A Research Study to Investigate the Effects of CagriSema Compared to Placebo in People With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy

Phase 2

Recruiting

• Conditions: Diabetes Mellitus, Type 2; Diabetic Peripheral Neuropathy
• Interventions: Drug: CagriSema (Cagrilintide B and Semaglutide I); Drug: Placebo matched to CagriSema (Cagrilintide B and Semaglutide I)

• Registration Number: NCT06797869
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This study will look at the effects of CagriSema in people with both type 2 diabetes and painful diabetic peripheral neuropathy, compared to placebo. Participants will either get an active medicine or a "dummy" medicine (placebo). Which treatment participants get is decided by chance. In this study the active, investigational medicine is called CagriSema. Doctors cannot yet prescribe CagriSema. For each participant, the study will last for about 10 months.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-27
• Study First Submitted QC: 2025-01-27
• Study Start: 2025-01-29
• Study First Posted: 2025-01-29
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-20
• Last Update Posted: 2025-04-22
• Primary Completion: 2026-08-21
• Study Completion: 2026-08-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

• Male or female.

• Age 18 years or above at the time of signing the informed consent.

• Body mass index (BMI) ≥25.0 kilogram per square meter (kg/m^2) at screening.

• Diagnosis of type 2 diabetes (T2D) ≥180 days before screening.

  • Stable daily and/or weekly dose(s) ≥90 days before screening of any of the following anti-diabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose, as judged by the investigator:
  • Treatment with 1-3 marketed oral anti-diabetic 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 insulin (including neutral protamine Hagedorn (NPH) insulin) according to local guidelines.

• HbA1c ≤10.5 % (91 millimole per mole [mmol/mol]) and ≥6.5 % (48 mmol/mol), as determined by central laboratory at screening.

• Diagnosis of painful diabetic peripheral neuropathy (pDPN) based on 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
  • Michigan Neuropathy Screening Instrument (MNSI) q≥4 or e≥2.5 at screening. AND
  • Douleur Neuropathique en 4 Questions (DN4) (Question 1 and 2) ≥4 at screening.

• The weekly average in Pain Intensity-Numerical Rating Scale (PI-NRS) score must meet the following criteria in both weeks during the screening period (day -15 to -8 and day -7 to -1):

  • Completion of daily PI-NRS reporting in the eDiary for a minimum of 4 out of 7 days each week. AND
  • The weekly average PI-NRS score must be ≥4.0. AND
  • The standard deviation (SD) of the weekly average PI-NRS score must be ≤2.0.

• 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).

Key

Exclusion Criteria

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
• Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), including medication with GLP-1 RA activity, or amylin analogue within 60 days before screening.
• Significant use of opioids, cannabinoids or benzodiazepines within 30 days before screening, in the opinion of the investigator.
• 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 corticosteroids).
• Planned initiation or change in anti-depressant, anti-psychotic or anti-epileptic medication. If participants are already taking such medication, they should have stable and optimised treatment for at least 8 weeks before screening.
• Presence or history of epilepsy and fibromyalgia.
• Presence of non-diabetic neuropathies, in the opinion of the investigator.
• 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.
• 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).
• History of suicidal attempt within 5 years before screening
• Suicidal behaviour within 1 month before screening.
• Renal impairment with estimated Glomerular Filtration Rate (eGFR) <30 ml/min/1.73 m2 as determined by central laboratory at screening.
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CagriSema	CagriSema (Cagrilintide B and Semaglutide I)	Participants will receive CagriSema (Cagrilintide B + Semaglutide I) subcutaneously once weekly in a dose escalation manner (dose increases every 4 weeks) for up to 16 weeks followed by CagriSema (Cagrilintide B + Semaglutide I) maintenance dose subcutaneously once weekly for 16 weeks.
Placebo	Placebo matched to CagriSema (Cagrilintide B and Semaglutide I)	Participants will receive placebo matched to CagriSema (Cagrilintide B + Semaglutide I) subcutaneously once weekly for 32 weeks.

Primary Outcome Measures

Name	Time	Method
Change in weekly average Pain Intensity-Numerical Rating Scale (PI-NRS)	From baseline (week 0) to end of treatment (week 32)	The PI-NRS measures the intensity of pain. It is a numerical scale ranging from 0 (indicating no pain) to 10 (representing the worst pain imaginable). Measured as score on a scale.

Secondary Outcome Measures

Name	Time	Method
Number of participants reaching ≥30 percentage (%) reduction in PI-NRS	From baseline (week 0) to end of treatment (week 32)	The PI-NRS measures the intensity of pain. It is a numerical scale ranging from 0 (indicating no pain) to 10 (representing the worst pain imaginable). Measured as count of participants.
Change in Chronic Pain Sleep Inventory 3-item (CPSI 3)	From baseline (week 0) to end of treatment (week 32)	The CPSI-3 measures the impact of chronic pain on sleep quality. It consists of 3 items and each item is rated on a scale where 0 represents 'never' and 100 represents 'always'. Higher scores indicate more frequent sleep disturbances and, consequently, a worse outcome in terms of sleep quality due to chronic pain. Measured as score on a scale.
Number of treatment-emergent adverse events (TEAEs)	From baseline (week 0) to end of study (week 38)	Measured as count of events.
Time to achieve ≥30% reduction in weekly average PI-NRS	From baseline (week 0) to end of treatment (week 32)	The PI-NRS measures the intensity of pain. It is a numerical scale ranging from 0 (indicating no pain) to 10 (representing the worst pain imaginable). Measured as days.
Time to achieve ≥50% reduction in weekly average PI-NRS	From baseline (week 0) to end of treatment (week 32)	The PI-NRS measures the intensity of pain. It is a numerical scale ranging from 0 (indicating no pain) to 10 (representing the worst pain imaginable). Measured as days.
Change in Brief Pain Inventory-Short Form (BPI-SF)	From baseline (week 0) to end of treatment (week 32)	The BPI-SF measures the severity of pain and the impact of pain on daily functions. It consists of two sections: Pain Severity and Pain Interference. Pain Severity is calculated as the average of four domains: Worst Pain, Least Pain, Average Pain, and Current Pain. Pain Interference is calculated as the average of seven domains: General Activity, Mood, Walking Ability, Normal Work, Relations with Other People, Sleep, and Enjoyment of Life. Each domain is measured on a scale from 0 to 10. Higher scores indicate more severe pain and greater interference with daily life. Measured as score on a scale.
Number of participants reaching ≥50 % reduction in PI-NRS	From baseline (week 0) to end of treatment (week 32)	The PI-NRS measures the intensity of pain. It is a numerical scale ranging from 0 (indicating no pain) to 10 (representing the worst pain imaginable). Measured as count of participants.
Change in Michigan Neuropathy Screening Instrument (MNSI)	From baseline (week 0) to end of treatment (week 32)	The MNSI is a specialised tool designed to screen for the presence of diabetic neuropathy. It consists of 2 parts: a 15-item questionnaire that assesses symptoms related to foot sensation, including pain, numbness, and temperature sensitivity. Each item can be answered 'yes' (1 point) or 'no (0 points). Higher scores indicate more neuropathic symptoms and patients with a total score \>4 points are considered to have neuropathy. a physical examination conducted by a health professional. Higher scores indicate more neuropathic symptoms and a physical assessment score ≥2.5 indicates a diagnosis of clinical neuropathy with a sensitivity and specificity of 61% and 95%, respectively. Measured as score on a scale.
Change in systolic blood pressure	From baseline (week 0) to end of treatment (week 32)	Measured as millimeters of mercury (mmHg).
Change in diastolic blood pressure	From baseline (week 0) to end of treatment (week 32)	Measured as mmHg.
Change in glycated haemoglobin (HbA1c)	From baseline (week 0) to end of treatment (week 32)	Measured as percentage of HbA1c.
Change in Fasting Plasma Glucose (FPG)	From baseline (week 0) to end of treatment (week 32)	Measured as millimole per liter (mmol/L).
Relative change in body weight	From baseline (week 0) to end of treatment (week 32)	Measured as percentage change.
Change in waist circumference	From baseline (week 0) to end of treatment (week 32)	Measured as centimeter (cm).
Ratio to Baseline in Lipids: Total Cholesterol	From baseline (week 0) to end of treatment (week 32)	Measured as ratio.
Ratio to Baseline in Lipids: High-density lipoprotein (HDL) cholesterol	From baseline (week 0) to end of treatment (week 32)	Measured as ratio.
Ratio to Baseline in Lipids: Low-density lipoprotein (LDL) cholesterol	From baseline (week 0) to end of treatment (week 32)	Measured as ratio.
Ratio to Baseline in Lipids: Very low-density lipoprotein (VLDL) cholesterol	From baseline (week 0) to end of treatment (week 32)	Measured as ratio.
Ratio to Baseline in Lipids: Triglycerides	From baseline (week 0) to end of treatment (week 32)	Measured as ratio.
Ratio to Baseline in Lipids: Free fatty acids	From baseline (week 0) to end of treatment (week 32)	Measured as ratio.
Ratio to Baseline in Lipids: Non-HDL cholesterol	From baseline (week 0) to end of treatment (week 32)	Measured as ratio.
Relative change in high sensitivity C-reactive protein (hsCRP)	From baseline (week 0) to end of treatment (week 32)	Measured as percentage change.
Number of treatment-emergent serious adverse events (TESAEs)	From baseline (week 0) to end of study (week 38)	Measured as count of events.
Number of severe hypoglycaemic episodes (level 3) (No specific glucose threshold)	From baseline (week 0) to end of study (week 38)	Severe hypoglycaemia is a severe event characterised by altered mental and/or physical status requiring assistance from another person to actively administer carbohydrates, glucagon, or take other corrective actions to treat hypoglycaemia. Measured as count of episodes.
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by blood glucose meter))	From baseline (week 0) to end of study (week 38)	Measured as count of episodes.

Trial Locations

Locations (47)

Steno Diabetes Center Odense; 🇩🇰 Odense C, Denmark

Kings College Hospital; 🇬🇧 London, United Kingdom

eStudySite; 🇺🇸 La Mesa, California, United States

Linda Vista Health Care Ctr; 🇺🇸 San Diego, California, United States

My Preferred Research; 🇺🇸 Miami, Florida, United States

New Horizon Research Center; 🇺🇸 Miami, Florida, United States

Renstar Medical Research; 🇺🇸 Ocala, Florida, United States

Foot & Ankle Center of Illinois; 🇺🇸 Springfield, Illinois, United States

Velocity Clinical Research Rockville; 🇺🇸 Rockville, Maryland, United States

Amicis Centers of Clinical Research; 🇺🇸 Saint Louis, Missouri, United States

Southgate Medical Group, LLP; 🇺🇸 West Seneca, New York, United States

Piedmont Healthcare/Research; 🇺🇸 Statesville, North Carolina, United States

Lillestol Research LLC; 🇺🇸 Fargo, North Dakota, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Clinical Res Collaborative; 🇺🇸 Cumberland, Rhode Island, United States

Radiance Clinical Research; 🇺🇸 Lampasas, Texas, United States

DM Clinical Research; 🇺🇸 San Antonio, Texas, United States

Velocity Clinical Research Portsmouth; 🇺🇸 Suffolk, Virginia, United States

G.A. Research Associates Ltd.; 🇨🇦 Moncton, New Brunswick, Canada

Premier Clinical Trial Research Network (PCTRN); 🇨🇦 Hamilton, Ontario, Canada

Diabetes Heart Research Centre; 🇨🇦 Toronto, Ontario, Canada

Ctr de Med Metab de Lanaudiere; 🇨🇦 Terrebonne, Quebec, Canada

Aarhus Universitetshospital, Steno Diabetes Center Aarhus; 🇩🇰 Aarhus N, Denmark

Steno Diabetes Center Nordjylland; 🇩🇰 Gistrup, Denmark

Steno Diabetes Center Cph_Steno Diabetes Center Cph; 🇩🇰 Herlev, Denmark

Kolding Sygehus Karkirurgi; 🇩🇰 Kolding, Denmark

Les Hopitaux de Chartres-Hopital Louis Pasteur; 🇫🇷 Le Coudray, France

Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-1; 🇫🇷 Le Creusot, France

Aphp-Hopital La Pitie Salpetriere-1; 🇫🇷 Paris, France

Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-1; 🇫🇷 Pessac, France

Centre de Recherche Clinique Portes Du Sud; 🇫🇷 Venissieux, France

Haukeland Universitetssykehus; 🇳🇴 Bergen, Norway

Sykehuset Innlandet HF Hamar; 🇳🇴 Hamar, Norway

Oslo universitetssykehus, Ullevål; 🇳🇴 Oslo, Norway

Stavanger Universitetssykehus, Helse Stavanger HF; 🇳🇴 Stavanger, Norway

Hospital Nisa Sevilla Aljarafe; 🇪🇸 Castilleja De La Cuesta. Sevilla, Andalucia, Spain

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Complejo Hospitalario Universitario A Coruña; 🇪🇸 La Coruña, Spain

Hospital Universitario de la Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain

Hospital Infanta Luisa; 🇪🇸 Sevilla, Spain

Tameside General Hospital; 🇬🇧 Ashton-Under-Lyne, Greater Manchester, United Kingdom

Ipswich Hospital_ESNEFT; 🇬🇧 Ipswich, United Kingdom

University Hospital Aintree; 🇬🇧 Liverpool, United Kingdom

Manchester Royal Infirmary; 🇬🇧 Manchester, United Kingdom

Royal Hallamshire Hospital; 🇬🇧 Sheffield, United Kingdom