Study of NGM282 in Patients With Nonalcoholic Steatohepatitis (NASH)

NCT02443116 — Phase 2, Completed, 254 participants, NGM Biopharmaceuticals, Inc

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A Phase 2, Randomized, Double-blind, Placebo-controlled Study With Additional Open-label, Single-blind and Placebo-controlled Cohorts to Assess the Safety, Tolerability, and Efficacy of NGM282 in Patients With Nonalcoholic Steatohepatitis

Registry	NCT02443116
Status	Completed
Phase	Phase 2
Study type	Interventional; randomized, parallel, masking: triple, treatment
Enrollment	254 (Actual)
Sponsor	NGM Biopharmaceuticals, Inc (Industry); collaborators: NGM Biopharmaceuticals Australia Pty Ltd
Conditions	Nonalcoholic Steatohepatitis (NASH)
Interventions	NGM282, Placebo (Biological, other)
Dates	start 2015-07-31, primary completion 2019-12-06, completion 2020-01-17, first posted 2015-05-13, last updated 2025-07-23
Locations	22 sites in United States, Australia, Puerto Rico

-Summary

The purpose of this study is to determine the safety, tolerability, and efficacy of NGM282 in patients with nonalcoholic steatohepatitis.

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+Arms and interventions

Arm	Type	Interventions	Description
Cohort 1 - Placebo	Placebo comparator	Other: Placebo	Cohort 1 - Placebo
Cohort 1 - NGM282 3mg	Experimental	Biological: NGM282	Cohort 1 - NGM282 3mg
Cohort 1 - NGM282 6mg	Experimental	Biological: NGM282	Cohort 1 - NGM282 6mg
Cohort 2 - NGM282 0.3mg	Experimental	Biological: NGM282	Cohort 2 - NGM282 0.3mg
Cohort 2 - NGM282 1mg	Placebo comparator	Biological: NGM282	Cohort 2 - NGM282 1mg
Cohort 2 - NGM282 3mg	Experimental	Biological: NGM282	Cohort 2 - NGM282 3mg
Cohort 3 - NGM282 1mg	Experimental	Biological: NGM282	Cohort 3 - NGM282 1mg
Cohort 4 - Placebo	Placebo comparator	Other: Placebo	Cohort 4 - Placebo
Cohort 4 - NGM282 1mg	Experimental	Biological: NGM282	Cohort 4 - NGM282 1mg

NGM282 (Biological)
Placebo (Other)

+Outcome measures

Primary outcomes

Change in Absolute Liver Fat Content (Part 1) [Up to Week 12]: Absolute liver fat content was assessed using magnetic resonance imaging (MRI).
Change in Absolute Liver Fat Content (Part 2) [Up to Week 12]: Absolute liver fat content was assessed using magnetic resonance imaging proton density fat fraction (MRI-PDFF).
Change in Absolute Liver Fat Content (Part 3) [Up to Week 24]: Absolute liver fat content was measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF).

Secondary outcomes

Percentage Change in Liver Fat Content (Part 1) [Up to Week 12]: Percentage change in liver fat content was assessed using magnetic resonance imaging (MRI).
Change in Absolute Liver Fat Content (Part 2) [Up to Week 18]: Absolute liver fat content was assessed using magnetic resonance imaging proton density fat fraction (MRI-PDFF).
Percentage Change in Liver Fat Content (Part 2) [Up to Week 18]: Percentage change in liver fat content was assessed using magnetic resonance imaging proton density fat fraction (MRI-PDFF).
Change in Absolute Liver Fat Content (Part 3) [Up to Week 30]: Absolute liver fat content was measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF).
Percentage Change in Liver Fat Content (Part 3) [Up to Week 30]: Percentage change in liver fat content was assessed using magnetic resonance imaging proton density fat fraction (MRI-PDFF).

+Eligibility

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Males or females, between 18 and 75 years of age, inclusive
* Histologically confirmed NASH diagnosis

Exclusion Criteria:

* Clinically significant acute or chronic liver disease
* Prior liver transplantation

+Posted results

Participant flow

Milestone	Part 1: Aldafermin 3.0 mg	Part 1: Aldafermin 6.0 mg	Part 1: Placebo
Started	27	28	27
Completed	25	24	23
Not completed	2	4	4

Outcome results

Change in Absolute Liver Fat Content (Part 1) (Primary), Least squares mean, percent of liver fat: Part 1: Aldafermin 3.0 mg -9.68 +/- 0.98; Part 1: Aldafermin 6.0 mg -11.91 +/- 1.00; Part 1: Placebo -0.85 +/- 0.99 (p <0.001)
Change in Absolute Liver Fat Content (Part 2) (Primary), Least squares mean, percent of liver fat: Part 2: Aldafermin 0.3 mg -4.95 +/- 1.07; Part 2: Aldafermin 1.0 mg -10.69 +/- 1.09; Part 2: Aldafermin 3.0 mg -11.55 +/- 1.08; Part 2: Aldafermin 1.0 mg (Cohort 4) -10.85 +/- 1.01 (p <0.0001)
Change in Absolute Liver Fat Content (Part 3) (Primary), Least squares mean, percent of liver fat: Part 3: Aldafermin 1.0 mg -7.70 +/- 0.82; Part 3: Placebo -2.73 +/- 1.29 (p 0.0018)
Percentage Change in Liver Fat Content (Part 1) (Secondary), Least squares mean, percentage change of liver fat content: Part 1: Aldafermin 3.0 mg -47.98 +/- 5.79; Part 1: Aldafermin 6.0 mg -60.09 +/- 5.92; Part 1: Placebo -2.57 +/- 5.85
Change in Absolute Liver Fat Content (Part 2) (Secondary), Least squares mean, percent of liver fat: Part 2: Aldafermin 0.3 mg -4.15 +/- 0.93; Part 2: Aldafermin 1.0 mg -8.21 +/- 0.97; Part 2: Aldafermin 3.0 mg -10.38 +/- 0.94; Part 2: Aldafermin 1.0 mg (Cohort 4) -8.36 +/- 0.87
Percentage Change in Liver Fat Content (Part 2) (Secondary), Least squares mean, percentage change of liver fat content: Part 2: Aldafermin 0.3 mg -24.95 +/- 4.94; Part 2: Aldafermin 1.0 mg -42.90 +/- 5.19; Part 2: Aldafermin 3.0 mg -58.72 +/- 5.01; Part 2: Aldafermin 1.0 mg (Cohort 4) -45.92 +/- 4.63
Change in Absolute Liver Fat Content (Part 3) (Secondary), Least squares mean, percent of liver fat: Part 3: Aldafermin 1.0 mg -6.54 +/- 0.59; Part 3: Placebo -0.93 +/- 0.89
Percentage Change in Liver Fat Content (Part 3) (Secondary), Least squares mean, percentage change of liver fat content: Part 3: Aldafermin 1.0 mg -36.59 +/- 3.22; Part 3: Placebo -2.17 +/- 4.81

Adverse events

Time frame: Treatment-emergent adverse events were collected from Screening (Day -28 to Day -1) up to Week 30.

Arm	Deaths	Serious adverse events	Other adverse events
Part 1: Aldafermin 3.0 mg	0/27 (0.0%)	1/27 (3.7%)	26/27 (96.3%)
Part 1: Aldafermin 6.0 mg	0/28 (0.0%)	0/28 (0.0%)	27/28 (96.4%)
Part 1: Placebo	0/27 (0.0%)	0/27 (0.0%)	23/27 (85.2%)
Part 2: Aldafermin 0.3 mg	0/23 (0.0%)	0/23 (0.0%)	20/23 (87.0%)
Part 2: Aldafermin 1.0 mg	0/21 (0.0%)	1/21 (4.8%)	19/21 (90.5%)
Part 2: Aldafermin 3.0 mg	0/22 (0.0%)	4/22 (18.2%)	21/22 (95.5%)
Part 2: Aldafermin 1.0 mg (Cohort 4)	0/28 (0.0%)	1/28 (3.6%)	27/28 (96.4%)
Part 3: Aldafermin 1.0 mg	0/53 (0.0%)	2/53 (3.8%)	46/53 (86.8%)
Part 3: Placebo	0/25 (0.0%)	3/25 (12.0%)	22/25 (88.0%)

Serious adverse events by term

Term	Organ system	Part 1: Aldafermin 3.0 mg	Part 1: Aldafermin 6.0 mg	Part 1: Placebo	Part 2: Aldafermin 0.3 mg	Part 2: Aldafermin 1.0 mg	Part 2: Aldafermin 3.0 mg	Part 2: Aldafermin 1.0 mg (Cohort 4)	Part 3: Aldafermin 1.0 mg	Part 3: Placebo
Acute pancreatitis	Gastrointestinal disorders	1/27	0/28	0/27	0/23	0/21	0/22	0/28	0/53	0/25
Cardiac arrest	Cardiac disorders	0/27	0/28	0/27	0/23	0/21	1/22	0/28	0/53	0/25
Vertigo positional	Ear and labyrinth disorders	0/27	0/28	0/27	0/23	1/21	0/22	0/28	0/53	0/25
Chest pain	General disorders	0/27	0/28	0/27	0/23	0/21	1/22	0/28	0/53	0/25
Pneumonia	Infections and infestations	0/27	0/28	0/27	0/23	0/21	1/22	0/28	0/53	0/25
Headache	Nervous system disorders	0/27	0/28	0/27	0/23	1/21	0/22	0/28	0/53	0/25
Renal mass	Renal and urinary disorders	0/27	0/28	0/27	0/23	0/21	0/22	1/28	0/53	0/25
Pleurisy	Respiratory, thoracic and mediastinal disorders	0/27	0/28	0/27	0/23	0/21	1/22	0/28	0/53	0/25
Accelerated hypertension	Vascular disorders	0/27	0/28	0/27	0/23	1/21	0/22	0/28	0/53	0/25
Anxiety	Psychiatric disorders	0/27	0/28	0/27	0/23	0/21	0/22	0/28	0/53	1/25
Mental status changes	Psychiatric disorders	0/27	0/28	0/27	0/23	0/21	0/22	0/28	0/53	1/25
Suicidal ideation	Psychiatric disorders	0/27	0/28	0/27	0/23	0/21	0/22	0/28	0/53	1/25
Rectal haemorrhage	Gastrointestinal disorders	0/27	0/28	0/27	0/23	0/21	0/22	0/28	1/53	0/25
Appendicitis	Infections and infestations	0/27	0/28	0/27	0/23	0/21	0/22	0/28	0/53	1/25
Post procedural complication	Injury, poisoning and procedural complications	0/27	0/28	0/27	0/23	0/21	0/22	0/28	1/53	0/25

Other adverse events by term

Term	Organ system	Part 1: Aldafermin 3.0 mg	Part 1: Aldafermin 6.0 mg	Part 1: Placebo	Part 2: Aldafermin 0.3 mg	Part 2: Aldafermin 1.0 mg	Part 2: Aldafermin 3.0 mg	Part 2: Aldafermin 1.0 mg (Cohort 4)	Part 3: Aldafermin 1.0 mg	Part 3: Placebo
Loose stools	Gastrointestinal disorders	7/27	5/28	2/27	1/23	3/21	5/22	6/28	0/53	0/25
Nausea	Gastrointestinal disorders	8/27	3/28	1/27	2/23	6/21	6/22	12/28	5/53	6/25
Diarrhea	Gastrointestinal disorders	2/27	3/28	4/27	0/23	3/21	2/22	8/28	15/53	6/25
Vomiting	Gastrointestinal disorders	2/27	5/28	0/27	2/23	3/21	2/22	6/28	3/53	1/25
Abdominal pain	Gastrointestinal disorders	3/27	3/28	0/27	1/23	1/21	1/22	2/28	2/53	1/25
Bloating	Gastrointestinal disorders	1/27	4/28	0/27	0/23	2/21	0/22	1/28	0/53	0/25
Constipation	Gastrointestinal disorders	3/27	1/28	1/27	1/23	1/21	1/22	5/28	3/53	1/25
Nausea aggravated	Gastrointestinal disorders	2/27	2/28	0/27	0/23	0/21	1/22	1/28	0/53	0/25
Abdominal bloating	Gastrointestinal disorders	2/27	0/28	1/27	0/23	0/21	0/22	1/28	0/53	0/25
Diarrhea aggravated	Gastrointestinal disorders	2/27	0/28	0/27	1/23	0/21	0/22	0/28	0/53	0/25
Hemorrhoids	Gastrointestinal disorders	0/27	2/28	0/27	0/23	0/21	0/22	0/28	0/53	0/25
RUQ pain	Gastrointestinal disorders	2/27	0/28	1/27	0/23	1/21	0/22	0/28	0/53	0/25
Soft stools	Gastrointestinal disorders	1/27	2/28	0/27	1/23	1/21	0/22	0/28	0/53	0/25
GERD	Gastrointestinal disorders	2/27	0/28	0/27	1/23	1/21	0/22	0/28	4/53	0/25
Increased frequency of defecation	Gastrointestinal disorders	2/27	0/28	0/27	1/23	2/21	1/22	0/28	0/53	0/25
Stomach cramps	Gastrointestinal disorders	0/27	2/28	0/27	0/23	0/21	0/22	1/28	0/53	0/25
Injection site erythema	General disorders	6/27	11/28	2/27	0/23	2/21	0/22	1/28	0/53	0/25
Injection site reaction	General disorders	3/27	4/28	0/27	1/23	0/21	1/22	1/28	2/53	0/25
Injection site bruising	General disorders	2/27	0/28	3/27	1/23	0/21	0/22	0/28	3/53	0/25
Injection site pruritus	General disorders	2/27	3/28	0/27	0/23	1/21	0/22	3/28	1/53	0/25
Fatigue	General disorders	0/27	2/28	2/27	3/23	3/21	1/22	6/28	3/53	4/25
Injection site pain	General disorders	0/27	2/28	1/27	0/23	0/21	0/22	0/28	0/53	1/25
Injection site swelling	General disorders	3/27	0/28	0/27	0/23	0/21	0/22	0/28	0/53	0/25
Headache	Nervous system disorders	3/27	5/28	5/27	5/23	4/21	4/22	4/28	7/53	9/25
Dysgeusia	Nervous system disorders	1/27	1/28	2/27	0/23	1/21	0/22	0/28	1/53	2/25
Dizziness	Nervous system disorders	2/27	1/28	0/27	0/23	1/21	0/22	4/28	1/53	0/25
Upper respiratory tract infection	Infections and infestations	1/27	2/28	2/27	2/23	1/21	0/22	1/28	1/53	1/25
Sinusitis	Infections and infestations	2/27	1/28	1/27	1/23	1/21	0/22	2/28	4/53	2/25
Urinary tract infection	Infections and infestations	2/27	2/28	0/27	0/23	1/21	4/22	3/28	2/53	2/25
Nasopharyngitis	Infections and infestations	0/27	0/28	2/27	0/23	1/21	0/22	5/28	2/53	1/25
Increased appetite	Metabolism and nutrition disorders	2/27	4/28	0/27	0/23	2/21	1/22	1/28	1/53	0/25
Weight decreased	Investigations	0/27	3/28	0/27	0/23	0/21	0/22	0/28	0/53	0/25
Blood creatinine increased	Investigations	2/27	0/28	0/27	0/23	0/21	1/22	0/28	1/53	1/25
Weight increased	Investigations	2/27	0/28	0/27	0/23	0/21	0/22	1/28	1/53	0/25
Pruritus	Skin and subcutaneous tissue disorders	2/27	0/28	1/27	0/23	0/21	0/22	2/28	2/53	2/25
Arthralgia	Musculoskeletal and connective tissue disorders	1/27	1/28	2/27	1/23	0/21	1/22	0/28	4/53	0/25
Back pain	Musculoskeletal and connective tissue disorders	0/27	2/28	0/27	0/23	2/21	1/22	1/28	2/53	1/25
Hypertension	Vascular disorders	1/27	2/28	0/27	0/23	0/21	0/22	0/28	2/53	2/25
Haematuria	Renal and urinary disorders	0/27	2/28	0/27	0/23	0/21	0/22	0/28	0/53	0/25
Abdominal cramp	Gastrointestinal disorders	1/27	1/28	0/27	1/23	0/21	0/22	2/28	0/53	0/25
Emesis	Gastrointestinal disorders	0/27	0/28	0/27	0/23	0/21	2/22	0/28	0/53	0/25
Frequent bowel movements	Gastrointestinal disorders	0/27	0/28	0/27	0/23	0/21	2/22	0/28	3/53	0/25
Stool discoloration	Gastrointestinal disorders	1/27	1/28	0/27	0/23	2/21	0/22	0/28	0/53	0/25
Low density lipoprotein increased	Investigations	1/27	0/28	0/27	9/23	15/21	9/22	13/28	0/53	0/25
Blood cholesterol increased	Investigations	0/27	0/28	0/27	0/23	2/21	4/22	7/28	0/53	0/25
Glycosylated hemoglobin increased	Investigations	0/27	0/28	0/27	0/23	0/21	0/22	2/28	0/53	0/25
Bronchitis	Infections and infestations	0/27	0/28	0/27	1/23	2/21	1/22	1/28	2/53	0/25
Influenza	Infections and infestations	1/27	1/28	0/27	0/23	0/21	0/22	2/28	0/53	0/25
Vitamin D deficiency	Metabolism and nutrition disorders	0/27	0/28	0/27	2/23	4/21	4/22	6/28	1/53	0/25
Chest pain	General disorders	0/27	0/28	1/27	0/23	0/21	2/22	0/28	0/53	0/25
Muscle spasms	Musculoskeletal and connective tissue disorders	1/27	0/28	0/27	0/23	0/21	0/22	2/28	1/53	0/25
Pain in extremity	Musculoskeletal and connective tissue disorders	1/27	0/28	0/27	0/23	2/21	0/22	0/28	4/53	1/25
Cough	Respiratory, thoracic and mediastinal disorders	1/27	1/28	1/27	0/23	2/21	4/22	2/28	0/53	1/25
Dyspnoea	Respiratory, thoracic and mediastinal disorders	0/27	0/28	0/27	0/23	0/21	0/22	2/28	0/53	0/25
Contusion	Injury, poisoning and procedural complications	0/27	0/28	0/27	2/23	0/21	1/22	0/28	0/53	0/25
Procedural pain	Injury, poisoning and procedural complications	1/27	0/28	0/27	0/23	0/21	0/22	2/28	4/53	0/25
Pollakiuria	Renal and urinary disorders	0/27	1/28	0/27	0/23	1/21	0/22	2/28	0/53	0/25
Nephrolithiasis	Renal and urinary disorders	0/27	0/28	0/27	2/23	0/21	0/22	0/28	2/53	0/25
Insomnia	Psychiatric disorders	0/27	0/28	1/27	1/23	2/21	0/22	0/28	3/53	0/25
Seasonal allergy	Immune system disorders	0/27	0/28	1/27	0/23	1/21	0/22	2/28	0/53	0/25

6 more terms not shown.

+Locations (22)

Facility	City	Country
NGM Clinical Study Site 922	Chandler, Arizona	United States
NGM Clinical Study Site 923	Tucson, Arizona	United States
NGM Clinical Study Site 924	Los Angeles, California	United States
NGM Clinical Study Site 901	San Diego, California	United States
NGM Clinical Study Site 902	Denver, Colorado	United States
NGM Clinical Study Site 917	Lakewood Rch, Florida	United States
NGM Clinical Study Site 906	Chicago, Illinois	United States
NGM Clinical Study Site 918	Kansas City, Missouri	United States
NGM Clinical Study Site 903	Durham, North Carolina	United States
NGM Clinical Study Site 921	Germantown, Tennessee	United States
NGM Clinical Study Site 910	Dallas, Texas	United States
NGM Clinical Study Site 920	Rollingwood, Texas	United States
NGM Clinical Study Site 909	San Antonio, Texas	United States
NGM Clinical Study Site 905	San Antonio, Texas	United States
NGM Clinical Study Site 904	Charlottesville, Virginia	United States
NGM Clinical Study Site 911	Richmond, Virginia	United States
NGM Clinical Study Site 908	Seattle, Washington	United States
NGM Clinical Study Site 703	Sydney, New South Wales	Australia
NGM Clinical Study Site 704	Adelaide, South Australia	Australia
NGM Clinical Study Site 701	Melbourne, Victoria	Australia
NGM Clinical Study Site 705	Melbourne, Victoria	Australia
NGM Clinical Study Site 916	San Juan	Puerto Rico

+Publications

Results publication: Alkhouri N, Beyer C, Shumbayawonda E, Andersson A, Yale K, Rolph T, Chung RT, Vuppalanchi R, Cusi K, Loomba R, Pansini M, Dennis A. Decreases in cT1 and liver fat content reflect treatment-induced histological improvements in MASH. J Hepatol. 2025 Mar;82(3):438-445. doi: 10.1016/j.jhep.2024.08.031. Epub 2024 Sep 25. PMID 39326675
Results publication: Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1. PMID 36318027
Results publication: Sanyal AJ, Ling L, Beuers U, DePaoli AM, Lieu HD, Harrison SA, Hirschfield GM. Potent suppression of hydrophobic bile acids by aldafermin, an FGF19 analogue, across metabolic and cholestatic liver diseases. JHEP Rep. 2021 Feb 19;3(3):100255. doi: 10.1016/j.jhepr.2021.100255. eCollection 2021 Jun. PMID 33898959
Results publication: Loomba R, Ling L, Dinh DM, DePaoli AM, Lieu HD, Harrison SA, Sanyal AJ. The Commensal Microbe Veillonella as a Marker for Response to an FGF19 Analog in NASH. Hepatology. 2021 Jan;73(1):126-143. doi: 10.1002/hep.31523. Epub 2020 Dec 11. PMID 32794259
Results publication: Harrison SA, Neff G, Guy CD, Bashir MR, Paredes AH, Frias JP, Younes Z, Trotter JF, Gunn NT, Moussa SE, Kohli A, Nelson K, Gottwald M, Chang WCG, Yan AZ, DePaoli AM, Ling L, Lieu HD. Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis. Gastroenterology. 2021 Jan;160(1):219-231.e1. doi: 10.1053/j.gastro.2020.08.004. Epub 2020 Aug 8. PMID 32781086
Results publication: Harrison SA, Rinella ME, Abdelmalek MF, Trotter JF, Paredes AH, Arnold HL, Kugelmas M, Bashir MR, Jaros MJ, Ling L, Rossi SJ, DePaoli AM, Loomba R. NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2018 Mar 24;391(10126):1174-1185. doi: 10.1016/S0140-6736(18)30474-4. Epub 2018 Mar 5. PMID 29519502

+Study documents

Study Protocol (PDF, 2019-03-29)
Statistical Analysis Plan (PDF, 2019-10-01)

+Investigators

NGM Study Director, Study director, NGM Biopharmaceuticals, Inc

My Notes

Public

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