Clinical trial NCT06797869: A Research Study to Investigate the Effects of CagriSema Compared to Placebo in People With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy
Official title: Efficacy and Safety of co Administered Cagrilintide and Semaglutide (CagriSema) Once Weekly Versus Placebo in Participants With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Diabetic Peripheral Neuropathy
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2025-01-29
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

  -- For participants on anti-diabetic drugs: 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 or basal-bolus insulin (including premixed insulin formulations) according to local guidelines.
* HbA1c ≤10.5 % (91 millimole per mole \[mmol/mol\]) and ≥6.0 % (42 mmol/mol), as determined by central laboratory at screening.
* Diagnosis of painful diabetic peripheral neuropathy (pDPN) at screening as well as at the following criteria:

  -- Participant with self-reported pain consistent with pDPN for a minimum of 3 months before screening, as judged by the investigator.
* 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, (DPP-4), 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. Significant use is defined as use that renders it unlikely that the participant is able to comply with protocol requirements for discouraged medications.
* 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.

Primary outcomes:
measure: Change in weekly average Pain Intensity-Numerical Rating Scale (PI-NRS)
timeFrame: From baseline (week 0) to end of treatment (week 32)
Secondary outcomes:
measure: Number of participants reaching ≥30 percentage (%) reduction in PI-NRS
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Time to achieve ≥30% reduction in weekly average PI-NRS
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Number of participants reaching ≥50 % reduction in PI-NRS
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Time to achieve ≥50% reduction in weekly average PI-NRS
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Change in Brief Pain Inventory-Short Form (BPI-SF)
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Change in Chronic Pain Sleep Inventory 3-item (CPSI 3)
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Change in Michigan Neuropathy Screening Instrument (MNSI)
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Change in systolic blood pressure
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Change in diastolic blood pressure
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Change in glycated haemoglobin (HbA1c)
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Relative change in body weight
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Change in waist circumference
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Ratio to Baseline in Lipids: Total Cholesterol
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Ratio to Baseline in Lipids: High-density lipoprotein (HDL) cholesterol
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Ratio to Baseline in Lipids: Low-density lipoprotein (LDL) cholesterol
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Ratio to Baseline in Lipids: Very low-density lipoprotein (VLDL) cholesterol
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Ratio to Baseline in Lipids: Triglycerides
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Ratio to Baseline in Lipids: Free fatty acids
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Ratio to Baseline in Lipids: Non-HDL cholesterol
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Relative change in high sensitivity C-reactive protein (hsCRP)
timeFrame: From baseline (week 0) to end of treatment (week 32)
measure: Number of treatment-emergent adverse events (TEAEs)
timeFrame: From baseline (week 0) to end of study (week 38)
measure: Number of treatment-emergent serious adverse events (TESAEs)
timeFrame: From baseline (week 0) to end of study (week 38)
measure: Number of severe hypoglycaemic episodes (level 3) (No specific glucose threshold)
timeFrame: From baseline (week 0) to end of study (week 38)
measure: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by blood glucose meter))
timeFrame: From baseline (week 0) to end of study (week 38)
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: eStudySite
state: California
city: San Diego
country: United States
facility: Linda Vista Health Care Ctr
state: California
city: Miami
country: United States
facility: My Preferred Research
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Springfield
country: United States
facility: Foot & Ankle Center of Illinois
state: Illinois
city: Rockville
country: United States
facility: Velocity Clinical Research Rockville
state: Maryland
city: Saint Louis
country: United States
facility: Amicis Centers of Clinical Research
state: Missouri
city: West Seneca
country: United States
facility: Southgate Medical Group, LLP
state: New York
city: Statesville
country: United States
facility: Piedmont Healthcare/Research
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Cumberland
country: United States
facility: Clinical Res Collaborative
state: Rhode Island
city: Lampasas
country: United States
facility: Radiance Clinical Research
state: Texas
city: San Antonio
country: United States
facility: DM Clinical Research
state: Texas
city: Suffolk
country: United States
facility: Velocity Clinical Research Portsmouth
state: Virginia
city: Moncton
country: Canada
facility: G.A. Research Associates Ltd.
state: New Brunswick
city: Hamilton
country: Canada
facility: Premier Clinical Trial Research Network (PCTRN)
state: Ontario
city: Toronto
country: Canada
facility: Diabetes Heart Research Centre
state: Ontario
city: Terrebonne
country: Canada
facility: Ctr de Med Metab de Lanaudiere
state: Quebec
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Steno Diabetes Center Aarhus
city: Gistrup
country: Denmark
facility: Steno Diabetes Center Nordjylland
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Kolding
country: Denmark
facility: Kolding Sygehus Karkirurgi
city: Odense C
country: Denmark
facility: Steno Diabetes Center Odense
city: Le Coudray
country: France
facility: Les Hopitaux de Chartres-Hopital Louis Pasteur
city: Le Creusot
country: France
facility: Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-1
city: Paris
country: France
facility: Aphp-Hopital La Pitie Salpetriere-1
city: Pessac
country: France
facility: Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-1
city: Venissieux
country: France
facility: Centre de Recherche Clinique Portes Du Sud
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Hamar
country: Norway
facility: Sykehuset Innlandet HF Hamar
city: Oslo
country: Norway
facility: Oslo universitetssykehus, Ullevål
city: Stavanger
country: Norway
facility: Stavanger Universitetssykehus, Helse Stavanger HF
city: Castilleja De La Cuesta. Sevilla
country: Spain
facility: Hospital Nisa Sevilla Aljarafe
state: Andalucia
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa
city: Ashton-Under-Lyne
country: United Kingdom
facility: Tameside General Hospital
state: Greater Manchester
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital_ESNEFT
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
city: London
country: United Kingdom
facility: St Pancras Clinical Research
city: London
country: United Kingdom
facility: Kings College Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: