CAGRILINTIDE, SEMAGLUTIDE for Type 2 diabetes | Painful diabetic peripheral neuropathy

Inclusion criteria

• {"criterion_text":"- Male or female."}
• {"criterion_text":"- Age 18 years or above at the time of signing the informed consent."}
• {"criterion_text":"- Body mass index (BMI) ≥25.0 kg/m2 at screening."}
• {"criterion_text":"- Diagnosis of type 2 diabetes (T2D) ≥180 days before screening. For participants on anti-diabetic drugs: Stable daily and/or weekly dose(s) ≥90 days before screening of any of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose, as judged by the investigator: Treatment with 1-3 marketed oral antidiabetic drugs (OADs) (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2 inhibitors (SGLT2i), thiazolidinediones, or sulphonylureas (SU) as a single agent or in combination) according to local guidelines. Treatment with basal or basal-bolus insulin (including premixed insulin formulations) according to local guidelines."}
• {"criterion_text":"- HbA1c ≤10.5 % (91 mmol/mol) and ≥6.0 % (42 mmol/mol), as determined by central laboratory at screening."}
• {"criterion_text":"- Diagnosis of painful diabetic peripheral neuropathy (pDPN) at screening as well as the following criteria: Participant with self-reported pain consistent with pDPN for a minimum of 3 months before screening, as judged by the investigator. AND CCI at screening. AND CCI at screening."}
• {"criterion_text":"- The weekly CCI must meet the following criteria in both weeks during the screening period (day -14 to -8 and day -7 to -1): Completion of daily CCI reporting in the eDiary for a minimum of 4 out of 7 days each week. AND The weekly CCI. AND The CCI."}
• {"criterion_text":"- Stable pharmacological and non-pharmacological treatment of pain for a minimum of 3 months before screening, in the opinion of the investigator. The treatment regimen should adhere to local guidelines (if available)."}

Exclusion criteria

• {"criterion_text":"- Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method."}
• {"criterion_text":"- Any other painful medical condition(s) where the pain is significantly more severe than the diabetic peripheral neuropathy pain, as judged by the investigator (participants will not be excluded if the pain is transient in nature)."}
• {"criterion_text":"- History of suicidal attempt within 5 years before screening."}
• {"criterion_text":"- Suicidal behaviour within 1 month before screening."}
• {"criterion_text":"- Renal impairment with estimated Glomerular Filtration Rate (eGFR) <30 ml/min/1.73 m2 as determined by central laboratory at screening."}
• {"criterion_text":"- Exposure to an investigational medicinal product within 90 days or 5 half-lives of the investigational medicinal product (if known), whichever is longer, before screening."}
• {"criterion_text":"- Use of any glucagon-like peptide-1 receptor agonist (GLP1 RA), including medication with GLP1 RA activity (DPP-4), or amylin analogue within 60 days before screening."}
• {"criterion_text":"- Significant use of opioids, cannabinoids or benzodiazepines within 30 days before screening, in the opinion of the investigator. Significant use is defined as use that renders it unlikely that the participant is able to comply with protocol requirements for discouraged medications."}
• {"criterion_text":"- Anticipated initiation or clinically relevant change in concomitant medications (for more than 14 consecutive days during the study) known to affect weight or glucose metabolism (e.g., orlistat, thyroid hormones or oral systemic corticosteroids)."}
• {"criterion_text":"- Planned initiation or change in antidepressant, antipsychotic or antiepileptic medication. If participants are already taking such medication, they should have stable and optimised treatment for at least 8 weeks before screening."}
• {"criterion_text":"- Presence or history of epilepsy."}
• {"criterion_text":"- Presence or history of fibromyalgia."}
• {"criterion_text":"- Presence of non-diabetic neuropathies, in the opinion of the investigator."}
• {"criterion_text":"- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination and OCT assessment 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."}

Primary endpoints

• {"endpoint_text":"- Change in weekly average Pain Intensity-Numerical Rating Scale (PI-NRS)","definition_or_measurement_approach":"Change measured as the difference in the weekly average PI-NRS score from baseline (weekly average Pain Intensity on the Numerical Rating Scale)."}

Secondary endpoints

• {"endpoint_text":"- Participants reaching ≥30 % reduction in PI-NRS Pain (yes/no)","definition_or_measurement_approach":"Binary outcome indicating whether participant achieves ≥30% reduction in PI-NRS compared to baseline."}
• {"endpoint_text":"- Time to achieve ≥30% reduction in weekly average PI-NRS Pain","definition_or_measurement_approach":"Time-to-event measurement (time from baseline to first occurrence of ≥30% reduction in weekly average PI-NRS)."}
• {"endpoint_text":"- Participants reaching ≥50 % reduction in PI-NRS Pain (yes/no)","definition_or_measurement_approach":"Binary outcome indicating whether participant achieves ≥50% reduction in PI-NRS compared to baseline."}
• {"endpoint_text":"- Time to achieve ≥50% reduction in weekly average PI-NRS Pain","definition_or_measurement_approach":"Time-to-event measurement (time from baseline to first occurrence of ≥50% reduction in weekly average PI-NRS)."}
• {"endpoint_text":"- Change in Brief Pain Inventory-Short Form (BPI-SF)","definition_or_measurement_approach":"Change from baseline in BPI-SF scores."}
• {"endpoint_text":"- Change in Chronic Pain Sleep Inventory 3-item (CPSI 3)","definition_or_measurement_approach":"Change from baseline in CPSI 3 scores."}
• {"endpoint_text":"- Change in Michigan Neuropathy Screening Instrument (MNSI)","definition_or_measurement_approach":"Change from baseline in MNSI scores."}
• {"endpoint_text":"- Change in systolic blood pressure","definition_or_measurement_approach":"Change from baseline in systolic blood pressure (mmHg)."}
• {"endpoint_text":"- Change in diastolic blood pressure","definition_or_measurement_approach":"Change from baseline in diastolic blood pressure (mmHg)."}
• {"endpoint_text":"- Change in glycated haemoglobin (HbA1c)","definition_or_measurement_approach":"Change from baseline in HbA1c measured by central laboratory."}
• {"endpoint_text":"- Change in Fasting Plasma Glucose (FPG)","definition_or_measurement_approach":"Change from baseline in fasting plasma glucose measured by central laboratory."}
• {"endpoint_text":"- Relative change in body weight","definition_or_measurement_approach":"Relative (%) change from baseline in body weight."}
• {"endpoint_text":"- Change in waist circumference","definition_or_measurement_approach":"Change from baseline in waist circumference (cm)."}
• {"endpoint_text":"- Ratio to baseline in: Total cholesterol, High-density lipoprotein (HDL) cholesterol, Low-density lipoprotein (LDL) cholesterol, Very low-density lipoprotein (VLDL) cholesterol, Triglycerides, Free fatty acids, Non-HDL cholesterol","definition_or_measurement_approach":"Ratio of follow-up value to baseline for listed lipid and lipid-related biomarkers measured in central laboratory."}
• {"endpoint_text":"- Relative change in high-sensitivity C-reactive protein (hsCRP)","definition_or_measurement_approach":"Relative (%) change from baseline in hsCRP measured in central laboratory."}
• {"endpoint_text":"- Number of treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Count of TEAEs during treatment period."}
• {"endpoint_text":"- Number of treatment-emergent serious adverse events (TESAEs)","definition_or_measurement_approach":"Count of TESAEs during treatment period."}
• {"endpoint_text":"- Number of severe hypoglycaemic episodes (level 3)","definition_or_measurement_approach":"Count of level 3 severe hypoglycaemic events."}
• {"endpoint_text":"- Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter))","definition_or_measurement_approach":"Count of level 2 hypoglycaemic episodes (<3.0 mmol/L confirmed by blood glucose meter)."}

Methods

• Recruitment via recruitment advertisement posters (country-specific K2 recruitment advertisement posters) — posters titled e.g., 'Recruitment Advertisement poster-Pain', 'Recruitment Advertisement poster-Contribute to research', 'Easy to participate' (documents present for Norway, Spain, France, Denmark).
• Recruitment via recruitment leaflets (country-specific recruitment leaflets) distributed at participating hospital/clinic sites (documents exist for Norway, Spain, France, Denmark).
• Site-based recruitment through participating hospitals and clinics (site lists provided per country).
• Country-specific digital/material recruitment content (document titled 'trialtree-dk' and other country-specific recruitment advertisement material for Denmark suggests use of digital/organized recruitment materials).

Norway

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

08-04-2026

Processing Time Days

506

Number Of Sites

4

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

532

Number Of Sites

7

Number Of Participants

26

Denmark

Earliest CTIS Part Ii Submission Date

11-11-2024

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

506

Number Of Sites

4

Number Of Participants

14

France

Earliest CTIS Part Ii Submission Date

30-10-2024

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

518

Number Of Sites

5

Number Of Participants

7

Primary sponsor

Full Name

Novo Nordisk A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

4G Clinical B.V.

Responsibilities

RTSM supplier and RTSM Helpdesk

Name

Icon Clinical Research Limited

Responsibilities

Central Laboratory

Third parties

• {"country":"Denmark","full_name":"Medicus Engineering ApS","duties_or_roles":"Vendor performing exploratory research analyses","organisation_type":"Industry"}
• {"country":"Germany","full_name":"Abbott GmbH","duties_or_roles":"BG Meter","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"RTSM supplier and RTSM Helpdesk","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Celerion Switzerland AG","duties_or_roles":"Special Laboratory: Analysis in case of systemic hypersensitivity reactions - Anti-Semaglutide binding antibodies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"eCOA (ePRO app supplier)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Central Laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Oracle Danmark ApS","duties_or_roles":"CRF Supplier and Global Safety Database supplier","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Finland","full_name":"SYRINX Bioanalytics Oy","duties_or_roles":"Special Laboratory:Analysis in case of systemic hypersensitivity reactions - Anti-Cagrilintide binding antibodies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translation","organisation_type":"Pharmaceutical company"}