Skip to main content
. 2021 Sep 23;54(10):1243–1262. doi: 10.1111/apt.16602

TABLE 1.

Recent and ongoing clinical trials (phase 2 or higher) with steroidal and non‐steroidal FXR agonists

Substance Trial phase Study population Endpoints Results Status* Reference
Cilofexor (GS9674) II PSC (< F4) Primary: safety at W12 (randomised; vs placebo)

  • No safety concerns

  • Cilofexor reduced ALP, GGT, ALT, AST

  • Cilofexor reduced C4 and BA levels

  • Pruritus: 14%–20% in cilofexor vs 40% in placebo group

 Completed NCT02943460 153
Cilofexor (GS9674) III PSC (< F4)

Primary: fibrosis progression at W96 (randomised; vs placebo)

Secondary: ALP, GGT, ALT, AST, BA, hepatic collagen, histological changes, fibrosis biomarkers

  • No results published

 Recruiting PRIMIS NCT03890120
Cilofexor (GS9674) II NASH (< F4) Primary: safety at W24 (randomised; vs placebo)

  • No safety concerns

  • Hepatic fat fraction −22.7% in cilofexor vs +1.9% in placebo group

  • Cilofexor reduced GGT, C4, BA levels

 Completed NCT02854605 155
Cilofexor (GS9674) II NASH (< F4) Primary: safety at W24 (randomised; Semaglutide, Firsocostat, Cilofexor in different combinations; no placebo)

  • No results published

 Completed NCT03987074
Cilofexor (GS9674) II NASH (No dACLD) Primary: safety at W12 (different combinations of selonsertib, firsocostat, cilofexor, fenofibrate, icosapent ethyl; no placebo)

  • No results published

 Completed NCT02781584
Cilofexor (GS9674) II NASH (F3/F4) (No dACLD) Primary: safety, ≥1 stage fibrosis improvement without NASH worsening at W48 (randomised; Selonsertib, Firsocostat, Cilofexor vs placebo)

  • No effect on primary endpoint across all treatment regimens

  • No effect by cilofexor on hepatic collagen proportion on liver biopsy

  • Cilofexor/firsocostat improved histological NASH activity

  • Cilofexor/firsocostat reduced ALT/AST, ELF score, liver stiffness

 Completed ATLAS NCT03449446 156
OCA II PBC (No dACLD)

Primary: ALP change at W12 (randomised; combination with UDCA; vs placebo)

Secondary: GGT, ALT, PK

  • OCA reduced ALP, GGT and ALT

  • Pruritus: 50% in placebo group; similar in 10mg (47%) OCA group, higher in 25mg (87%) and 50mg (80%) groups

 Completed NCT00550862 184
OCA II PBC (No dACLD)

Primary: ALP change at W12 (randomised; vs placebo)

Secondary: GGT, AST, ALT, bilirubin

  • OCA reduced ALP

  • Pruritus: 35% in placebo group, higher in in 10mg OCA (70%) and in 50mg OCA (94%) groups

 Completed NCT00570765 185
OCA II PBC (No dACLD)

Primary: ALP change at W12 (randomised; in different combinations with bezafibrate)

Secondary: AST, ALT, GGT, bilirubin, life quality, BA, C4

  • No results published

 Recruiting NCT04594694
OCA III PBC (No dACLD)

Primary: ALP <1.67 ULN and −15%, normal bilirubin at 12 months (UDCA non‐responders; randomised; vs placebo)

Secondary: ALP, bilirubin, AST, ALT, GGT

  • Composite endpoint met by 10% in placebo group, 46% in 5‐10mg OCA, 47% in 10mg OCA groups

  • Pruritus: 38% in placebo group, 56% in 5‐10mg OCA, 68% in 10mg OCA groups

  • More SAEs in OCA groups

 Completed POISE NCT01473524 147 , 148
OCA IV PBC (No dACLD)

Primary: composite endpoint of hepatic decompensation, MELD ≥15, LT, death (randomised; vs placebo)

Secondary: decompensation, death, HCC, fibrosis markers, FGF19, liver dysfunction

  • No results published

 Recruiting COBALT NCT02308111
OCA II PSC (No dACLD)

Primary: ALP change at W24 (randomised; vs placebo)

Secondary: AST, ALT, bilirubin, GGT, FGF19, C4

  • OCA reduced ALP, but not bilirubin levels

  • Pruritus: 46% in placebo group, 60%–67% in OCA group

 Completed AESOP NCT02177136 152
OCA II NASH (No dACLD) Primary: LDL concentration and particle size at W16 (randomised; combination with statins; vs placebo)

  • OCA increased LDL concentration and LDL particle size

  • Atorvastatin normalised LDL levels

 Completed CONTROL NCT02633956 186
OCA II NASH (< F4)

Primary: histological NAS score at W72 (randomised; vs placebo)

Secondary: NASH resolution, fibrosis improvement, histological NAS components, serum markers of glucose tolerance, systemic haemodynamics, BMI, life quality

  • OCA improved liver histology in 45%; vs 21% in placebo group (RR 1.9, 1.3‐2.8)

  • OCA increased VLDL and LDL

  • Pruritus: 6% in placebo group, 23% in OCA group

 Completed FLINT NCT01265498 187 , 188
OCA III NASH (< F4)

Primary: fibrosis improvement without NASH worsening, or NASH resolution without fibrosis worsening; decompensation and mortality at 18 months (randomised, vs placebo)

Secondary: histological dynamics, liver biochemistry

  • Interim analysis: significant improvement of fibrosis, but no higher rate of NASH resolution

  • Pruritus: 19% in placebo group, 28% in 10mg OCA, 51% in 25mg OCA groups

 Active, not recruiting REGENERATE NCT02548351 154
OCA II DM type 2

Primary: insulin resistance at W6 (randomised; vs placebo)

Secondary: liver dysfunction markers

  • OCA increased insulin sensitivity (24.5% in combined OCA group vs 5.5% in placebo group)

  • OCA reduced GGT and ALT

  • OCA increased FGF19 and decreased BA levels

 Completed NCT00501592 189
OCA II Obese and gallstone patients

Primary: insulin resistance, triglycerides, expression of transport proteins and ER stress markers (randomised; vs placebo)

Secondary: serum lipid levels

  • OCA increased FGF19 levels

  • OCA decreased C4 and BA levels

  • OCA decreased BA concentration and increased hydrophobicity index in the gallbladder

  • OCA induced FGF19 expression in gallbladder epithelium

 Completed OCABSGS NCT01625026 190
OCA II BA diarrhea Primary: FGF19 changes (non‐randomised, open label)

  • OCA increased FGF19 levels

  • OCA decreased C4 and BA levels

  • OCA improved stool frequency, stool form, and diarrhea index

 Completed OBADIAH1 NCT01585025 145
OCA II Familial Partial Lipodystrophy Primary: change liver triglycerides at W8 (randomised; vs placebo)

  • No results published

 Recruiting NCT02430077
OCA II ALD (Acute AH)

Primary: MELD score, safety (randomised; vs placebo)

Secondary: bacterial translocation, intestinal inflammation, cytokines

  • Terminated due to hepatotoxicity concerns

 Terminated TREAT NCT02039219
PX104 II NAFLD (No dACLD)

Primary: Safety at W4; (non‐randomised)

Secondary: hepatic fat (%), oGTT, FGF19, plasma BA, PK

  • Early termination due to 2 cases of cardiac arrhythmia

  • PX104 decreased ALP and GGT

  • PX104 improved insulin sensitivity

 Terminated NCT01999101 191
Tropifexor (LJN452) II PBC (No dACLD)

Primary: GGT, RR, HR, Temperature, ECG, Hb at W4/W12 (randomised; vs placebo)

Secondary: PK, PBC‐40 score, pruritus

  • Interim analysis: Tropifexor induced dose‐dependent decline of GGT and ALT

  • Final results pending

 Completed NCT02516605 192
Tropifexor (LJN452) II NASH (< F4)

Primary: Safety, TA levels, hepatic fat (%) at W12 (randomised; vs placebo)

Secondary: GGT, FGF19, fibrosis biomarkers, lipid profile, pruritus, BMI, serum C4

  • Interim analysis: Tropifexor reduced hepatic fat fraction, ALT, and body weight

  • Final results pending

 Completed FLIGHT‐FXR NCT02855164 157
Tropifexor (LJN452) II NASH (F2/F3)

Primary: Safety at W48 (randomised; monotherapy vs combination with cenicriviroc)

Secondary: fibrosis improvement (>1 point), NASH resolution

  • No results published

 Completed TANDEM NCT03517540
Tropifexor (LJN452) II NASH (F2/F3)

Primary: fibrosis improvement without NASH worsening, NASH resolution without fibrosis worsening at W48 (randomised; monotherapy vs placebo vs combination with licogliflozin)

Secondary: NASH resolution, fibrosis improvement, body weight, hepatic fat (%), AST, ALT, GGT, safety

  • No results published

 Recruiting ELIVATE NCT04065841

Abbreviations: AH, alcoholic hepatitis; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BA, bile acids; BMI, body‐mass index; c/dACLD, compensated/decompensated advanced chronic liver disease; C4, serum 7‐alpha‐hydroxy‐4‐cholesten‐3‐one; DM, diabetes mellitus; ECG, electrocardiography; FGF19, fibroblast growth factor 19; GGT, gamma‐glutamyl transferase; Hb, haemoglobin; HCC, hepatocellular carcinoma; HDL, high density lipoprotein; HR, heart rate; LT, liver transplantation; MELD, Model of End Stage Liver Disease score; NAS, NAFLD activity score; NASH, non‐alcoholic steatohepatitis; OCA, obeticholic acid; oGTT, oral glucose tolerance test; PBC, primary biliary cholangitis; PK, pharmacokinetics; PSC, primary sclerosing cholangitis; RR, blood pressure; SAE, serious adverse event; UDCA, ursodeoxycholic acid; ULN, upper limit of normal; V/LDL, (very) low density lipoprotein.

*

Trial status was obtained from “ClinicalTrials.gov”.