Study to Evaluate Safety, Tolerability, and Efficacy of GS-0976 in Adults With Nonalcoholic Steatohepatitis

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02856555
• Collaborator: (none)
• Enrollment: 127
• Locations: 36
• Arms: 3
• Actual Duration (Months): 11.3
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of firsocostat in adults with nonalcoholic steatohepatitis (NASH).

Condition or Disease	Intervention/Treatment	Phase
Nonalcoholic Steatohepatitis (NASH)	Drug: Firsocostat; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-0976 in Subjects With Nonalcoholic Steatohepatitis
• Actual Study Start Date: Aug 8, 2016
• Actual Primary Completion Date: Jul 18, 2017
• Actual Study Completion Date: Jul 18, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Firsocostat 5 mg Participants will receive firsocostat 1 x 5 mg + 1 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg for 12 weeks.	Drug: Firsocostat; Capsules orally once daily.; Other Names: GS-0976 ; Drug: Placebo; Placebo matched to firsocostat orally once daily.
Experimental: Firsocostat 20 mg Participants will receive firsocostat 2 X 10 mg + 2 x placebo matched to firsocostat 5 mg for 12 weeks.	Drug: Firsocostat; Capsules orally once daily.; Other Names: GS-0976 ; Drug: Placebo; Placebo matched to firsocostat orally once daily.
Experimental: Placebo Participants will receive 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg for 12 weeks.	Drug: Placebo; Placebo matched to firsocostat orally once daily.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [First Dose date up to last dose (Week 12) plus 30 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Meets all of the following conditions:

• A clinical diagnosis of nonalcoholic fatty liver disease (NAFLD)

• Screening magnetic resonance imaging - proton density fat fraction (MRI-PDFF) with ≥ 8% steatosis

• Screening magnetic resonance elastography (MRE) with liver stiffness ≥ 2.5 kPa

• OR

• A historical liver biopsy consistent with NASH and non-cirrhotic fibrosis

• Platelet count ≥ 100,000/mm^3

• Creatinine Clearance (CLcr ) as calculated by the Cockcroft-Gault equation ≥ 60 ml/min

Key Exclusion Criteria:

• Pregnant or lactating females

• Alanine aminotransferase (ALT) > 5 x upper limit of the normal range (ULN)

• Other causes of liver disease including autoimmune, viral, and alcoholic liver disease

• Cirrhosis of the liver

• Prior history of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding

• Body mass index (BMI) < 18 kg/m^2

• International normalized ratio (INR) > 1.2 unless on anticoagulant therapy

• Total bilirubin > 1 x ULN, except with diagnosis of Gilbert's syndrome

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Coronado	California	United States	92118
2		Foster City	California	United States	94404
3		Los Angeles	California	United States	90036
4		Los Angeles	California	United States	90048
5		Rialto	California	United States	92377
6		San Diego	California	United States	92103
7		San Diego	California	United States	92123
8		San Francisco	California	United States	94115
9		San Francisco	California	United States	94143
10		Miami	Florida	United States	33136
11		Miami	Florida	United States	33165
12		Atlanta	Georgia	United States	30308
13		Chicago	Illinois	United States	60611
14		Indianapolis	Indiana	United States	46202
15		New Orleans	Louisiana	United States	70112
16		Boston	Massachusetts	United States	02115
17		Rochester	Minnesota	United States	55905
18		Kansas City	Missouri	United States	64131
19		New York	New York	United States	10016
20		Durham	North Carolina	United States	27710
21		Statesville	North Carolina	United States	28677
22		Philadelphia	Pennsylvania	United States	19707
23		Pittsburgh	Pennsylvania	United States	15213
24		Germantown	Tennessee	United States	38138
25		Memphis	Tennessee	United States	38104
26		Nashville	Tennessee	United States	37211
27		Arlington	Texas	United States	76012
28		Live Oak	Texas	United States	78233
29		San Antonio	Texas	United States	78215
30		Murray	Utah	United States	84107
31		Falls Church	Virginia	United States	22042
32		Richmond	Virginia	United States	23226
33		Richmond	Virginia	United States	23249
34		Richmond	Virginia	United States	23298
35		Richland	Washington	United States	99352
36		Seattle	Washington	United States	98104

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Dec 15, 2016
• Statistical Analysis Plan - Jul 21, 2017

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02856555
• Other Study ID Numbers: GS-US-426-3989
• First Posted: Aug 5, 2016
• Last Update Posted: Jul 24, 2020
• Last Verified: Jul 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Firsocostat

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in United States. The first participant was screened on 08 August 2016. The last study visit occurred on 18 July 2017.
Pre-assignment Detail	433 participants were screened.

Arm/Group Title	Firsocostat 5 mg	Firsocostat 20 mg	Placebo
Arm/Group Description	Participants received firsocostat 1 x 5 mg + 1 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks.	Participants received firsocostat 2 x 10 mg + 2 x placebo matched to firsocostat 5 mg capsules orally once daily for 12 weeks.	Participants received 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks.
Period Title: Overall Study
STARTED	51	50	26
COMPLETED	46	46	26
NOT COMPLETED	5	4	0

Baseline Characteristics

Arm/Group Title	Firsocostat 5 mg	Firsocostat 20 mg	Placebo	Total
Arm/Group Description	Participants received firsocostat 1 x 5 mg + 1 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks.	Participants received firsocostat 2 x 10 mg + 2 x placebo matched to firsocostat 5 mg capsules orally once daily for 12 weeks.	Participants received 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks.	Total of all reporting groups
Overall Participants	51	49	26	126
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (11.6)	54 (12.2)	56 (9.6)	54 (11.5)
Sex: Female, Male (Count of Participants)
Female	30 58.8%	33 67.3%	19 73.1%	82 65.1%
Male	21 41.2%	16 32.7%	7 26.9%	44 34.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 31.4%	23 46.9%	8 30.8%	47 37.3%
Not Hispanic or Latino	35 68.6%	26 53.1%	18 69.2%	79 62.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 2%	0 0%	1 3.8%	2 1.6%
Asian	5 9.8%	1 2%	1 3.8%	7 5.6%
Black or African American	3 5.9%	2 4.1%	1 3.8%	6 4.8%
White	42 82.4%	44 89.8%	23 88.5%	109 86.5%
Others	0 0%	2 4.1%	0 0%	2 1.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame	First Dose date up to last dose (Week 12) plus 30 days

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included participants who received at least 1 dose of study drug.

Arm/Group Title	Firsocostat 5 mg	Firsocostat 20 mg	Placebo
Arm/Group Description	Participants received firsocostat 1 x 5 mg + 1 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks.	Participants received firsocostat 2 x 10 mg + 2 x placebo matched to firsocostat 5 mg capsules orally once daily for 12 weeks.	Participants received 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks.
Measure Participants	51	49	26
Number [percentage of participants]	70.6 138.4%	71.4 145.7%	61.5 236.5%

Adverse Events

Time Frame	First Dose date up to last dose (Week 12) plus 30 days
Adverse Event Reporting Description	The Safety Analysis Set included participants who received at least 1 dose of study drug.
Arm/Group Title	Firsocostat 5 mg		Firsocostat 20 mg		Placebo
Arm/Group Description	Participants received firsocostat 1 x 5 mg + 1 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks.		Participants received firsocostat 2 x 10 mg + 2 x placebo matched to firsocostat 5 mg capsules orally once daily for 12 weeks.		Participants received 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks.
All Cause Mortality
	Firsocostat 5 mg		Firsocostat 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/49 (0%)		0/26 (0%)
Serious Adverse Events
	Firsocostat 5 mg		Firsocostat 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/51 (3.9%)		2/49 (4.1%)		0/26 (0%)
Gastrointestinal disorders
Abdominal pain	0/51 (0%)		1/49 (2%)		0/26 (0%)
General disorders
Pyrexia	1/51 (2%)		0/49 (0%)		0/26 (0%)
Infections and infestations
Diverticulitis	1/51 (2%)		0/49 (0%)		0/26 (0%)
Sepsis	0/51 (0%)		1/49 (2%)		0/26 (0%)
Nervous system disorders
Hepatic encephalopathy	0/51 (0%)		1/49 (2%)		0/26 (0%)
Transient ischaemic attack	0/51 (0%)		1/49 (2%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Firsocostat 5 mg		Firsocostat 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/51 (51%)		29/49 (59.2%)		11/26 (42.3%)
Gastrointestinal disorders
Nausea	4/51 (7.8%)		7/49 (14.3%)		2/26 (7.7%)
Diarrhoea	5/51 (9.8%)		6/49 (12.2%)		0/26 (0%)
Abdominal pain	2/51 (3.9%)		5/49 (10.2%)		1/26 (3.8%)
Abdominal pain upper	2/51 (3.9%)		4/49 (8.2%)		1/26 (3.8%)
Vomiting	1/51 (2%)		5/49 (10.2%)		0/26 (0%)
Constipation	2/51 (3.9%)		0/49 (0%)		2/26 (7.7%)
General disorders
Fatigue	2/51 (3.9%)		4/49 (8.2%)		3/26 (11.5%)
Chest discomfort	0/51 (0%)		0/49 (0%)		2/26 (7.7%)
Infections and infestations
Sinusitis	2/51 (3.9%)		3/49 (6.1%)		3/26 (11.5%)
Influenza	0/51 (0%)		5/49 (10.2%)		1/26 (3.8%)
Viral upper respiratory tract infection	3/51 (5.9%)		1/49 (2%)		0/26 (0%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	5/51 (9.8%)		1/49 (2%)		0/26 (0%)
Nervous system disorders
Headache	5/51 (9.8%)		4/49 (8.2%)		1/26 (3.8%)
Psychiatric disorders
Anxiety	3/51 (5.9%)		0/49 (0%)		1/26 (3.8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/51 (5.9%)		1/49 (2%)		0/26 (0%)
Dyspnoea	1/51 (2%)		0/49 (0%)		2/26 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years