. Change in kidney oxygenation (medulla), BOLD MRI (R2*) <br>3. Change in global kidney perfusion (MRI) <br>4. Change in kidney inflammation (cortex), longitudinal relaxation time (T1) mapping (MRI) <br>5. Change in kidney inflammation (medulla), T1 mapping (MRI);Timepoint(s) of evaluation of this end point: 1. - 5. From baseline (week 0) to end of treatment (week 52)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Change in gene expression assessed by single nucleus ribonucleic acid (RNA) sequencing (kidney biopsy)<br>2. Change in glomerular basement membrane width (kidney biopsy)<br>3. Change in apparent diffusion coefficient (ADC) (cortex) (MRI) <br>4. Change in ADC (medulla) (MRI) <br>5. Change in mean renal artery resistive index (RARI) (MRI) <br>6. Change in mean arterial flow (MRI) <br>7. Change in natriuresis (urinary sodium excretion) (urinalysis) <br>8. Change in albumin excretion rate (urinalysis) <br>9. Change in kidney function (creatinine clearance) (urinalysis);Timepoint(s) of evaluation of this end point: 1. - 9. From baseline (week 0) to end of treatment (week 52)