A Research Study Comparing Blood Levels of Medicines NNC0194-0499 and Semaglutide Administered as a Combination Formulation Versus Two Separate Formulations

Investigation of Pharmacokinetics Following Administration of NNC0194-0499 and Semaglutide as Co-formulation Versus Separate Injections in Healthy Participants

Novo Nordisk is developing a combination of 2 medicines (NNC0194-0499 and semaglutide) for the treatment of nonalcoholic steatohepatitis (NASH). NASH is a serious disease where fat, inflammation and scar tissue builds up in the liver. NNC0194-0499 is a new medicine which works in the liver. Semaglutide is a well-known medicine, which is already used to treat type 2 diabetes and obesity. The study is being done to see how 2 medicines (NNC0194-0499 and semaglutide) are absorbed, transported, and eliminated from the body in a combination formulation. Participants will either get NNC0194-0499 and semaglutide in a combination formulation or the separate formulations. Which treatment participants get is decided by chance. The study will last for either 13 or 33 weeks. The duration is decided by chance.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: Semaglutide; Drug: NNC0194-0499; Drug: NNC0194-0499/Semaglutide A (40/3.20 mg/mL); Drug: NNC0194-0499/Semaglutide A (40/0.33mg/mL)

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3P 3P1
      • Altasciences Company Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female
• Aged 18-55 years (both inclusive) at the time of signing informed consent
• Body mass index (BMI) between greater than or equal to 25 and less than or equal to 35 kilogram per meter square (kg/m^2) (both inclusive)
• 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:

• Known or suspected hypersensitivity to study intervention(s) or related products
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive method
• Participation (that is, signed informed consent) in any other interventional clinical study within 90 days before first trial product administration (Visit 2, Day 1)
• Use of prescription medicinal products or non-prescription drugs, except routine vitamins, topical medication, highly effective contraceptives and occasional use of paracetamol, acetylsalicylic acid within 14 days before first trial product administration (Visit 2, Day 1)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Participants will receive separate injections of NNC0194-0499 B and Semaglutide B for 24 weeks. Dose escalation manner every 4 weeks for 20 weeks (30 mg NNC0194-0499 B and 0.24 mg Semaglutide B for Weeks 1-4, 30 mg NNC0194-0499 B and 0.5 mg Semaglutide B for Weeks 5-8, 30 mg NNC0194-0499 B and 1.0 mg Semaglutide B for Weeks 9-12, 30 mg NNC0194-0499 B and 1.7 mg Semaglutide B for Weeks 13-16 and 30 mg NNC0194-0499 B and 2.4 mg Semaglutide B for Weeks 17-20). Participants will receive NNC0194-0499/Semaglutide A 40/3.20 mg/mL co-formulation at the target dose of 30/2.4 mg during the weeks 21-24 (maintenance dosing period).	Drug: Semaglutide; Semaglutide will be administered subcutaneously once weekly.; Drug: NNC0194-0499; NNC0194-0499 will be administered subcutaneously once weekly.; Drug: NNC0194-0499/Semaglutide A (40/3.20 mg/mL); NNC0194-0499/Semaglutide A (40/3.20 mg/mL) co-formulation product will be administered subcutaneously once weekly.
Experimental: Group 2; Participants will receive NNC0194-0499/Semaglutide A 40/3.20 mg/mL co-formulation for 24 weeks. Dose escalation manner every 4 weeks for 20 weeks (3.1mg/0.25mg for Weeks 1-4, 6.3mg/0.5mg for Weeks 5-8, 12.5mg/1.0mg for Weeks 9-12, 21.3mg/1.7mg for Weeks 13-16 and 30mg/2.4mg for weeks 17-20). Participants will receive NNC0194-0499/Semaglutide 40/3.20 mg/mL co-formulation at the target dose of 30mg/2.4mg during the weeks 21-24 (maintenance dosing period).	Drug: NNC0194-0499/Semaglutide A (40/3.20 mg/mL); NNC0194-0499/Semaglutide A (40/3.20 mg/mL) co-formulation product will be administered subcutaneously once weekly.
Experimental: Group 3; Participants will receive 4 weekly injections of NNC0194-0499/Semaglutide A 40/0.33 mg/mL co-formulation at the dose level of 30mg/0.25 mg.	Drug: NNC0194-0499/Semaglutide A (40/0.33mg/mL); NNC0194-0499/Semaglutide A (40/0.33mg/mL) will be administered subcutaneously once weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC 0-168 hour (h), 0499, steady state (SS): Area under the NNC0194-0499 concentration time curve during a dosing interval (0-168 hours) at steady state after dosing of NNC0194-0499 in combination with semaglutide	Measured as nanomoles*hours per liter (nmol*h/L)	Day 134 (pre-dose) to Day 141 (168 hours post-dose)
AUC 0-168h,sema,SS: Area under the semaglutide concentration time curve during a dosing interval (0-168 hours) at steady state after dosing of NNC0194-0499 in combination with semaglutide	Measured as nmol*h/L	Day 134 (pre-dose) to Day 141 (168 hours post-dose)
Cmax, 0499, SS: Maximum concentration of NNC0194-0499 at steady state after dosing of NNC0194-0499 in combination with semaglutide	Measured as nanomoles per liter (nmol/L)	Day 134 (pre-dose) to Day 141 (168 hours post-dose)
Cmax,sema, SS: Maximum concentration of semaglutide at steady state after dosing of NNC0194-0499 in combination with semaglutide	Measured as nmol/L	Day 134 (pre-dose) to Day 141 (168 hours post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC 0-168h, 0499, SS: Area under the NNC0194-0499 concentration-time curve during a dosing interval (0-168 hours) at steady state after dosing of NNC0194-0499 in combination with semaglutide	Measured as nmol*h/L	Day 22 (pre-dose) to Day 29 (168 hours post-dose)
AUC 0-168h, sema , SS: Area under the semaglutide concentration-time curve during a dosing interval (0-168 hours) at steady state after dosing of semaglutide in combination with NNC0194-0499	Measured as nmol*h/L	Day 22 (pre-dose) to Day 29 (168 hours post-dose)
Cmax, 0499, SS: Maximum concentration of NNC0194-0499 at steady state after dosing of NNC0194-0499 in combination with semaglutide	Measured as nmol/L	Day 22 (pre-dose) to Day 29 (168 hours post-dose)
Cmax, sema , SS: Maximum concentration of semaglutide at steady state after dosing of semaglutide in combination with NNC0194-0499	Measured as nmol/L	Day 22 (pre-dose) to Day 29 (168 hours post-dose)
Number of treatment emergent adverse events	Measured as count of events	Day 1 (post-dose) to Day 197 (Groups 1 and 2) and Day 1 (post-dose) to Day 57 (Group 3)

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): March 2, 2023
• Primary Completion (Actual): January 5, 2024
• Study Completion (Actual): February 9, 2024

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: March 9, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NN9500-4932; U1111-1285-5065 (Other Identifier: World Health Organization (WHO))

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