Last reviewed · How we verify

NCT03987074

Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)

Completed Phase 2 Results posted Last updated 15 July 2021
What this trial tests

Phase 2 trial testing Semaglutide in Nonalcoholic Steatohepatitis in 109 participants. Completed in 13 July 2020.

Timeline
29 July 2019
Primary endpoint
13 July 2020
13 July 2020

Quick facts

Lead sponsorGilead Sciences
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment109
Start date29 July 2019
Primary completion13 July 2020
Estimated completion13 July 2020
Sites18 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

Adults 18 to 75, any sex, with Nonalcoholic Steatohepatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Primary · First dose date up to Week 24 plus 30 days

Treatment-emergent adverse events (TEAEs) were defined as, any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. Participants were assessed for AEs according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

GroupValue95% CI
Semaglutide81.0
Semaglutide + Firsocostat 20 mg86.4
Semaglutide + Cilofexor 30 mg81.8
Semaglutide + Cilofexor 100 mg72.7
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg90.5
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Primary · First dose date up to 24 weeks plus 30 days

Treatment-emergent laboratory abnormalities, defined as values that increase at least one toxicity grade from baseline at any time post-baseline up to and including the date of last dose of study drug plus 30 days, were summarized by treatment group. Graded laboratory abnormalities were defined using the grading scheme in the CTCAE 5.0.

Grade 1
GroupValue95% CI
Semaglutide61.9
Semaglutide + Firsocostat 20 mg63.6
Semaglutide + Cilofexor 30 mg36.4
Semaglutide + Cilofexor 100 mg50.0
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg66.7
Grade 2
GroupValue95% CI
Semaglutide23.8
Semaglutide + Firsocostat 20 mg22.7
Semaglutide + Cilofexor 30 mg31.8
Semaglutide + Cilofexor 100 mg18.2
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg9.5
Grade 3
GroupValue95% CI
Semaglutide0.0
Semaglutide + Firsocostat 20 mg4.5
Semaglutide + Cilofexor 30 mg0.0
Semaglutide + Cilofexor 100 mg0.0
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg0.0
Grade 4
GroupValue95% CI
Semaglutide0.0
Semaglutide + Firsocostat 20 mg0.0
Semaglutide + Cilofexor 30 mg0.0
Semaglutide + Cilofexor 100 mg9.1
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg0.0

Adverse events — posted to ClinicalTrials.gov

Time frame: First dose date up to 24 weeks plus 30 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Semaglutide
Serious: 1/21 (5%)
Deaths: 0/21
Semaglutide + Firsocostat 20 mg
Serious: 0/22 (0%)
Deaths: 0/22
Semaglutide + Cilofexor 30 mg
Serious: 0/22 (0%)
Deaths: 0/22
Semaglutide + Cilofexor 100 mg
Serious: 1/22 (5%)
Deaths: 0/22
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg
Serious: 0/21 (0%)
Deaths: 0/21

Serious adverse events (3 terms)

ReactionSystemSemaglutideSemaglutide + Firsocostat …Semaglutide + Cilofexor 30…Semaglutide + Cilofexor 10…Semaglutide + Firsocostat …
DiarrhoeaGastrointestinal disorders
PancreatitisGastrointestinal disorders
VomitingGastrointestinal disorders
Other adverse events (29 terms — click to expand)

ReactionSystemSemaglutideSemaglutide + Firsocostat …Semaglutide + Cilofexor 30…Semaglutide + Cilofexor 10…Semaglutide + Firsocostat …
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
HypoglycaemiaMetabolism and nutrition disorders
Abdominal distensionGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Early satietyGeneral disorders
FatigueGeneral disorders
GastroenteritisInfections and infestations
DizzinessNervous system disorders
HeadacheNervous system disorders
Vision blurredEye disorders
Visual impairmentEye disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
EructationGastrointestinal disorders
PyrexiaGeneral disorders
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Blood creatine phosphokinase increasedInvestigations
Weight decreasedInvestigations
DysuriaRenal and urinary disorders
Rhinitis allergicRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Diarrhoea, Pancreatitis, Vomiting.

Data from ClinicalTrials.gov NCT03987074 adverse events section.

Sponsor's own description

The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in participants with nonalcoholic steatohepatitis (NASH).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus.
    Ferguson D, Finck BN. · · 2021 · cited 370× · PMID 34131333 · DOI 10.1038/s41574-021-00507-z
  2. Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics.
    Jin HR, Wang J, Wang ZJ, Xi MJ, et al · · 2023 · cited 284× · PMID 37700339 · DOI 10.1186/s13045-023-01498-2
  3. Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial.
    Alkhouri N, Herring R, Kabler H, Kayali Z, et al · · 2022 · cited 165× · PMID 35439567 · DOI 10.1016/j.jhep.2022.04.003
  4. Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.
    Wu X, Xu M, Geng M, Chen S, et al · · 2023 · cited 161× · PMID 37244925 · DOI 10.1038/s41392-023-01439-y
  5. Treatments for NAFLD: State of Art.
    Mantovani A, Dalbeni A. · · 2021 · cited 147× · PMID 33652942 · DOI 10.3390/ijms22052350
  6. Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges.
    Dufour JF, Caussy C, Loomba R. · · 2020 · cited 145× · PMID 32381514 · DOI 10.1136/gutjnl-2019-319104
  7. Evolving Role for Pharmacotherapy in NAFLD/NASH.
    Attia SL, Softic S, Mouzaki M. · · 2021 · cited 100× · PMID 32583961 · DOI 10.1111/cts.12839
  8. Nonalcoholic Fatty Liver Disease (NAFLD). Mitochondria as Players and Targets of Therapies?
    Di Ciaula A, Passarella S, Shanmugam H, Noviello M, et al · · 2021 · cited 93× · PMID 34065331 · DOI 10.3390/ijms22105375

Verify or expand the search:

Other trials of Semaglutide

Trials testing the same drug.

Other recruiting trials for Nonalcoholic Steatohepatitis

Currently open trials in the same condition.

Other Gilead Sciences trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03987074.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing