parallel randomized trial

NCT03987451

Investigation of Efficacy and Safety of Semaglutide s.c. Once-weekly Versus Placebo in Subjects With Non-alcoholic Steatohepatitis and Compensated Liver Cirrhosis

Metabolic dysfunction associated steatotic liver disease or steatohepatitis NCT03987451S001764

Design

Randomized: 71
Start year: 2019
Treatment: 48 weeks, follow-up 55 weeks
Countries: multinational (38 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 to 75; biopsy NASH with F4 compensated cirrhosis; NAS 3 or more; BMI 27 or more

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: nonresponder imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 2.4 mg subcutaneous once weekly Semaglutide 2.4 mg once weekly	lifestyle: standard	47	47
A2	Placebo Placebo	lifestyle: standard	24	24

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Semaglutide 2.4 mg subcutaneous once weekly A1	Placebo A2
age	mean (years)	59.9	58.7
age	sd (years)	7.1	9.7
asian	n	1	0
asian	percent	2
black	n	0	2
black	percent		8
bmi	mean (kg/m2)	34.6	35.5
bmi	sd (kg/m2)	5.9	6.0
female	n	31	18
female	percent	66	75
hba1c	mean (percent)	7.1	7.2
hba1c	sd (percent)	1.3	1.2
other race american indian alaska native	n	1	0
other race american indian alaska native	percent	2
other race other	n	1	0
other race other	percent	2
sbp	mean (mmHg)	132.6	135.8
sbp	sd (mmHg)	13.7	14.7
weight	mean (kg)	95.2	98.6
weight	sd (kg)	18.7	22.2
white	n	41	21
white	percent	87	88

Analyses this trial contributes to

Results

51 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

HbA1c change (3 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
48	A1 vs A2	md	-1.63 percent		-2.20 to -1.06		treatment policy; full analysis; diabetes:t2d; R0017043:Results
48	A1	change	-1.4 percent	1.1		34	treatment policy; full analysis; diabetes:t2d; registry:outcomes
48	A2	change	0.2 percent	1.1		18	treatment policy; full analysis; diabetes:t2d; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (4 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	12 / 35	while on treatment; safety; diabetes:t2d; R0017043:Results
A1	events	1 / 35	while on treatment; safety; diabetes:t2d; R0017043:Results
A2	events	5 / 18	while on treatment; safety; diabetes:t2d; R0017043:Results
A2	events	0 / 18	while on treatment; safety; diabetes:t2d; R0017043:Results

Percent body weight change (3 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
48	A1	percent change	-8.83 percent	7.44		47	treatment policy; full analysis; registry:outcomes
48	A1 vs A2	md	-8.75 percent		-12.41 to -5.09		treatment policy; full analysis; R0017043:Results
48	A2	percent change	-0.09 percent	7.44		24	treatment policy; full analysis; registry:outcomes

Weight loss of 5 percent or more (4 lines; O11A)

Week	Arm	Statistic	Estimate	Events / N	Detail
48	A1	responders		29 / 47	not stated; full analysis; R0017043:Results
48	A1	responders	62.0	47	treatment policy; full analysis; registry:outcomes
48	A2	responders		6 / 24	not stated; full analysis; R0017043:Results
48	A2	responders	25.4	24	treatment policy; full analysis; registry:outcomes

Weight loss of 10 percent or more (3 lines; O11B)

Week	Arm	Statistic	Estimate	Events / N	Detail
48	A1	responders		19 / 47	not stated; full analysis; R0017043:Results
48	A1	responders	40.5	47	treatment policy; full analysis; registry:outcomes
48	A2	responders		0 / 24	not stated; full analysis; R0017043:Results

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 47	not stated; safety; R0017043:Table 2
	A2	events				0 / 24	not stated; safety; R0017043:Table 2

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	6 / 47	treatment policy; safety; R0017043:Table 2
A1	events	6 / 47	while on treatment; safety; R0017043:Table 2
A2	events	2 / 24	treatment policy; safety; R0017043:Table 2
A2	events	2 / 24	while on treatment; safety; R0017043:Table 2

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 47	while on treatment; safety; R0017043:Table 2
A1	events	3 / 47	while on treatment; safety; R0017043:Table 2
A2	events	0 / 24	while on treatment; safety; R0017043:Table 2
A2	events	0 / 24	while on treatment; safety; R0017043:Table 2

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				21 / 47	while on treatment; safety; R0017043:Table 2
	A2	events				4 / 24	while on treatment; safety; R0017043:Table 2

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				8 / 47	while on treatment; safety; R0017043:Table 2
	A2	events				0 / 24	while on treatment; safety; R0017043:Table 2

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 47	while on treatment; safety; R0017043:Table 2
	A2	events				2 / 24	while on treatment; safety; R0017043:Table 2

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				3 / 47	not stated; safety; registry:adverse_events
	A2	events				2 / 24	not stated; safety; registry:adverse_events

Discontinuation due to gastrointestinal adverse events (2 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 47	while on treatment; safety; R0017043:Results
	A2	events				0 / 24	while on treatment; safety; R0017043:Results

Gallbladder and biliary disease (2 lines; O28)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 47	not stated; safety; Cholelithiasis; registry:adverse_events
	A2	events				0 / 24	not stated; safety; Cholelithiasis; registry:adverse_events

Suicidal ideation or behavior (2 lines; O35A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 47	not stated; safety; Suicide attempt; registry:adverse_events
	A2	events				1 / 24	not stated; safety; Suicide attempt; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 47	not stated; safety; R0017043:Results
	A2	events				0 / 24	not stated; safety; R0017043:Results

Gastroparesis (2 lines; O37A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 47	not stated; safety; Impaired gastric emptying; registry:adverse_events
	A2	events				0 / 24	not stated; safety; Impaired gastric emptying; registry:adverse_events

Resolution of steatohepatitis without worsening of fibrosis (3 lines; O60)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
48	A1	responders			16 / 47	treatment policy; full analysis; R0017043:Results
48	A1 vs A2	or	1.97	0.56 to 7.91		treatment policy; full analysis; R0017043:Results
48	A2	responders			5 / 24	treatment policy; full analysis; R0017043:Results

Fibrosis improvement without worsening of steatohepatitis (3 lines; O61)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
48	A1	responders			5 / 47	treatment policy; full analysis; R0017043:Results
48	A1 vs A2	or	0.28	0.06 to 1.24		treatment policy; full analysis; R0017043:Results
48	A2	responders			7 / 24	treatment policy; full analysis; R0017043:Results