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NNC0194-0499

Phase 2

Non-alcoholic Steatohepatitis | Small molecule | Infectious Disease |Novo Nordisk A/S|Last Updated: Nov 19, 2025

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials3
Total Enrollment793
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT05016882Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)PHASE2 COMPLETED 698Aug 31, 2021Mar 14, 2025Nov 19, 2025255 United States, Australia +22
NCT05766709A Research Study Comparing Blood Levels of Medicines NNC0194-0499 and Semaglutide Administered as a Combination Formulation Versus Two Separate FormulationsPHASE1 COMPLETED 53Mar 2, 2023Feb 9, 2024Feb 29, 20241 Canada
NCT04722653A Research Study Looking at How the Medicine NNC0194-0499 Behaves in Japanese and Non-Asian MenPHASE1 COMPLETED 42Feb 2, 2021Apr 27, 2021Apr 5, 20221 Japan
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Study Endpoints
Primary Endpoints
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

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

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

Secondary Endpoints
Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No)
From baseline (week 0) to week 52
Improvement in steatohepatitis with at least a 2-point reduction in NAS and no worsening of fibrosis (Yes/No)
From baseline (week 0) to week 52
Change in histology-assessed liver collagen proportionate area
From baseline (week 0) to week 52
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
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.
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.
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.
Interventions
NameTypeDescription
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
NNC0194-0499DRUGNNC0194-0499 will be administered subcutaneously once weekly.
SemaglutideDRUGSemaglutide will be administered subcutaneously once weekly.
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.
Placebo (NNC0194-0499 )DRUG1 single dose administered subcutaneously (s.c. - under the skin).
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Eligibility Criteria
Age Range18 Years — 55 Years
SexALL
Healthy VolunteersNo
Study Sites255

Inclusion Criteria: * Aged greater than or equal to 18 years at the time of signing informed consent. In Republic of Korea, subjects must be aged greater than or equal to 19 years. In Japan, subjects must be aged greater than or equal to 20 years. In Singapore, subjects must be aged greater than or...

Countries:United StatesAustraliaBelgiumBulgariaCanadaCzechiaDenmarkFranceGermanyGreeceIndiaItalyJapanMalaysiaPolandPortugalPuerto RicoRussiaSingaporeSouth KoreaSpainTaiwanTurkey (Türkiye)United Kingdom
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