A Research Study Investigating the Effect of NNC0497-0040 in Healthy Participants, Participants With Overweight or Obesity, and Participants With Type 1 Diabetes With Overweight or Obesity

Investigation of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous Weekly Doses of NNC0497-0040 in Healthy Participants, Participants With Overweight or Obesity, and in Participants With Type 1 Diabetes With Overweight or Obesity

The purpose of this clinical study is to find out if NNC0497-0040 is safe, tolerable and effective for healthy people living with normal weight or overweight, people living with overweight or obesity and people who have type 1 diabetes and are living with overweight or obesity. There are 2 study treatments in this study, where participants will get either NNC0497-0040, the new treatment being tested or placebo, a treatment that has no active medicine in it. Participants will be in this clinical study for up to 29 weeks.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Overweight; Healthy Volunteers; Type 1 Diabetes (T1D)
• Intervention / Treatment: Drug: Placebo; Drug: NNC0497-0040

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Recruiting
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

For SAD cohorts

Inclusion Criteria:

• Female of non-childbearing potential or male aged 18-55 years (both inclusive) at screening.
• Body mass index between 18.5 kilogram per m^2 and 29.9 kilogram per m^2 (both inclusive) at screening.
• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Exclusion Criteria:

• Any disorder, unwillingness or inability which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.
• Glycated haemoglobin (HbA1c) above or equal to 6.5 percentage (48 millimoles per mole) at screening.
• Unwilling or unable to refrain from use of prescription medicinal products or non-prescription drugs, including use of herbal products and non-routine vitamins, within 14 days prior to the first day of dosing. Occasional use of paracetamol and ibuprofen to treat acute pain is permitted until 24 hours prior to dosing.

For MAD1-3 cohorts

Inclusion Criteria:

• Female of non-childbearing potential or male aged 18-55 years (both inclusive) at screening.
• Body mass index between 27.0 kilogram per m^2 and 39.9 kilogram per m^2 (both inclusive) at screening. Overweight should be due to excess adipose tissue, as judged by the investigator.
• Considered eligible based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Exclusion Criteria:

• Any disorder, unwillingness or inability which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.
• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions.
• HbA1c above or equal to 6.5 percentage (48 millimoles per mole) at screening.
• Unwilling or unable to refrain from use of prescription medicinal products or non-prescription drugs, including use of herbal products and non-routine vitamins, within 14 days prior to the first day of dosing. Occasional use of paracetamol and ibuprofen to treat acute pain is permitted until 24 hours prior to dosing.

For MAD4 cohorts

Inclusion Criteria:

• Male aged 18-55 years (both inclusive) at screening.
• Body mass index between 27.0 kilogram per m^2 and 34.9 kilogram per m^2 (both inclusive) at screening. Overweight should be due to excess adipose tissue, as judged by the investigator.
• Diagnosed with type 1 diabetes mellitus above or equal to 1 year before screening.
• Treated with multiple daily insulin injections (daily basal insulin analogue and bolus insulin analogue regimen) more than 90 days prior to the day of screening.
• Use of continuous glucose monitoring (CGM) device more than 90 consecutive days prior to the day of screening.
• HbA1c in the range of 7.2percentage - 9.5percentage (both inclusive).

Exclusion Criteria:

• Any disorder, unwillingness or inability, except for mild conditions under stable treatment associated with type 1 diabetes (T1D), which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.
• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological conditions (except conditions associated with diabetes mellitus and obesity).
• Use of any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening or in the period between screening and randomisation.
• Current treatment with systemically effective corticosteroids, monoamine oxidase (MAO) inhibitors, systemic non-selective beta-blockers or growth hormone.
• Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g., treatment with orlistat, thyroid hormones, or corticosteroids).
• Unwilling or unable to refrain from use of prescription medicinal products or non-prescription drugs, including use of herbal products and non-routine vitamins, within 14 days prior to the first day of dosing. Occasional use of paracetamol and ibuprofen to treat acute pain is permitted until 24 hours prior to dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAD; Participants will receive NNC0497-0040 or placebo matched to NNC0497-0040 subcutaneously.	Drug: Placebo; Placebo will be administered subcutaneously.; Drug: NNC0497-0040; NNC0497-0040 will be administered subcutaneously.
Experimental: MAD1; Participants will receive NNC0497-0040 or placebo matched to NNC0497-0040 subcutaneously.	Drug: Placebo; Placebo will be administered subcutaneously.; Drug: NNC0497-0040; NNC0497-0040 will be administered subcutaneously.
Experimental: MAD2; Participants will receive NNC0497-0040 or placebo matched to NNC0497-0040 subcutaneously.	Drug: Placebo; Placebo will be administered subcutaneously.; Drug: NNC0497-0040; NNC0497-0040 will be administered subcutaneously.
Experimental: MAD3; Participants will receive NNC0497-0040 or placebo matched to NNC0497-0040 subcutaneously.	Drug: Placebo; Placebo will be administered subcutaneously.; Drug: NNC0497-0040; NNC0497-0040 will be administered subcutaneously.
Experimental: MAD4; Participants will receive NNC0497-0040 or placebo matched to NNC0497-0040 subcutaneously.	Drug: Placebo; Placebo will be administered subcutaneously.; Drug: NNC0497-0040; NNC0497-0040 will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	Measured in events	Day 1 up to Week 6
Number of adverse events	Measured in events	MAD1-2: Day 1 up to Week 17; MAD3: Day 1 up to Week 25
Number of adverse events	Measured in events	Day 1 up to Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum NNC0497-0040 concentration time curve	Measured in hours * nanomoles per litre (h*nmol/L)	Day 1
Cmax: Maximum observed serum NNC0497-0040 concentration	Measured in nanomoles per litre (nmol/L)	Day 1
Area under the serum NNC0497-0040 concentration time curve at steady state	Measured in hours * nanomoles per litre (h*nmol/L)	MAD1-2: Week 12; MAD3: Week 20
Cmax: Maximum observed serum NNC0497-0040 concentration at steady state	Measured in nanomoles per litre (nmol/L)	MAD1-2: Week 12; MAD3: Week 20
Number of severe hypoglycaemic episodes	Measured in events	Day 1 up to Week 25
AUC: Area under the serum NNC0497-0040 concentration time curve during at steady state	Measured in hours * nanomoles per litre (h*nmol/L)	MAD4: Week 20
Cmax: Maximum observed serum NNC0497-0040 concentration at steady state	Measured in nanomoles per litre (nmol/L)	MAD4: Week 20

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency dept. 2834, Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2026
• Primary Completion (Estimated): February 18, 2028
• Study Completion (Estimated): February 18, 2028

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 1
• Other Study ID Numbers: NN6497-8309; U1111-1325-4319 (Other Identifier: World Health Organization (WHO)); 2025-523978-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes