A research study to investigate the effects of CagriSema compared to placebo in people with type 2 diabetes and painful diabetic peripheral neuropathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

22 Jan 2025 → ongoing

Decision date (initial)

2024-12-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-509662-38-00

WHO UTN

U1111-1306-9422

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate the superiority of Semaglutide + Cagrilintide s.c. 0.0 mg/0.0 mg once weekly versus placebo with respect to reduction of neuropathic pain in participants with type 2 diabetes (T2D) and painful diabetic peripheral neuropathy (pDPN)

Secondary objectives 4

1. To compare the effect of Semaglutide + Cagrilintide s.c. 0.0 mg/0.0 mg once weekly versus placebo on neuropathic pain in participants with T2D and pDPN
2. To compare the effect of Semaglutide + Cagrilintide s.c. 0.0 mg/0.0 mg once weekly versus placebo on clinical outcomes assessments (COAs) in participants with T2D and Pdpn
3. To compare the effect of Semaglutide + Cagrilintide s.c. 0.0 mg/0.0 mg once weekly versus placebo in participants with T2D and pDPN with respect to: Blood pressure, Parameters of glycaemic control, Body weight, Waist circumference, Lipids, Inflammation
4. To compare the safety and tolerability of Semaglutide + Cagrilintide s.c. 0.0 mg/0.0 mg once weekly versus placebo in participants with T2D and pDPN

Conditions and MedDRA coding

Type 2 diabetes and painful diabetic peripheral neuropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male or female.
2. Age 18 years or above at the time of signing the informed consent.
3. Body mass index (BMI) ≥25.0 kg/m2 at screening.
4. 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.
5. HbA1c ≤10.5 % (91 mmol/mol) and ≥6.0 % (42 mmol/mol), as determined by central laboratory at screening.
6. 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.
7. 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.
8. 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 14

1. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
2. 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.
3. 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.
4. 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).
5. 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.
6. Presence or history of epilepsy.
7. Presence or history of fibromyalgia.
8. Presence of non-diabetic neuropathies, in the opinion of the investigator.
9. 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.
10. 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).
11. History of suicidal attempt within 5 years before screening.
12. Suicidal behaviour within 1 month before screening.
13. Renal impairment with estimated Glomerular Filtration Rate (eGFR) <30 ml/min/1.73 m2 as determined by central laboratory at screening.
14. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in weekly average Pain Intensity-Numerical Rating Scale (PI-NRS)

Secondary endpoints 19

1. Participants reaching ≥30 % reduction in PI-NRS Pain (yes/no)
2. Time to achieve ≥30% reduction in weekly average PI-NRS Pain
3. Participants reaching ≥50 % reduction in PI-NRS Pain (yes/no)
4. Time to achieve ≥50% reduction in weekly average PI-NRS Pain
5. Change in Brief Pain Inventory-Short Form (BPI-SF)
6. Change in Chronic Pain Sleep Inventory 3-item (CPSI 3)
7. Change in Michigan Neuropathy Screening Instrument (MNSI)
8. Change in systolic blood pressure
9. Change in diastolic blood pressure
10. Change in glycated haemoglobin (HbA1c)
11. Change in Fasting Plasma Glucose (FPG)
12. Relative change in body weight
13. Change in waist circumference
14. 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
15. Relative change in high-sensitivity C-reactive protein (hsCRP)
16. Number of treatment-emergent adverse events (TEAEs)
17. Number of treatment-emergent serious adverse events (TESAEs)
18. Number of severe hypoglycaemic episodes (level 3)
19. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter))

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 9

Locations

4 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications