Evaluation of Efficacy, Safety and Tolerability of Aldafe... | NCT03912532

NCT03912532

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions 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
NGM282 Dose 1	Experimental	Administered by subcutaneous injection	Biological: NGM282
NGM282 Dose 2	Experimental	Administered by subcutaneous injection	Biological: NGM282
NGM282 Dose 3	Experimental	Administered by subcutaneous injection	Biological: NGM282
Placebo	Placebo Comparator	Administered by subcutaneous injection	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
NGM282	Biological	NGM282	NGM282 Dose 1 NGM282 Dose 2 NGM282 Dose 3

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Liver Fibrosis Response After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis	Liver biopsies were collected at baseline and Week 24 and read by a central pathologist using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) criteria. Fibrosis stages of F0, F1, F2, F3 and F4 are defined by NASH CRN criteria with F0 (minimal score) indicating no fibrosis and F4 (maximal score) indicating liver cirrhosis. Liver fibrosis response was defined as an improvement in liver fibrosis >=1 stage with no worsening of steatohepatitis on liver biopsy at Week 24 compared with baseline.	Baseline up to Week 24
Number of Participants With Treatment-emergent Adverse Events After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis	Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that commenced on or after the date and time of first study drug administration.	Baseline up to Week 24

Secondary Outcomes

Measure	Description	Time Frame
Mean Percentage of Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis	Mean percentage of liver fat content was assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF).	Baseline, Week 12, Week 24, and Week 30
Change From Baseline in Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
NGM Study Director	NGM Biopharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
NGM Clinical Study Site		Chandler	Arizona	85224	United States
NGM Clinical Study Site 814

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35325622	Derived	Harrison SA, Abdelmalek MF, Neff G, Gunn N, Guy CD, Alkhouri N, Bashir MR, Freilich B, Kohli A, Khazanchi A, Sheikh MY, Leibowitz M, Rinella ME, Siddiqui MS, Kipnes M, Moussa SE, Younes ZH, Bansal M, Baum SJ, Borg B, Ruane PJ, Thuluvath PJ, Gottwald M, Khan M, Chen C, Melchor-Khan L, Chang W, DePaoli AM, Ling L, Lieu HD. Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2022 Jul;7(7):603-616. doi: 10.1016/S2468-1253(22)00017-6. Epub 2022 Mar 21.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Aldafermin 0.3 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 0.3 mg.
FG001	Aldafermin 1.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 1.0 mg.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 15, 2020	Mar 7, 2025

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Baseline characteristics were assessed in the Intent-to-Treat Analysis Set.

Arm/Group Information

ID	Title	Description
BG000	Aldafermin 0.3 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 0.3 mg.
BG001	Aldafermin 1.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 1.0 mg.
BG002	Aldafermin 3.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 3.0 mg.
BG003	Placebo	Participants who were randomized to receive a single subcutaneous injection of placebo.
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, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0011 BG0020 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00054.3± 11.2 BG00149.8± 13.2 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00028 BG00129 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG00040 BG00138 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

Liver Fibrosis Response After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis

Liver biopsies were collected at baseline and Week 24 and read by a central pathologist using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) criteria. Fibrosis stages of F0, F1, F2, F3 and F4 are defined by NASH CRN criteria with F0 (minimal score) indicating no fibrosis and F4 (maximal score) indicating liver cirrhosis. Liver fibrosis response was defined as an improvement in liver fibrosis >=1 stage with no worsening of steatohepatitis on liver biopsy at Week 24 compared with baseline.

Liver fibrosis response was assessed in the Intent-to-Treat Analysis Set.

Posted

Mean

Standard Error

score on a scale

Baseline up to Week 24

ID	Title	Description
OG000	Aldafermin 0.3 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 0.3 mg.
OG001	Aldafermin 1.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 1.0 mg.
OG002	Aldafermin 3.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 3.0 mg.
OG003	Placebo	Participants who were randomized to receive a single subcutaneous injection of placebo.

Units	Counts
Participants	OG00043 OG00142 OG00243 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.24± 0.04 OG0010.25± 0.04 OG0020.27± 0.07 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 OG001 OG002 OG003		Multiple comparison procedure step		0.5534														Other	The Multiple Comparison Procedure-Modelling (MCP-Mod) is a 2-stage procedure in which dose-response models are selected at the design stage. These candidate models are used for both dose-response testing (MCP step) and estimation (Mod step). The dose-response testing is performed using a multiple comparison method to account for the multiplicity issue associated with the multiple candidate models. Missing responses were imputed using multiple imputation under the assumption of missing at random.

Primary

Number of Participants With Treatment-emergent Adverse Events After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis

Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that commenced on or after the date and time of first study drug administration.

TEAEs were assessed in the Safety Analysis Set.

Posted

Count of Participants

Participants

Baseline up to Week 24

ID	Title	Description
OG000	Aldafermin 0.3 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 0.3 mg.
OG001	Aldafermin 1.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 1.0 mg.
OG002	Aldafermin 3.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 3.0 mg.
OG003	Placebo	Participants who were randomized to receive a single subcutaneous injection of placebo.

Secondary

Mean Percentage of Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis

Mean percentage of liver fat content was assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF).

Mean change in liver fat content was assessed in the Intent-to-Treat Analysis Set.

Posted

Mean

Standard Deviation

percentage of liver fat content

Baseline, Week 12, Week 24, and Week 30

ID	Title	Description
OG000	Aldafermin 0.3 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 0.3 mg.
OG001	Aldafermin 1.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 1.0 mg.
OG002	Aldafermin 3.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 3.0 mg.
OG003	Placebo	Participants who were randomized to receive a single subcutaneous injection of placebo.

Secondary

Change From Baseline in Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis

Change from baseline in liver fat content was assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF). Negative values indicate an improvement in liver fat content.

Mean change from baseline in liver fat content was assessed in the Intent-to-Treat Analysis Set.

Posted

Mean

Standard Error

percentage of liver fat content

Baseline to Week 12, Week 24, and Week 30

ID	Title	Description
OG000	Aldafermin 0.3 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 0.3 mg.
OG001	Aldafermin 1.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 1.0 mg.
OG002	Aldafermin 3.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 3.0 mg.
OG003	Placebo	Participants who were randomized to receive a single subcutaneous injection of placebo.

Secondary

Number of Participants With Liver Fat Normalization and Response in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis

Liver fat normalization (LFC; defined as <5%) and response (LFC decrease >=5% from baseline and LFC relative decrease >=30% from baseline) were assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF). The responders were defined as participants with either normalization (<5%) or response (decrease from baseline >=5% or relative decrease from baseline >=30%).

Liver fat content normalization and response were assessed in participants with available data in the Intent-to-Treat Analysis Set.

Posted

Count of Participants

Participants

Baseline to Week 12, Week 24 and Week 30

ID	Title	Description
OG000	Aldafermin 0.3 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 0.3 mg.
OG001	Aldafermin 1.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 1.0 mg.
OG002	Aldafermin 3.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 3.0 mg.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Aldafermin 0.3 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 0.3 mg.	0	43	1	43	30	43
EG001	Aldafermin 1.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 1.0 mg.	1	41	4	41	34	41
EG002	Aldafermin 3.0 mg	Participants who were randomized to receive a single subcutaneous injection of aldafermin 3.0 mg.	0	43	1	43	38	43
EG003	Placebo	Participants who were randomized to receive a single subcutaneous injection of placebo.	0	43	3	43	36	43

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 affected43 at risk EG0010 affected41 at risk EG0020 affected43 at risk EG0030 affected43 at risk
Suicide attempt	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0011 affected41 at risk EG0020 affected43 at risk EG003
Cardiac hypertrophy	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0011 affected41 at risk EG0020 affected43 at risk EG003
Obesity	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0011 affected41 at risk EG0020 affected43 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0011 affected41 at risk EG0020 affected43 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0011 affected41 at risk EG0020 affected43 at risk EG003
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0010 affected41 at risk EG0021 affected43 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0010 affected41 at risk EG0020 affected43 at risk EG003
Bronchogenic cyst	Congenital, familial and genetic disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0010 affected41 at risk EG0020 affected43 at risk EG003
Endometrial adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0010 affected41 at risk EG0020 affected43 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected43 at risk EG0012 affected41 at risk EG0024 affected43 at risk EG0031 affected43 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected43 at risk EG0013 affected41 at risk EG0023 affected43 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0005 affected43 at risk EG0013 affected41 at risk EG0022 affected43 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0005 affected43 at risk EG0011 affected41 at risk EG0021 affected43 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected43 at risk EG0015 affected41 at risk EG00210 affected43 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected43 at risk EG0010 affected41 at risk EG0023 affected43 at risk EG003
Frequent bowel movements	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected43 at risk EG0011 affected41 at risk EG0024 affected43 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0005 affected43 at risk EG0018 affected41 at risk EG0027 affected43 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected43 at risk EG0010 affected41 at risk EG0021 affected43 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected43 at risk EG0010 affected41 at risk EG0024 affected43 at risk EG003
Influenza-like illness	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0010 affected41 at risk EG0023 affected43 at risk EG003
Injection site bruising	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected43 at risk EG0012 affected41 at risk EG0023 affected43 at risk EG003
Injection site erythema	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0014 affected41 at risk EG0026 affected43 at risk EG003
Injection site pruritus	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0012 affected41 at risk EG0023 affected43 at risk EG003
Influenza	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0003 affected43 at risk EG0012 affected41 at risk EG0021 affected43 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0004 affected43 at risk EG0010 affected41 at risk EG0020 affected43 at risk EG003
Sinusitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0015 affected41 at risk EG0021 affected43 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected43 at risk EG0010 affected41 at risk EG0020 affected43 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected43 at risk EG0011 affected41 at risk EG0022 affected43 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0012 affected41 at risk EG0022 affected43 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected43 at risk EG0013 affected41 at risk EG0022 affected43 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0011 affected41 at risk EG0022 affected43 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0004 affected43 at risk EG0010 affected41 at risk EG0021 affected43 at risk EG003
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0006 affected43 at risk EG0012 affected41 at risk EG0024 affected43 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected43 at risk EG0011 affected41 at risk EG0022 affected43 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected43 at risk EG0013 affected41 at risk EG0022 affected43 at risk EG003

First MCP Posted Date

ID	Term
D065626	Non-alcoholic Fatty Liver Disease

ID	Term
C000710649	aldafermin

Title	Measurements
	OG00014.43± 8.8 OG00110.62± 5.6 OG0027.03± 5.7 OG00316.00± 7.1

Title	Measurements
	OG00014.85± 9.3 OG00110.64± 6.2 OG0026.72± 5.6 OG00314.01± 6.2

Title	Measurements
	OG00016.30± 9.2 OG00115.36± 6.5 OG00213.10± 7.4 OG00314.27± 7.5

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