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NCT03486912: FALCON 2

A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Liver Cirrhosis

Completed Phase 2 Results posted Last updated 13 October 2022
What this trial tests

Phase 2 trial testing BMS-986036 in Hepatic Cirrhosis in 155 participants. Completed in 14 September 2021.

Timeline
12 June 2018
Primary endpoint
8 October 2020
14 September 2021

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment155
Start date12 June 2018
Primary completion8 October 2020
Estimated completion14 September 2021
Sites91 locations across Japan, United States

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

Adults 18 to 75, any sex, with Hepatic Cirrhosis or Liver Fibrosis. 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.

The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 48 Primary · From first dose to 48 weeks after first dose

An improvement in fibrosis is defined as a decrease of fibrosis by ≥1-stage in the NASH Clinical Research Network (CRN) Fibrosis Score at week 48 in liver biopsy. Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease activity score (NAS) by ≥ 1-stage. Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) by ≥1 point. Worsening of fibrosis is defined as an increase of fibrosis by ≥1 point as determined by the NASH CRN Fibrosis Score.

GroupValue95% CI
BMS-986036 10 mg28.2
BMS-986036 20 mg24.3
BMS-986036 40 mg28.2
Placebo30.8
The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Ishak Fibrosis Score at Week 48 Secondary · From first dose to 48 weeks after first dose

An improvement in Ishak fibrosis is defined as a decrease of fibrosis by ≥ 1-stage in the Ishak fibrosis score at week 48 in liver biopsy. ISHAKs uses a 0-6 scale: 1: centrilobular pericellular fibrosis, 2: centrilobular and periportal fibrosis, 3: bridging fibrosis (few bridges), 4: bridging fibrosis (many bridges), 5: early or incomplete cirrhosis, 6: established or advanced cirrhosis.

GroupValue95% CI
BMS-986036 10 mg38.5
BMS-986036 20 mg32.4
BMS-986036 40 mg33.3
Placebo35.9
The Percentage of Participants With Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) or NASH Improvement at Week 48 Secondary · From first dose to 48 weeks after first dose

The percentage of participants who achieved a ≥1-stage improvement in fibrosis without worsening of NASH or NASH improvement with no worsening of fibrosis at week 48 in liver biopsy. Improvement in fibrosis is defined by the NASH Clinical Research Network (CRN) Fibrosis Score. Improvement in NASH is defined by a ≥2-stage decrease in the nonalcoholic fatty liver disease activity score (NAS). NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).

GroupValue95% CI
BMS-986036 10 mg33.3
BMS-986036 20 mg40.5
BMS-986036 40 mg35.9
Placebo30.8
The Percentage of Participants Who Achieved >=1 Point Improvement in Fibrosis at Week 48 Secondary · From first dose to 48 weeks after first dose

An improvement in fibrosis is defined as a decrease of ≥ 1-stage in the non-alcoholic steatohepatitis clinical research network (NASH CRN) Fibrosis Score at week 48 in liver biopsy. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).

GroupValue95% CI
BMS-986036 10 mg35.9
BMS-986036 20 mg29.7
BMS-986036 40 mg28.2
Placebo33.3
The Percentage of Participants With Any Improvement in Collagen Proportionate Area (CPA) at Week 48 Secondary · From first dose to 48 weeks after first dose

An improvement in CPA is defined as any decrease in CPA at week 48 in liver biopsy.

GroupValue95% CI
BMS-986036 10 mg61.8
BMS-986036 20 mg54.2
BMS-986036 40 mg41.9
Placebo53.1
The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution at Week 48 Secondary · From first dose to 48 weeks after first dose

NASH resolution defined by the nonalcoholic fatty liver disease activity score (NAS) component of ballooning = 0 and inflammation = 0-1 at week 48 in liver biopsy. Ballooning = 0 (none) inflammation = 0 (none) - 1 (Grade \<2).

GroupValue95% CI
BMS-986036 10 mg2.6
BMS-986036 20 mg5.4
BMS-986036 40 mg2.6
Placebo0.0
The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement at Week 48 Secondary · From first dose to 48 weeks after first dose

The percentage of participants with NASH improvement at week 48 in liver biopsy. NASH improvement is defined as a reduction of nonalcoholic fatty liver disease activity score (NAS) by ≥ 2 points with contribution from \> 1 NAS component. The NASH CRN system assesses liver biopsies for degree of steatosis (0-3), lobular inflammation (0-3), hepatocellular ballooning (0-2), and fibrosis (0-4). The 3 categories are added together in an unweighted fashion to determine the NAS, which ranges from 0 to 8.

GroupValue95% CI
BMS-986036 10 mg15.4
BMS-986036 20 mg24.3
BMS-986036 40 mg12.8
Placebo2.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Participants were assessed for All-Cause Mortality from their randomization until the study was completed (up to approximately 39 months). SAEs and Other AEs were assessed from first dose to 30 days following last dose (up to approximately 52 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BMS-986036 10 mg
Serious: 7/39 (18%)
Deaths: 1/39
BMS-986036 20 mg
Serious: 7/37 (19%)
Deaths: 0/38
BMS-986036 40 mg
Serious: 8/39 (21%)
Deaths: 0/39
Placebo
Serious: 3/39 (8%)
Deaths: 1/39

Serious adverse events (30 terms)

ReactionSystemBMS-986036 10 mgBMS-986036 20 mgBMS-986036 40 mgPlacebo
Clostridium difficile infectionInfections and infestations
AnaemiaBlood and lymphatic system disorders
Acute coronary syndromeCardiac disorders
Coronary artery diseaseCardiac disorders
Supraventricular tachycardiaCardiac disorders
AscitesGastrointestinal disorders
PancreatitisGastrointestinal disorders
Cholecystitis acuteHepatobiliary disorders
CholelithiasisHepatobiliary disorders
AppendicitisInfections and infestations
COVID-19Infections and infestations
COVID-19 pneumoniaInfections and infestations
DiverticulitisInfections and infestations
Norovirus infectionInfections and infestations
Comminuted fractureInjury, poisoning and procedural complications
Meniscus injuryInjury, poisoning and procedural complications
Tibia fractureInjury, poisoning and procedural complications
DehydrationMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
ArthritisMusculoskeletal and connective tissue disorders
Cerebral haemorrhageNervous system disorders
Spondylitic myelopathyNervous system disorders
SyncopeNervous system disorders
Acute kidney injuryRenal and urinary disorders
Glomerulonephritis membranoproliferativeRenal and urinary disorders
Other adverse events (68 terms — click to expand)

ReactionSystemBMS-986036 10 mgBMS-986036 20 mgBMS-986036 40 mgPlacebo
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Injection site bruisingGeneral disorders
Abdominal painGastrointestinal disorders
Frequent bowel movementsGastrointestinal disorders
FatigueGeneral disorders
Increased appetiteMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Injection site erythemaGeneral disorders
NasopharyngitisInfections and infestations
SinusitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
HeadacheNervous system disorders
Abdominal distensionGastrointestinal disorders
ConstipationGastrointestinal disorders
BronchitisInfections and infestations
HypoglycaemiaMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
Skin lesionSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Varices oesophagealGastrointestinal disorders
Injection site painGeneral disorders
Ear infectionInfections and infestations
ContusionInjury, poisoning and procedural complications
Procedural painInjury, poisoning and procedural complications
White blood cells urine positiveInvestigations
Type 2 diabetes mellitusMetabolism and nutrition disorders
Vitamin D deficiencyMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
RashSkin and subcutaneous tissue disorders
PalpitationsCardiac disorders
Abdominal tendernessGastrointestinal disorders
FlatulenceGastrointestinal disorders
VomitingGastrointestinal disorders
Injection site reactionGeneral disorders
Injection site swellingGeneral disorders

Most-reported serious reactions: Clostridium difficile infection, Anaemia, Acute coronary syndrome, Coronary artery disease, Supraventricular tachycardia, Ascites, Pancreatitis, Cholecystitis acute.

Data from ClinicalTrials.gov NCT03486912 adverse events section.

Sponsor's own description

This is a study of experimental medication BMS-986036 given to adults with Nonalcoholic Steatohepatitis (NASH; the buildup of fat and inflammation in the liver that is not caused by alcohol) and liver cirrhosis (liver damage characterized by normal liver tissue being replaced by scar tissue).

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. NAFLD: Mechanisms, Treatments, and Biomarkers.
    Nassir F. · · 2022 · cited 245× · PMID 35740949 · DOI 10.3390/biom12060824
  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. 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
  5. New targets for NAFLD.
    Parlati L, Régnier M, Guillou H, Postic C. · · 2021 · cited 128× · PMID 34667947 · DOI 10.1016/j.jhepr.2021.100346
  6. 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
  7. 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
  8. Nuclear Receptors Linking Metabolism, Inflammation, and Fibrosis in Nonalcoholic Fatty Liver Disease.
    Puengel T, Liu H, Guillot A, Heymann F, et al · · 2022 · cited 75× · PMID 35269812 · DOI 10.3390/ijms23052668

Verify or expand the search:

Other trials of BMS-986036

Trials testing the same drug.

Other recruiting trials for Hepatic Cirrhosis

Currently open trials in the same condition.

Other Bristol-Myers Squibb trials

Trials by the same sponsor.

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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/NCT03486912.

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