Trial Outcomes & Findings for A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3) (NCT NCT04771273)

Last Updated: 2024-12-03

Results Overview

Percentage of patients who had an improvement from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment is reported. Percentages were rounded to one decimal place. Improvement in histological findings was defined as a composite of improvement in NASH and no worsening of fibrosis. Improvement in non-alcoholic steatohepatitis (NASH) was defined as decrease of at least 2 points in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning. The NAS represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease. The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease. Patients without post-baseline data were considered non-responders.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

295 participants

Primary outcome timeframe

At baseline and at 48 weeks.

Results posted on

2024-12-03

Participant Flow

This was a 48 weeks, multi-centre, randomised, dose-ranging, double-blind, placebo-controlled, parallel-group trial to evaluate efficacy, safety and tolerability of multiple subcutaneous (s.c.) doses of survodutide (BI 456906) in patients with non-alcoholic steatohepatitis (NASH). Main parameters for inclusion of patients and for evaluation of treatment response were based on the histological evaluation from the liver biopsy and non-invasive imaging modalities.

All subjects were screened for eligibility prior to participation in the trial. Patients who met the eligibility criteria at an initial screening visit had a second screening visit for biopsy to confirm their eligibility, if no sufficient material from a historical biopsy within the 6 months prior to randomisation was available.

Participant milestones

Participant milestones
Measure	Survodutide 2.4 mg - Planned Maintenance Treatment Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 2.4 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Survodutide 4.8 mg - Planned Maintenance Treatment Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 4.8 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Survodutide 6.0 mg - Planned Maintenance Treatment Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 6.0 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Placebo - Planned Maintenance Treatment Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were administered once weekly, subcutaneously a solution for injection of placebo matching survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period).
Dose Escalation Period STARTED	73	73	75	74
Dose Escalation Period Treated With Trial Medication	73	72	74	74
Dose Escalation Period COMPLETED	62	63	57	68
Dose Escalation Period NOT COMPLETED	11	10	18	6
Maintenance Period STARTED	62	63	57	68
Maintenance Period COMPLETED	53	55	49	64
Maintenance Period NOT COMPLETED	9	8	8	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Survodutide 2.4 mg - Planned Maintenance Treatment Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 2.4 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Survodutide 4.8 mg - Planned Maintenance Treatment Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 4.8 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Survodutide 6.0 mg - Planned Maintenance Treatment Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 6.0 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Placebo - Planned Maintenance Treatment Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were administered once weekly, subcutaneously a solution for injection of placebo matching survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period).
Dose Escalation Period Not treated with trial medication	0	1	1	0
Dose Escalation Period Other reasons than listed	2	0	2	1
Dose Escalation Period Protocol Violation	0	0	3	1
Dose Escalation Period Burden of study procedures	1	0	0	0
Dose Escalation Period Change of residence	0	0	0	1
Dose Escalation Period Perceived lack of efficacy	0	0	0	1
Dose Escalation Period Adverse Event	8	9	12	2
Maintenance Period Other than listed	4	2	0	3
Maintenance Period Burden of study procedures	1	0	0	0
Maintenance Period Change of residence	0	1	3	0
Maintenance Period Perceived lack of efficacy	0	0	0	1
Maintenance Period Adverse Event	4	5	5	0

Baseline Characteristics

A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Survodutide 2.4 mg - Planned Maintenance Treatment n=73 Participants Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 2.4 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Survodutide 4.8 mg - Planned Maintenance Treatment n=72 Participants Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 4.8 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Survodutide 6.0 mg - Planned Maintenance Treatment n=74 Participants Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were to be administered once weekly, subcutaneously a solution for injection of survodutide at a starting dose of 0.3 milligrams (mg) followed by a dose escalation up to the maintenance dose of 6.0 mg of survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period). Participants not tolerating the assigned dose due to gastrointestinal adverse events had the option of a dose adjustment which could lead to a maintenance dose lower than the dose the patient was randomized to.	Placebo - Planned Maintenance Treatment n=74 Participants Patients with non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 and fibrosis stage 1-3 (F1-F3). were administered once weekly, subcutaneously a solution for injection of placebo matching survodutide. The total treatment duration was 48 weeks (consisting of up to 24 weeks dose escalation period and at least 24 weeks maintenance period).	Total n=293 Participants Total of all reporting groups
Number of patients in each category of NAS score 5	27 Participants n=5 Participants	21 Participants n=7 Participants	17 Participants n=5 Participants	28 Participants n=4 Participants	93 Participants n=21 Participants
Number of patients in each category of NAS score 6	17 Participants n=5 Participants	22 Participants n=7 Participants	26 Participants n=5 Participants	8 Participants n=4 Participants	73 Participants n=21 Participants
Age, Continuous	49.6 years STANDARD_DEVIATION 13.7 • n=5 Participants	50.2 years STANDARD_DEVIATION 12.9 • n=7 Participants	50.4 years STANDARD_DEVIATION 13.1 • n=5 Participants	53.0 years STANDARD_DEVIATION 11.5 • n=4 Participants	50.8 years STANDARD_DEVIATION 12.8 • n=21 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	34 Participants n=7 Participants	41 Participants n=5 Participants	44 Participants n=4 Participants	155 Participants n=21 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	38 Participants n=7 Participants	33 Participants n=5 Participants	30 Participants n=4 Participants	138 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	19 Participants n=7 Participants	26 Participants n=5 Participants	22 Participants n=4 Participants	81 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants	53 Participants n=7 Participants	48 Participants n=5 Participants	52 Participants n=4 Participants	212 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	24 Participants n=5 Participants	22 Participants n=7 Participants	17 Participants n=5 Participants	17 Participants n=4 Participants	80 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	47 Participants n=7 Participants	56 Participants n=5 Participants	56 Participants n=4 Participants	205 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
NAS score at baseline	5.2 score on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	5.3 score on a scale STANDARD_DEVIATION 1.1 • n=7 Participants	5.1 score on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	5.2 score on a scale STANDARD_DEVIATION 1.1 • n=4 Participants	5.2 score on a scale STANDARD_DEVIATION 1.0 • n=21 Participants
Number of participants at each category of liver fibrosis stage at baseline Stage 1A	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	8 Participants n=21 Participants
Number of participants at each category of liver fibrosis stage at baseline Stage 1B	17 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants	9 Participants n=4 Participants	47 Participants n=21 Participants
Number of participants at each category of liver fibrosis stage at baseline Stage 1C	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	15 Participants n=21 Participants
Number of participants at each category of liver fibrosis stage at baseline Stage 2	30 Participants n=5 Participants	36 Participants n=7 Participants	24 Participants n=5 Participants	30 Participants n=4 Participants	120 Participants n=21 Participants
Number of participants at each category of liver fibrosis stage at baseline Stage 3	23 Participants n=5 Participants	23 Participants n=7 Participants	27 Participants n=5 Participants	30 Participants n=4 Participants	103 Participants n=21 Participants
Number of participants in each category of diabetes at baseline No	44 Participants n=5 Participants	43 Participants n=7 Participants	44 Participants n=5 Participants	45 Participants n=4 Participants	176 Participants n=21 Participants
Number of participants in each category of diabetes at baseline Yes	29 Participants n=5 Participants	29 Participants n=7 Participants	30 Participants n=5 Participants	29 Participants n=4 Participants	117 Participants n=21 Participants
Number of patients in each category of NAS score 0	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Number of patients in each category of NAS score 1	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Number of patients in each category of NAS score 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Number of patients in each category of NAS score 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Number of patients in each category of NAS score 4	21 Participants n=5 Participants	20 Participants n=7 Participants	26 Participants n=5 Participants	22 Participants n=4 Participants	89 Participants n=21 Participants
Number of patients in each category of NAS score 7	8 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	16 Participants n=4 Participants	37 Participants n=21 Participants
Number of patients in each category of NAS score 8	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (steatosis and lobular inflammation) Steatosis · 0	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (steatosis and lobular inflammation) Steatosis · 1	6 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (steatosis and lobular inflammation) Steatosis · 2	38 Participants n=5 Participants	38 Participants n=7 Participants	49 Participants n=5 Participants	43 Participants n=4 Participants	168 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (steatosis and lobular inflammation) Steatosis · 3	29 Participants n=5 Participants	34 Participants n=7 Participants	24 Participants n=5 Participants	28 Participants n=4 Participants	115 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (steatosis and lobular inflammation) Lobular inflammation · 0	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (steatosis and lobular inflammation) Lobular inflammation · 1	32 Participants n=5 Participants	31 Participants n=7 Participants	36 Participants n=5 Participants	37 Participants n=4 Participants	136 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (steatosis and lobular inflammation) Lobular inflammation · 2	38 Participants n=5 Participants	40 Participants n=7 Participants	36 Participants n=5 Participants	32 Participants n=4 Participants	146 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (steatosis and lobular inflammation) Lobular inflammation · 3	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	11 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (ballooning) 0	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (ballooning) 1	55 Participants n=5 Participants	55 Participants n=7 Participants	53 Participants n=5 Participants	49 Participants n=4 Participants	212 Participants n=21 Participants
Number of patients in each category of the NAS sub-scores (ballooning) 2	18 Participants n=5 Participants	17 Participants n=7 Participants	21 Participants n=5 Participants	25 Participants n=4 Participants	81 Participants n=21 Participants

PRIMARY outcome

Timeframe: At baseline and at 48 weeks.

Population: Treated set - actual maintenance treatment. Patients are analyzed according to the actual treatment they received at the start of the dose maintenance period (for patients who reached the maintenance period) or the next maintenance dose up from the dose at treatment discontinuation (for patients who discontinued treatment prior to the maintenance period).

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=93 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=69 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=52 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=79 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Actual Maintenance Treatment	38.7 Percentage of participants	63.8 Percentage of participants	55.8 Percentage of participants	15.2 Percentage of participants

PRIMARY outcome

Timeframe: At baseline and after 48 weeks of treatment.

Population: Treated set - planned maintenance treatment: included all patients that were administered survodutide or placebo matching survodutide. Patients are analyzed for this endpoint according to the planned treatment (planned maintenance dose strength) they were assigned at randomisation even if patients did not reach the maintenance period at all, and therefore did not "settle" on any maintenance dose.

Percentage of patients who had an improvement from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment is reported. Percentages were rounded to one decimal place. Improvement in histological findings was defined as a composite of improvement in non-alcoholic steatohepatitis (NASH) and no worsening of fibrosis. Improvement in NASH was defined as decrease of at least 2 points in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning. The NAS represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease. The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease. Patients without post-baseline data were considered non-responders.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=73 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=72 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=74 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=74 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Planned Maintenance Treatment	46.6 percentage of participants	62.5 percentage of participants	43.2 percentage of participants	13.5 percentage of participants

SECONDARY outcome

Timeframe: At baseline and after 48 weeks.

Percentage of participants with improvement in liver fat content is reported. Improvement in liver fat content was defined as percentage reduction from baseline of ≥30% in liver fat content after 48 weeks of treatment compared to baseline. Percentages were rounded to one decimal place. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Patients without post-baseline values were imputed as non-responders.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=93 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=69 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=52 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=79 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Actual Maintenance Treatment	50.5 Percentage of participants	66.7 Percentage of participants	76.9 Percentage of participants	16.5 Percentage of participants

SECONDARY outcome

Timeframe: At baseline and at 48 weeks.

Percentage of participants with improvement in liver fat content is reported. Improvement in liver fat content was defined as percentage reduction from baseline of ≥30% in liver fat content after 48 weeks of treatment compared to baseline. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Patients without post-baseline values were imputed as non-responders.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=73 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=72 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=74 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=74 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Planned Maintenance Treatment	63.0 Percentage of participants	66.7 Percentage of participants	56.8 Percentage of participants	13.5 Percentage of participants

SECONDARY outcome

Timeframe: MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.

Absolute change of liver fat content (percentage \[%\]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=68 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=60 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=51 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=73 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment	-10.48 percentage of liver fat content Interval -11.92 to -9.04	-12.80 percentage of liver fat content Interval -14.32 to -11.28	-12.96 percentage of liver fat content Interval -14.62 to -11.3	-1.89 percentage of liver fat content Interval -3.26 to -0.51

SECONDARY outcome

Timeframe: MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.

Population: Treated set - planned maintenance treatment. Patients are analyzed for this endpoint according to the planned treatment (planned maintenance dose strength) they were assigned at randomisation even if patients did not reach the maintenance period at all, and therefore did not "settle" on any maintenance dose. The reported number of participants analyzed reflects the number of participants in the analysis model.

Absolute change of liver fat content from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=61 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=64 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=58 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=69 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment	-10.73 percentage of liver fat content Interval -12.25 to -9.22	-12.40 percentage of liver fat content Interval -13.9 to -10.91	-12.48 percentage of liver fat content Interval -14.06 to -10.89	-1.61 percentage of liver fat content Interval -3.04 to -0.19

SECONDARY outcome

Timeframe: MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.

Percent change of liver fat content (percentage \[%\]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=68 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=60 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=51 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=73 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment	-50.92 percent change of liver fat content Interval -58.05 to -43.8	-62.79 percent change of liver fat content Interval -70.26 to -55.32	-64.30 percent change of liver fat content Interval -72.48 to -56.12	-7.28 percent change of liver fat content Interval -14.06 to -0.5

SECONDARY outcome

Timeframe: MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.

Population: Treated set - planned maintenance treatment: all patients that administered survodutide or placebo matching survodutide. Patients are analyzed for this endpoint according to the planned treatment (planned maintenance dose strength) they were assigned at randomisation even if patients did not reach the maintenance period at all, and therefore did not "settle" on any maintenance dose. The reported number of participants analyzed reflects the number of participants in the analysis model.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=61 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=64 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=58 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=69 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment	-52.20 percent change of liver fat content Interval -59.66 to -44.75	-60.82 percent change of liver fat content Interval -68.16 to -53.48	-61.97 percent change of liver fat content Interval -69.78 to -54.16	-5.71 percent change of liver fat content Interval -12.7 to 1.28

SECONDARY outcome

Timeframe: At baseline and after 48 weeks of treatment.

Percentage of participants with improvement of liver fibrosis is reported. Improvement of fibrosis was defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy. The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease and the stages of fibrosis based on their location are the following: * 1A Zone 3, perisinusoidal, delicate; * 1B Zone 3, perisinusoidal, dense; * 1C Portal, periportal only; * 2 Zone 3, perisinusoidal + portal, periportal only; * 3 Bridging fibrosis; * 4 Cirrhosis. For analysis purposes no distinction was made between stages 1A, 1B and 1C.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=93 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=69 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=52 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=79 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment	30.1 Percentage of participants	34.8 Percentage of participants	44.2 Percentage of participants	21.5 Percentage of participants

SECONDARY outcome

Timeframe: At baseline and after 48 weeks of treatment.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=73 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=72 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=74 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=74 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment	34.2 Percentage of participants	36.1 Percentage of participants	33.8 Percentage of participants	21.6 Percentage of participants

SECONDARY outcome

Timeframe: At baseline and 48 weeks of treatment.

Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy is reported. The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=56 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=53 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=44 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=66 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment	-2.8 units on a scale Standard Deviation 1.8	-3.2 units on a scale Standard Deviation 1.8	-3.3 units on a scale Standard Deviation 2.0	-0.4 units on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: At baseline and 48 weeks of treatment.

Outcome measures

Outcome measures
Measure	Survodutide 2.4 mg - Actual Maintenance Treatment n=53 Participants This arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 4.8 mg - Actual Maintenance Treatment n=55 Participants This arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Survodutide 6.0 mg - Actual Maintenance Treatment n=48 Participants This arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.	Placebo - Actual Maintenance Treatment n=63 Participants This arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment	-2.8 units on a scale Standard Deviation 1.8	-3.2 units on a scale Standard Deviation 1.8	-3.3 units on a scale Standard Deviation 1.9	-0.2 units on a scale Standard Deviation 1.5

Adverse Events

Survodutide 2.4 mg - Actual Maintenance Treatment

Serious events: 5 serious events

Other events: 85 other events

Deaths: 0 deaths

Survodutide 4.8 mg - Actual Maintenance Treatment

Serious events: 7 serious events

Other events: 60 other events

Deaths: 0 deaths

Survodutide 6.0 mg - Actual Maintenance Treatment

Serious events: 5 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo - Actual Maintenance Treatment

Serious events: 5 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

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