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NNC0194-0499

Phase 2

Alcohol-related Liver Disease | Small molecule | Gastrointestinal |Novo Nordisk A/S|Last Updated: Aug 13, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment270

FDA Designations

No designations recorded

Clinical trial landscape

NNC0194-0499 · 11 trials · 10 indications

Phase 2 2Phase 1 9
NCT06409130Effects of NNC0194-0499, Cagrilintide, and Semaglutide Alone or in Combinations on Liver Damage and Alcohol Use in People With Alcohol-related Liver DiseaseAlcohol-related Liver Disease
COMPLETED270 Analytics
NCT05016882Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)Non-alcoholic Steatohepatitis
COMPLETED698 Analytics
PHASE2COMPLETED
Effects of NNC0194-0499, Cagrilintide, and Semaglutide Alone or in Combinations on Liver Damage and Alcohol Use in People With Alcohol-related Liver Disease
Alcohol-related Liver DiseaseUnlock trial analytics
PHASE2COMPLETED
Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)
Non-alcoholic SteatohepatitisUnlock trial analytics

Study Endpoints

Primary Endpoints

Change in Enhanced Liver Fibrosis (ELF)
From week 0 to week 28

Measured as logarithm score

Improvement in liver fibrosis and no worsening of NASH (Yes/No)
From baseline (week 0) to week 52

Count of subjects Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale

Part A: Change in time in range (TIR) 3.9-10.0 mmol/L (70-80 mg/dL)
From baseline (day -14 - -1) to day 36-49 / day 106-119

Percentage point (%-points).

Part B: Change in time in range (TIR) 3.9-10.0 mmol/L (70-80 mg/dL)
From baseline (day -14 - -1) to day 92-105 / day 162-175

%-points.

(AUC0-24h,EE,SS), area under the ethinylestradiol plasma concentration-time curve during a dosing interval at steady state
Day 8 (pre-dose to 24 hours post-dose) and Day 38 (pre-dose to 24 hours post-dose)

h-pg/mL

(AUC0-24h,LN,SS), area under the levonorgestrel plasma concentration-time curve during a dosing interval at steady state
Day 8 (pre-dose to 24 hours post-dose) and Day 38 (pre-dose to 24 hours post-dose)

h-pg/mL

AUC0-∞, Single Dose, NNC0194-0499: the area under the NNC0194-0499 serum concentration-time curve from time 0 to infinity after a single dose
From 0 hours (Day 1) until end of study visit (Day 36)

Measured in nanomoles hour per liter (nmol h/L).

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
Day 134 (pre-dose) to Day 141 (168 hours post-dose)

Measured as nanomoles\*hours per liter (nmol\*h/L)

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
Day 134 (pre-dose) to Day 141 (168 hours post-dose)

Measured as nmol\*h/L

Cmax, 0499, SS: Maximum concentration of NNC0194-0499 at steady state after dosing of NNC0194-0499 in combination with semaglutide
Day 134 (pre-dose) to Day 141 (168 hours post-dose)

Measured as nanomoles per liter (nmol/L)

Cmax,sema, SS: Maximum concentration of semaglutide at steady state after dosing of NNC0194-0499 in combination with semaglutide
Day 134 (pre-dose) to Day 141 (168 hours post-dose)

Measured as nmol/L

AUC0-∞, NNC0194-0499: The area under the NNC0194-0499 serum concentration-time curve from time 0 to infinity after a single dose
From Day 1 (pre-dose) until completion of the post-treatment follow-up visit (Day 36)

Measured in nanomoles\*hours per liter (nmol h/L).

AUC0499,0-∞,SD: Area under the NNC0194-0499 serum concentration-time curve after a single dose
From baseline (Visit 2, Day 1, pre-dose) until completion of the end of study visit (Visit 9, Day 36)

Measured as hours\*nanomoles per litre (h\*nmol/L)

Number of treatment emergent adverse events (TEAEs)
From Day 1 (pre-dose) until completion of the post-treatment period at follow-up (Day 36)

Count of events

Number of treatment-emergent adverse events (TEAEs)
From time of administration of NNC0194-0499 (day 1) to completion of the post-treatment period at follow-up (day 36)

Secondary Endpoints

Change in Pro-peptide of Collagen 3 (Pro-C3)
From week 0 to week 28
Change in liver stiffness assessed by Vibration Controlled Transient Elastography (VCTE)
From week 0 to week 28
Change in liver steatosis assessed by Controlled Attenuated Parameter (CAP)
From week 0 to week 28
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
NNC0194-0499 + semaglutideEXPERIMENTALGroup A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide.
NNC0194-0499 + semaglutide placeboEXPERIMENTALGroup A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide placebo.
NNC0194-0499 placebo + semaglutideEXPERIMENTALGroup A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide.
NNC0194-0499 placebo + semaglutide placeboPLACEBO_COMPARATORGroup A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide placebo.
CagriSemaEXPERIMENTALGroup B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide.
Cagrilintide + semaglutide placeboEXPERIMENTALGroup B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide placebo.
Cagrilintide placebo + semaglutide placeboPLACEBO_COMPARATORGroup B: Participants will receive subcutaneous (s.c.) injection of cagrilintide placebo in combination with semaglutide placebo.
NNC0194-0499 7.5 mg + semaglutide 2.4 mgEXPERIMENTALEach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo (NNC0194-0499) 7.5 mg + semaglutide placebo 2.4 mgPLACEBO_COMPARATOREach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
NNC0194-0499 15 mg + semaglutide 2.4 mgEXPERIMENTALEach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo (NNC0194-0499) 15 mg + semaglutide placebo 2.4 mgPLACEBO_COMPARATOREach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
NNC0194-0499 30 mg + semaglutide 2.4 mgEXPERIMENTALEach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
NNC0194-0499 30 mg + semaglutide placebo 2.4 mgEXPERIMENTALEach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo (NNC0194-0499) 30 mg + semaglutide 2.4 mgACTIVE_COMPARATOREach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo (NNC0194-0499) 30 mg + semaglutide placebo 2.4 mgPLACEBO_COMPARATOREach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
NNC0174-0833 2.4 mg + semaglutide 2.4 mgEXPERIMENTALEach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo (NNC0174-0833) 2.4 mg + semaglutide placebo 2.4 mgPLACEBO_COMPARATOREach subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Part A: NNC0194-0499/PlaceboEXPERIMENTALAfter a 2-week run-in period; participants will be randomised 1:1 to a treatment sequence with two 7-week treatment periods of once weekly subcutaneous NNC0194-0499 or placebo. Between the two treatment periods; there is a wash-out period. After the wash-out period, there will be a cross over, ensuring that all the participants receive both NNC0194-0499 and placebo.
Part B: NNC0194-0499/Placebo + SemaglutideEXPERIMENTALAfter the 2-week run-in phase followed by the 8-week of dose escalation period (every 4 weeks) of once weekly subcutaneous semaglutide; participants will be randomised 1:1 to a treatment sequence with two 7-week treatment periods of once weekly subcutaneous NNC0194-0499 or placebo and continued semaglutide. Between the two treatment periods; there is a wash-out period where the participant continues to receive once weekly subcutaneous semaglutide. After the wash-out period, there will be a cross over, ensuring that all the participants receive both NNC0194-0499 and placebo together with semaglutide.
Sequence 1EXPERIMENTALAll participants will be exposed to both interventions in a defined sequence. OC 8 days, NNC0194-0499 4 weeks, OC/NNC0194-0499 combined 1 week.
Participants With Normal Hepatic FunctionEXPERIMENTALParticipants with normal hepatic function will receive a single subcutaneous dose of 30 milligram (mg) of NNC0194-0499 on Day 1.
Participants With Mild Hepatic ImpairmentEXPERIMENTALParticipants with mild hepatic impairment (Child Pugh Grade A) will receive a single subcutaneous dose of 30 mg of NNC0194-0499 on Day 1.
Participants With Moderate Hepatic ImpairmentEXPERIMENTALParticipants with moderate hepatic impairment (Child-Pugh Grade B) will receive a single subcutaneous dose of 30 mg of NNC0194-0499 on Day 1.
Participants With Severe Hepatic ImpairmentEXPERIMENTALParticipants with severe hepatic impairment (Child-Pugh Grade C) will receive a single subcutaneous dose of 30 mg of NNC0194-0499 on Day 1.
Group 1EXPERIMENTALParticipants 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).
Group 2EXPERIMENTALParticipants 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).
Group 3EXPERIMENTALParticipants 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.
NNC0194-0499 12 mgEXPERIMENTALParticipants will receive a single subcutaneous (s.c.) dose of 12 milligrams (mg) NNC0194-0499 on Day 1.
NNC0194-0499 30 mgEXPERIMENTALParticipants will receive a single s.c. dose of 30 mg NNC0194-0499 on Day 1.
NNC0194-0499 96 mgEXPERIMENTALParticipants will receive a single s.c. dose of 96 mg NNC0194-0499 on Day 1.
Participants with normal renal functionACTIVE_COMPARATORParticipants will receive a single subcutaneous injection of 30 mg NNC0194-0499.
Participants with impaired renal functionEXPERIMENTALParticipants will receive a single subcutaneous injection of 30 mg NNC0194-0499.
NN0194-0499EXPERIMENTALJapanese participants will be randomised 3:1 to receive either a single dose of NNC0194-0499 or placebo, Asian participants will only receive NNC0194-0499. There will be 3 cohorts with escalating dose levels. There should be at least 4 days between dose administration of the last participant in a dose level cohort and dose administration of the first participant in the following dose level cohort.
PlaceboPLACEBO_COMPARATORJapanese participants will be randomised 3:1 to receive either a single dose of NNC0194-0499 or placebo.
NNC0194-0499EXPERIMENTALParticipants will receive increasing doses of NNC0194-0499. The treatment period from first treatment (Day 1) to end of the treatment (Day 85) will be 12 weeks.

Interventions

NameTypeDescription
NNC0194-0499DRUGAdministered subcutaneously.
SemaglutideDRUGAdministered subcutaneously.
NNC0194-0499 placeboDRUGAdministered subcutaneously.
Semaglutide placebo (Group A)DRUGAdministered subcutaneously.
Cagrilintide + semaglutideDRUGAdministered subcutaneously.
CagrilintideDRUGAdministered subcutaneously.
Cagrilintide placeboDRUGAdministered subcutaneously.
Semaglutide placebo (Group B)DRUGAdministered subcutaneously.
NNC0194 0499 50 mg/mLDRUGPatients will receive subcutaneous (s.c., under the skin) injections of NNC0194-0499 once weekly The study will last for about 19 months
Placebo (NNC0194-0499)DRUGPatients will receive subcutaneous (s.c., under the skin) injections of placebo once weekly The study will last for about 19 months
Semaglutide 3 mg/mLDRUGPatients will receive subcutaneous (s.c., under the skin) injections of semaglutide once weekly The study will last for about 19 months
Semaglutide placeboDRUGPatients will receive subcutaneous (s.c., under the skin) injections of semaglutide placebo once weekly The study will last for about 19 months
NNC0174 0833 10 mg/mLDRUGPatients will receive subcutaneous (s.c., under the skin) injections of NNC0174-0833 once weekly The study will last for about 19 months
NNC0174 0833 placeboDRUGPatients will receive subcutaneous (s.c., under the skin) injections of NNC0174-0833 placebo once weekly The study will last for about 19 months
PlaceboDRUGParticipants will receive placebo matched to NNC0194-0499 subcutaneously.
ethinylestradiol/levonorgestrelDRUGOral contraceptive is taken as tablet daily composed of 30 μg ethinylestradiol and 150 μg levonorgestrel.
NNC0194-0499/Semaglutide A (40/3.20 mg/mL)DRUGNNC0194-0499/Semaglutide A (40/3.20 mg/mL) co-formulation product will be administered subcutaneously once weekly.
NNC0194-0499/Semaglutide A (40/0.33mg/mL)DRUGNNC0194-0499/Semaglutide A (40/0.33mg/mL) will be administered subcutaneously once weekly.
NC0194-0499DRUGParticipants will receive a single s.c. dose of 96 mg NNC0194-0499 on Day 1.
Placebo (NNC0194-0499 )DRUG1 single dose administered subcutaneously (s.c. - under the skin).
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites102

Inclusion Criteria: * Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study. * Age 18 years or above, and at the legal drinking age according t...

Countries:United StatesAustraliaBulgariaCanadaCzechiaDenmarkFranceGermanyGreeceItalyJapanNetherlandsPolandSpainBelgiumIndiaMalaysiaPortugalPuerto RicoRussiaSingaporeSouth KoreaTaiwanTurkey (Türkiye)United KingdomAustriaSlovakiaChina
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Recent Changes (Last 90 Days)

LOWAug 14, 2026NCT07087795lastUpdatePostDate: changed
LOWAug 14, 2026NCT07087795lastUpdatePostDate: changed
LOWAug 14, 2026NCT07087795lastUpdatePostDate: changed

Frequently asked questions about NNC0194-0499

What is NNC0194-0499 used for?

NNC0194-0499 is an investigational small molecule being developed by Novo Nordisk for several conditions, including hepatic impairment, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease, and type 1 diabetes. It is currently in Phase 2 clinical development and is not yet approved by regulatory authorities.

Who makes NNC0194-0499?

NNC0194-0499 is being developed by Novo Nordisk A/S, a pharmaceutical company listed on the stock exchange under the ticker NVO. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various liver and metabolic conditions.

What phase is NNC0194-0499 in?

NNC0194-0499 is currently in Phase 2 clinical development. The drug is investigational and has not been approved by the FDA or any other regulatory agency. It has completed several Phase 1 trials and is being studied for conditions such as NASH and type 1 diabetes.

What clinical trials is NNC0194-0499 in?

NNC0194-0499 has been studied in several clinical trials, including NCT05727644, which examined blood and urine levels in participants with reduced kidney function, and NCT05742919, which looked at how a single dose behaves in Chinese men. NCT06188026 studied its interaction with birth control pills, and NCT07087795 is an active trial evaluating it alone or with semaglutide for type 1 diabetes.

Is NNC0194-0499 being studied for type 1 diabetes?

Yes, NNC0194-0499 is being studied for type 1 diabetes. An active clinical trial, NCT07087795, is evaluating the effect of NNC0194-0499 alone or in combination with semaglutide on blood sugar control in people living with type 1 diabetes. This trial is currently in Phase 1 and is not yet recruiting participants.