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NCT02466516

Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination With Simtuzumab (SIM) in Adults With Nonalcoholic Steatohepatitis (NASH) and Fibrosis Stages F2-F3

Completed Phase 2 Results posted Last updated 26 June 2019
What this trial tests

Phase 2 trial testing SEL in Non-Alcoholic Steatohepatitis (NASH) in 72 participants. Completed in 11 October 2016.

Timeline
8 June 2015
Primary endpoint
11 October 2016
11 October 2016

Quick facts

Lead sponsorGilead Sciences
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment72
Start date8 June 2015
Primary completion11 October 2016
Estimated completion11 October 2016
Sites28 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

Adults 18 to 70, any sex, with Non-Alcoholic Steatohepatitis (NASH). 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.

Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality Primary · Baseline up to last dose plus 30 days (up to Week 28)

Treatment-emergent events began on or after the first dosing date up to 30 days after the last dosing date or led to premature discontinuation of study drug. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.

TEAEs
GroupValue95% CI
SEL 6 mg17
SEL 18 mg15
SEL 6 mg+SIM 125 mg9
SEL 18 mg+SIM 125 mg9
SIM 125 mg7
SAEs
GroupValue95% CI
SEL 6 mg2
SEL 18 mg2
SEL 6 mg+SIM 125 mg0
SEL 18 mg+SIM 125 mg1
SIM 125 mg0
Any Grade ≥ 1 Laboratory Abnormality
GroupValue95% CI
SEL 6 mg17
SEL 18 mg21
SEL 6 mg+SIM 125 mg9
SEL 18 mg+SIM 125 mg10
SIM 125 mg8
Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events Primary · Baseline up to follow up visit (Week 28)
Discontinued Study Drug
GroupValue95% CI
SEL 6 mg1
SEL 18 mg2
SEL 6 mg+SIM 125 mg0
SEL 18 mg+SIM 125 mg0
SIM 125 mg0
Discontinued Study
GroupValue95% CI
SEL 6 mg1
SEL 18 mg1
SEL 6 mg+SIM 125 mg0
SEL 18 mg+SIM 125 mg0
SIM 125 mg0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to last dose plus 30 days (up to Week 28). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

SEL 6 mg
Serious: 2/20 (10%)
Deaths: 0/20
SEL 18 mg
Serious: 2/22 (9%)
Deaths: 0/22
SEL 6 mg+SIM 125 mg
Serious: 0/10 (0%)
Deaths: 0/10
SEL 18 mg+SIM 125 mg
Serious: 1/10 (10%)
Deaths: 0/10
SIM 125 mg
Serious: 0/10 (0%)
Deaths: 0/10

Serious adverse events (11 terms)

ReactionSystemSEL 6 mgSEL 18 mgSEL 6 mg+SIM 125 mgSEL 18 mg+SIM 125 mgSIM 125 mg
Cardiac failure congestiveCardiac disorders
Abdominal painGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
BronchitisInfections and infestations
InfluenzaInfections and infestations
PneumoniaInfections and infestations
SepsisInfections and infestations
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
HypoaesthesiaNervous system disorders
Transient ischaemic attackNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Other adverse events (99 terms — click to expand)

ReactionSystemSEL 6 mgSEL 18 mgSEL 6 mg+SIM 125 mgSEL 18 mg+SIM 125 mgSIM 125 mg
HeadacheNervous system disorders
Abdominal pain upperGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
NasopharyngitisInfections and infestations
SinusitisInfections and infestations
Urinary tract infectionInfections and infestations
Musculoskeletal painMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FlatulenceGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
InfluenzaInfections and infestations
Procedural painInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Abnormal dreamsPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
AlopeciaSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
FlushingVascular disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal tendernessGastrointestinal disorders
Aphthous ulcerGastrointestinal disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
Infrequent bowel movementsGastrointestinal disorders
Oral painGastrointestinal disorders
Palatal swellingGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
Chest discomfortGeneral disorders
Chest painGeneral disorders
ChillsGeneral disorders
Hernia painGeneral disorders
Injection site bruisingGeneral disorders
Injection site erythemaGeneral disorders

Most-reported serious reactions: Cardiac failure congestive, Abdominal pain, Rectal haemorrhage, Bronchitis, Influenza, Pneumonia, Sepsis, Musculoskeletal chest pain.

Data from ClinicalTrials.gov NCT02466516 adverse events section.

Sponsor's own description

The primary objective of this study is to evaluate the safety and tolerability of GS-4997 (selonsertib \[SEL\]) alone or in combination with simtuzumab (SIM) in adults with nonalcoholic steatohepatitis (NASH) and fibrosis stages F2-F3. Participants will be randomized in a 2:2:1:1:1 ratio to 1 of 5 study treatment arms.

Publications & conference data

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

  1. Hepatic stellate cells as key target in liver fibrosis.
    Higashi T, Friedman SL, Hoshida Y. · · 2017 · cited 1148× · PMID 28506744 · DOI 10.1016/j.addr.2017.05.007
  2. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine.
    Fujiwara N, Friedman SL, Goossens N, Hoshida Y. · · 2018 · cited 519× · PMID 28989095 · DOI 10.1016/j.jhep.2017.09.016
  3. Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).
    Xu X, Poulsen KL, Wu L, Liu S, et al · · 2022 · cited 235× · PMID 35963848 · DOI 10.1038/s41392-022-01119-3
  4. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review.
    Singh S, Osna NA, Kharbanda KK. · · 2017 · cited 169× · PMID 29085205 · DOI 10.3748/wjg.v23.i36.6549
  5. The JNK Signaling Pathway in Renal Fibrosis.
    Grynberg K, Ma FY, Nikolic-Paterson DJ. · · 2017 · cited 166× · PMID 29114233 · DOI 10.3389/fphys.2017.00829
  6. 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
  7. ASK1 contributes to fibrosis and dysfunction in models of kidney disease.
    Liles JT, Corkey BK, Notte GT, Budas GR, et al · · 2018 · cited 121× · PMID 30024858 · DOI 10.1172/jci99768
  8. Pathophysiology and Treatment Options for Hepatic Fibrosis: Can It Be Completely Cured?
    Khanam A, Saleeb PG, Kottilil S. · · 2021 · cited 86× · PMID 34064375 · DOI 10.3390/cells10051097

Verify or expand the search:

Other trials of SEL

Trials testing the same drug.

Other recruiting trials for Non-Alcoholic Steatohepatitis (NASH)

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/NCT02466516.

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