ELATIVE

15 evidence topics · 3 sources

Objective

Biochemical-response objective

“biochemical response at Week 52” (opens the source at this quote in a new tab)

Location and study date

No evidence found.

Study design

Randomized multicenter design

“multi-center, randomized, double-blind, placebo-controlled study” (opens the source at this quote in a new tab)

Eligibility criteria

Biochemical eligibility

Criterion	Quoted threshold
ALP: at least this multiple of ULN	“1.67”
Total bilirubin: at most this multiple of ULN	“2”

Treatment

Daily treatment allocation

Treatment	Dose
Elafibranor	“80 mg”
Comparator	“placebo”

Study outcomes

Rationale for using ALP and bilirubin biochemical response as the primary endpoint

ALP and bilirubin as prognostic markers

“Combining levels of alkaline phosphatase and bilirubin increased the ability to predict patient survival times.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Randomized population

Treatment	Participants
Elafibranor	“108”
Placebo	“53”

Description of analysis sets

Early treatment cessation or rescue treatment before week 52

“non-responders” (opens the source at this quote in a new tab)

Primary response analysis

“exact Cochran–Mantel–Haenszel (CMH) test” (opens the source at this quote in a new tab)

Results

Participant disposition

No evidence found.

Baseline characteristics

Baseline population

Characteristic	Reported value
Mean age, years	“57”
Female participants	“96%”
Mean ALP, U/L	“321.9”

Efficacy results

Week 52 biochemical results

Outcome	Elafibranor	Placebo
Biochemical response, n (%)	“55 (51)”	“2 (4)”
ALP normalization, n (%)	“16 (15)”	“0 (0)”

Week 52 biochemical response and alkaline phosphatase normalization: between-group differences

“A biochemical response (the primary end point) was observed in 51% of the patients (55 of 108) who received elafibranor and in 4% (2 of 53) who received placebo, for a difference of 47 percentage points (95% confidence interval [CI], 32 to 57; P<0.001).” (opens the source at this quote in a new tab)
“The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group at week 52 (difference, 15 percentage points; 95% CI, 6 to 23; P=0.002).” (opens the source at this quote in a new tab)
“Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

Week 52 pruritus: moderate-to-severe pruritus subgroup

“Among patients who had moderate-to-severe pruritus (44 patients in the elafibranor group and 22 in the placebo group), the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (−1.93 vs. −1.15; difference, −0.78; 95% CI, −1.99 to 0.42; P=0.20).” (opens the source at this quote in a new tab)

Safety results

Selected adverse reactions during the double-blind period

Adverse reaction	Elafibranor	Placebo
Diarrhea, % (n)	“11% (12)”	“9% (5)”
Muscle pain, % (n)	“7% (8)”	“2% (1)”
Fracture, % (n)	“6% (7)”	“0”

Adverse events more frequent with elafibranor than placebo

“Adverse events that occurred more frequently with elafibranor than with placebo included abdominal pain, diarrhea, nausea, and vomiting.” (opens the source at this quote in a new tab)

Study limitations

Summary

This comparator trial does not provide a head-to-head estimate against saroglitazar. Its primary endpoint was biochemical response at 52 weeks. The population was 96% female, and eligibility excluded decompensated cirrhosis, limiting extrapolation to that population.