A Study of MK-3655 in Individuals With Pre-cirrhotic Nona... | NCT04583423

NCT04583423

ID	Type	Description
MK-3655-001	Other Identifier	Merck Protocol Number
jRCT2051200083	Registry Identifier	jRCT
2019-003048-63	EudraCT Number

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MK-3655 50 mg	Experimental	Following a 2-week placebo run-in, participants will receive MK-3655 50 mg by subcutaneous (SC) injection once every 4 weeks (Q4W) for 52 weeks.	Drug: MK-3655
MK-3655 100 mg	Experimental	Following a 2-week placebo run-in, participants will receive MK-3655 100 mg by SC injection Q4W for 52 weeks.	Drug: MK-3655
MK-3655 300 mg	Experimental	Following a 2-week placebo run-in, participants will receive MK-3655 300 mg by SC injection Q4W for 52 weeks.	Drug: MK-3655
Placebo	Placebo Comparator	Following a 2-week placebo run-in, participants will receive Placebo by SC injection Q4W for 52 weeks.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
MK-3655	Drug	MK-3655 50, 100 or 300 dose for injection	MK-3655 100 mg MK-3655 300 mg MK-3655 50 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 52 Weeks	The NASH Clinical Research Network (CRN) scoring system evaluated by Blinded Independent Central Review (BICR) was used to assess treatment response. The NASH CRN scoring scales were: lobular inflammation score (0-3); hepatocyte ballooning score (0-2); steatosis score (0-3); and fibrosis score (0-4). NASH resolution was defined as a score of 0-1 for inflammation, 0 for ballooning, and any grade of steatosis.	Week 52
Percentage of Participants Who Experienced an Adverse Event (AE)	An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.	Up to 64 weeks
Percentage of Participants Discontinuing Study Medication Due to an AE	An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.	Up to 52 weeks

Secondary Outcomes

Measure	Description	Time Frame
Mean Percent Relative Reduction From Baseline in Liver Fat Content (LFC) After 24 Weeks	LFC % was measured by Magnetic Resonance Imaging-Estimated Proton Density Fat Fraction (MRI-PDFF) and evaluated by BICR. MRI-PDFF is a highly accurate noninvasive measure of the proportion of fat content of a tissue.	Baseline and Week 24

Eligibility Module

Name	Affiliation	Role
Medical Director, MD	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Adobe Clinical Research, LLC ( Site 2644)		Tucson	Arizona	85712	United States
Arizona Liver Health ( Site 9026)

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39984821	Result	Raji A, Gantz I, Crutchlow M, Flynn H, Xu L, Rodgers AJ, Krishnan R, Rizk ML, Hu S, Kaufman KD, Engel SS; MK-3655 P001 Study Group. Clinical Trial: A Phase 2b Study to Evaluate the Efficacy and Safety of MK-3655 in Individuals With Pre-Cirrhotic MASH. Aliment Pharmacol Ther. 2025 Apr;61(7):1152-1162. doi: 10.1111/apt.70038. Epub 2025 Feb 21.

Label	URL
Merck Clinical Trials Information	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by subcutaneous (SC) injection once every 4 weeks (Q4W) for 52 weeks.
FG001	MK-3655 100 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 24, 2022

Arm/Group Information

ID	Title	Description
BG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by SC injection Q4W for 52 weeks.
BG001	MK-3655 100 mg	Following a 2-week placebo run-in, participants received MK-3655 100 mg by SC injection Q4W for 52 weeks.
BG002	MK-3655 300 mg	Following a 2-week placebo run-in, participants received MK-3655 300 mg by SC injection Q4W for 52 weeks.
BG003	Placebo	Following a 2-week placebo run-in, participants received placebo by SC injection Q4W for 52 weeks.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00059.6± 8.9 BG00154.3± 12.3 BG00256.6± 11.3 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00025 BG00120 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00012 BG00113 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Baseline Fibrosis Stage

The NASH Clinical Research Network (CRN) scoring system assesses NASH activity and fibrosis stage based on the following scoring scales: lobular inflammation score (0-3); hepatocyte ballooning score (0-2); steatosis score (0-3); and fibrosis score (0-4). The Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) was calculated as the unweighted sum of the scores for inflammation, ballooning, and steatosis and ranged from 0-8 (highest activity).

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Stage 2	BG00021 BG001

Percent Liver Fat Content

Assessed via Magnetic Resonance Imaging-Estimated Proton Density Fat Fraction (MRI-PDFF), a highly accurate noninvasive measure of the proportion of fat content of a tissue

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<20%	BG00030 BG00123

Type 2 Diabetes Mellitus (T2DM)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG00022 BG00125 BG002

Region

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Japan	BG00011 BG00112 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 52 Weeks

The NASH Clinical Research Network (CRN) scoring system evaluated by Blinded Independent Central Review (BICR) was used to assess treatment response. The NASH CRN scoring scales were: lobular inflammation score (0-3); hepatocyte ballooning score (0-2); steatosis score (0-3); and fibrosis score (0-4). NASH resolution was defined as a score of 0-1 for inflammation, 0 for ballooning, and any grade of steatosis.

Full Analysis Set (FAS) population, which consisted of all randomized participants who had at least 1 injection of study intervention and had at least 1 assessment

Posted

Number

Percentage of Participants

Week 52

ID	Title	Description
OG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by SC injection Q4W for 52 weeks.
OG001	MK-3655 100 mg	Following a 2-week placebo run-in, participants received MK-3655 100 mg by SC injection Q4W for 52 weeks.
OG002	MK-3655 300 mg	Following a 2-week placebo run-in, participants received MK-3655 300 mg by SC injection Q4W for 52 weeks.
OG003	Placebo	Following a 2-week placebo run-in, participants received placebo by SC injection Q4W for 52 weeks.

Units	Counts
Participants	OG00018 OG00121 OG00217 OG003

Title

Denominators

Categories

Title	Measurements
	OG00016.7 OG00114.3 OG00217.6 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003		Miettinen and Nurminen's method	Stratified by concurrent diagnosis of T2DM at the time of randomization and fibrosis score and using Cochran-Mantel-Haenszel weighting scheme	0.3504		Difference in Percentages	10.4			2-Sided	95	-13.4	35.1			Difference=% 50-mg MK-3655 minus % placebo		Other
OG001

Primary

Percentage of Participants Who Experienced an Adverse Event (AE)

An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.

All Participants as Treated (APaT) population, which included all randomized participants who received at least 1 injection of study intervention

Posted

Number

Percentage of Participants

Up to 64 weeks

ID	Title	Description
OG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by SC injection Q4W for 52 weeks.
OG001	MK-3655 100 mg	Following a 2-week placebo run-in, participants received MK-3655 100 mg by SC injection Q4W for 52 weeks.
OG002	MK-3655 300 mg	Following a 2-week placebo run-in, participants received MK-3655 300 mg by SC injection Q4W for 52 weeks.
OG003	Placebo

Primary

Percentage of Participants Discontinuing Study Medication Due to an AE

APaT population, which included all randomized participants who received at least 1 injection of study intervention

Posted

Number

Percentage of Participants

Up to 52 weeks

ID	Title	Description
OG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by SC injection Q4W for 52 weeks.
OG001	MK-3655 100 mg	Following a 2-week placebo run-in, participants received MK-3655 100 mg by SC injection Q4W for 52 weeks.
OG002	MK-3655 300 mg	Following a 2-week placebo run-in, participants received MK-3655 300 mg by SC injection Q4W for 52 weeks.
OG003	Placebo

Secondary

Mean Percent Relative Reduction From Baseline in Liver Fat Content (LFC) After 24 Weeks

LFC % was measured by Magnetic Resonance Imaging-Estimated Proton Density Fat Fraction (MRI-PDFF) and evaluated by BICR. MRI-PDFF is a highly accurate noninvasive measure of the proportion of fat content of a tissue.

FAS population, which consisted of all randomized participants who had at least 1 injection of study intervention and had at least 1 assessment

Posted

Least Squares Mean

95% Confidence Interval

Percent Change

Baseline and Week 24

ID	Title	Description
OG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by SC injection Q4W for 52 weeks.
OG001	MK-3655 100 mg	Following a 2-week placebo run-in, participants received MK-3655 100 mg by SC injection Q4W for 52 weeks.
OG002	MK-3655 300 mg	Following a 2-week placebo run-in, participants received MK-3655 300 mg by SC injection Q4W for 52 weeks.
OG003	Placebo

Secondary

Percentage of Participants With ≥1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis Assessed With the NASH CRN Scoring System After 52 Weeks

Participants were evaluated with the NASH CRN scoring system with BICR with ≥1 stage improvement in fibrosis without worsening of steatohepatitis defined as no increase in the ballooning, inflammation, or steatosis scores.

FAS population, which consisted of all randomized participants who had at least 1 injection of study intervention and had at least 1 assessment

Posted

Number

Percentage of Participants

Week 52

ID	Title	Description
OG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by SC injection Q4W for 52 weeks.
OG001	MK-3655 100 mg	Following a 2-week placebo run-in, participants received MK-3655 100 mg by SC injection Q4W for 52 weeks.
OG002	MK-3655 300 mg	Following a 2-week placebo run-in, participants received MK-3655 300 mg by SC injection Q4W for 52 weeks.
OG003	Placebo

Secondary

Percentage of Participants With ≥2 Point Improvement in NAS With ≥1 Point Improvement in Inflammation or Ballooning Without Worsening of Fbrosis by Histology (Evaluated by BICR) After 52 Weeks

Participants with ≥2 point improvement in the NAS with ≥1 point improvement in inflammation or ballooning without worsening of fibrosis were assessed with the NASH CRN scoring system (evaluated by BICR). The NAS was calculated as the unweighted sum of the scores and ranges from 0-8 (highest activity).

FAS population, which consisted of all randomized participants who had at least 1 injection of study intervention and had at least 1 assessment

Posted

Number

Percentage of Participants

Week 52

ID	Title	Description
OG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by SC injection Q4W for 52 weeks.
OG001	MK-3655 100 mg	Following a 2-week placebo run-in, participants received MK-3655 100 mg by SC injection Q4W for 52 weeks.
OG002	MK-3655 300 mg	Following a 2-week placebo run-in, participants received MK-3655 300 mg by SC injection Q4W for 52 weeks.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MK-3655 50 mg	Following a 2-week placebo run-in, participants received MK-3655 50 mg by SC injection Q4W for 52 weeks.	45	1	45	19	45
EG001	MK-3655 100 mg	Following a 2-week placebo run-in, participants received MK-3655 100 mg by SC injection Q4W for 52 weeks.	48	1	47	26	47
EG002	MK-3655 300 mg	Following a 2-week placebo run-in, participants received MK-3655 300 mg by SC injection Q4W for 52 weeks.	46	1	46	27	46
EG003	Placebo	Following a 2-week placebo run-in, participants received placebo by SC injection Q4W for 52 weeks.	44	8	44	21	44

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Sinoatrial block	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG0031 events1 affected44 at risk
Cataract	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0021 events1 affected46 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0021 events1 affected46 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
Forearm fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003
Calculus bladder	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected47 at risk EG0020 events0 affected46 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected47 at risk EG0020 events0 affected46 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected47 at risk EG0023 events3 affected46 at risk EG0032 events2 affected44 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0005 events4 affected45 at risk EG0017 events7 affected47 at risk EG0025 events5 affected46 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected45 at risk EG0013 events3 affected47 at risk EG0022 events1 affected46 at risk EG003
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0004 events2 affected45 at risk EG0012 events2 affected47 at risk EG0022 events2 affected46 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected45 at risk EG00111 events9 affected47 at risk EG0026 events5 affected46 at risk EG003
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected45 at risk EG0013 events3 affected47 at risk EG0020 events0 affected46 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected45 at risk EG0016 events4 affected47 at risk EG0022 events2 affected46 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected45 at risk EG0012 events2 affected47 at risk EG0021 events1 affected46 at risk EG003
Weight increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected47 at risk EG0023 events3 affected46 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected45 at risk EG0011 events1 affected47 at risk EG0020 events0 affected46 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected45 at risk EG0015 events5 affected47 at risk EG0024 events4 affected46 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected47 at risk EG00211 events7 affected46 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 events1 affected45 at risk EG0013 events3 affected47 at risk EG0026 events4 affected46 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected47 at risk EG0021 events1 affected46 at risk EG003
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected45 at risk EG0011 events1 affected47 at risk EG0026 events5 affected46 at risk EG003
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected45 at risk EG0018 events6 affected47 at risk EG0027 events6 affected46 at risk EG003

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases