A Research Study Comparing How Well Different Doses of the Medicine NNC0519-0130 Can Reduce Kidney Damage in People Living With Chronic Kidney Disease

Official title

Efficacy, Safety and Pharmacokinetics of NNC0519-0130 Once Weekly s.c. Versussemaglutide 1.0 mg and Placebo in People With Chronic Kidney Disease, With or Without Type 2 Diabetes, and With Overweight or Obesity: a Proof-of-concept and Dose-finding Study

Overview

The study evaluates the safety of different doses of a new medicine called NNC0519 0130. It also looks into how the medicine may improve kidney function in participants with chronic kidney disease with or without type 2 diabetes, living with overweight or obesity. The participants will either get NNC0519-0130 (a new medicine), semaglutide (a medicine that doctors can already prescribe), or placebo (a "dummy" substance). Which treatment the participant will get is decided by chance. The study will last for up to 43 weeks.

Interventions

• Drug NNC0519-0130
  NNC0519-0130 will be administered subcutaneously.
• Drug Placebo
  Placebo matching NNC0519-0130 will be administered subcutaneously.
• Drug Semaglutide
  Semaglutide will be administered subcutaneously.

Primary outcome measures

• Change in urinary albumin-to-creatinine ratio (UACR) at week 12 [Time frame: From baseline (week 0) to end of a given maintenance dose period (week 12)]
• Change in urinary albumin-to-creatinine ratio (UACR) at week 24 [Time frame: From baseline (week 0) to end of a given maintenance dose period (week 24)]
• Change in urinary albumin-to-creatinine ratio (UACR) at week 36 [Time frame: From baseline (week 0) to end of a given maintenance dose period (week 36)]

Secondary outcome measures (10)

• Change in estimated glomerular filtration rate (eGFR) (creatinine and cystatin C-based Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021) [Time frame: From baseline (week 0) to end of treatment (week 36)]
• Change in estimated glomerular filtration rate (eGFR) (creatinine-based CKD-EPI 2021) [Time frame: From baseline (week 0) to end of treatment (week 36)]
• Relative change in body weight [Time frame: From baseline (week 0) to end of treatment (week 36)]
• Achievement of greater than or equal to (≥) 5 percentage (%) weight reduction [Time frame: From baseline (week 0) to end of treatment (week 36)]
• Achievement of greater than or equal to (≥) 10 percentage (%) weight reduction [Time frame: From baseline (week 0) to end of treatment (week 36)]
• Change in waist circumference [Time frame: From baseline (week 0) to end of treatment (week 36)]
• Change in glycated haemoglobin (HbA1c) [Time frame: From baseline (week 0) to end of a given maintenance dose period (week 12, 24 or 36)]
• Change in systolic blood pressure [Time frame: From baseline (week 0) to end of treatment (week 36)]
• Change in diastolic blood pressure [Time frame: From baseline (week 0) to end of treatment (week 36)]
• Number of treatment emergent adverse events (TEAEs) [Time frame: From baseline (week 0) to end of study (week 40)]

Eligibility criteria

Inclusion criteria

• Female of non-childbearing potential, or male.

• For US only: Female of childbearing potential using highly effective non-systemic methods of contraception with low user-dependency at least 2 months prior to screening and willingness to continue using it through-out the study, or male.
• Age 18 years or above at the time of signing the informed consent.
• Diagnosed with type 2 diabetes mellitus greater than or equal to (≥) 180 days before screening, or not diagnosed with type 2 diabetes mellitus.

• HbA1c of 6.5 percentage (%)-10.5 percentage (%) \[48 - 91 millimoles per mole (mmol/mol)\] (both inclusive) if diagnosed with type 2 diabetes mellitus, or HbA1c of less than (<)6.5 percentage (%) \[<48 mmol/mol\] if not diagnosed with type 2 diabetes mellitus.
• BMI greater than or equal to (≥) 27.0 kilogram per square metre (kg/m\^2) at screening.
• Kidney impairment defined by serum creatinine and cystatin C-based Egfr greater than or equal to (≥) 15 and less than (<) 90 mL/min/1.73 m\^2.
• Albuminuria defined by Urine Albumin-to-Creatinine Ratio (UACR) greater than or equal (≥)100 and less than (<) 5000 milligram per gram (mg/g).
• Treatment with maximum labelled or tolerated dose of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated, in the opinion of the investigator. Treatment dose must be stable for at least 30 days prior to screening.

Exclusion criteria

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective non-systemic contraception with low user-dependency.
• Lupus nephritis or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
• Receiving immunosuppressive therapy for primary or secondary renal disease within 6 months prior to screening.
• Use of any glucagon-like peptide-1 (GLP-1) RA (including medication with GLP-1 RA activity, e.g., GIP/GLP-1 RA) within 90 days prior to screening.
• Myocardial infarction, stroke, transient ischaemic attack, or hospitalization for unstable angina pectoris within 180 days before screening.
• Chronic or intermittent haemodialysis or peritoneal dialysis within 90 days before screening.
• Only applicable for participants with type 2 diabetes (T2D): Uncontrolled and potentially unstable diabetic retinopathy or diabetic maculopathy. Verified by an eye examination performed within 90 days before 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.
• Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low-risk prostate cancer, or in-situ carcinomas of the cervix or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN)) within 5 years before screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Japan · 19 centers

• Seino Internal Medicine Clinic_Internal medicine — Koriyama-shi, Fukushima
• TOSAKI Clinic for Diabetes and Endocrinology_Diabetes and Endocrinology — Aichi
• Naka Kinen Clinic_Internal medicine — Ibaraki
• Naka Kinen Clinic_Internal medicine — Ibaraki
• Fujisawa City Hospital_Kidney internal medicine — Kanagawa
• Fujisawa City Hospital_Kidney internal medicine — Kanagawa
• Higashijujo Sakai Diabetes Clinic_Internal Medicine — Kita-ku, Tokyo
• Koshigaya Municipal Hospital_Internal medicine — Saitama
• … and 11 more centers

Poland · 19 centers

Center list to be confirmed — check the primary protocol.

United States · 18 centers

• N America Res Inst - San Dimas — San Dimas
• NorCal Endocrinology and Internal Medicine — San Ramon
• Rocky Mount Reg VA Med-DN — Aurora
• Northeast Research Institute — Fleming Island
• Encore Medical Research LLC — Hollywood
• Northeast Research Institute — Saint Augustine
• Clinical Research of Cent FL — Winter Haven
• Endeavor Health — Skokie
• … and 10 more centers

Turkey (Türkiye) · 14 centers

Center list to be confirmed — check the primary protocol.

Spain · 13 centers

Center list to be confirmed — check the primary protocol.

Malaysia · 10 centers

Center list to be confirmed — check the primary protocol.

Bulgaria · 9 centers

• SRH - Zdrave EAD — Bankya
• Medical centre Zdrave 1 OOD — Kozloduy
• Nader Yabrudi - ASMPVBE Individual practice — Smolyan
• Medical Centre Acad. Iv. Penchev EOOD — Sofia
• Medical Centre Acad. Iv. Penchev EOOD — Sofia
• USHATE Akad. Ivan Penchev EAD, Second Clinic of Endocrinology — Sofia
• UMHAT Sofiamed EAD — Sofia
• UMHAT Sveta Anna Sofia AD, Second Clinic of Internal Diseases — Sofia
• … and 1 more center

Czechia · 8 centers

• Nemocnice Český Krumlov, a.s. — Český Krumlov
• MUDr. Petr Buček s.r.o. — Frýdek-Místek
• CTC Hodonin s.r.o. — Hodonín
• FNKV-Internal Clinic-Nephrology — Prague
• DiaVize s.r.o. — Prague
• IKEM Klinika nefrologie — Prague
• Fledip s.r.o. — Prague
• Internist Care s.r.o. — Smiřice

Italy · 8 centers

• ASL Avezzano Sulmona L'Aquila - Ospedale San Salvatore - UOC Diabetologia — L’Aquila
• Università degli studi G. D'Annunzio Chieti Pescara - CAST — Chieti
• A.O.U. Bologna_ Policlinico S.Orsola Malpighi — Bologna
• Azienda Ospedaliera Papa Giovanni XXIII — Bergamo
• Azienda Ospedaliera Spedali Civili di Brescia — Brescia
• Azienda Ospedaliera Luigi Sacco — Milan
• Azienda Ospedaliero Universitaria Pisana Ospedale Cisanello — Pisa
• Fondazione Policlinico Universitario Agostino Gemelli IRCS — Roma

India · 7 centers

• Endolife Specialty Hospitals — Guntur
• MS Ramaiah — Bengaluru
• Government Medical College, Kozhikode — Kozhikode
• SMS Medical College & Hospital — Jaipur
• Diabetes, Thyroid and Endocrine Centre — Jaipur
• Diabetes Research Center, Hyderabad — Hyderabad
• Nizams Institute of Medical Science — Hyderabad

Brazil · 6 centers

• Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV — Curitiba
• Instituto Pró-Renal Brasil — Curitiba
• Centro de Diabetes Curitiba — Curitiba
• Irmandade da Santa Casa de Misericórdia de Porto Alegre — Porto Alegre
• Núcleo de Pesquisa Clínica do Rio Grande do Sul Ltda. — Porto Alegre
• Hospital do Rim e Hipertensao Fundacao Oswaldo Ramos — São Paulo

South Korea · 6 centers

Center list to be confirmed — check the primary protocol.

Argentina · 5 centers

• Centro Médico CIMEL — Lanús Este
• Renalida — Mar del Plata
• Centro de Investigaciones Metabólicas — City of Buenos Aires
• Instituto de Cardiología de Corrientes — Corrientes
• Instituto de Investigaciones Clinicas Mar Del Plata — Mar del Plata

Australia · 5 centers

• Castle Hill Medical Centre — Castle Hill
• Gosford Renal Research — Gosford
• Heart of Australia — Chelmer
• Melbourne Renal Research Group — Reservoir
• Sunshine Hospital - Western Centre for Health Research and Education — St Albans

Identifiers

NCT: NCT06717698 · NN9541-7841 · U1111-1302-5591 · 2024-510846-15

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗