QUANTUM: Safety Study of Regimens of Sofosbuvir, GS-0938, and Ribavirin in Patients With Chronic Hepatitis C Infection

Sponsor

Gilead Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT01435044

Collaborator

Quintiles, Inc. (Industry)

239

Enrollment

Locations

Arms

Duration (Months)

5.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study was designed to assess the safety and efficacy of multiple interferon-free treatment regimens of sofosbuvir (Sovaldi™; GS-7977; PSI-7977) and GS-0938 (PSI-352938) alone and in combination, with and without ribavirin (RBV). Each regimen was to be evaluated over 12 and 24 weeks to identify the optimal duration of therapy to maximize the benefit (sustained virologic response [SVR]) versus risk (safety and resistance).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Sofosbuvir Drug: GS-0938 Drug: RBV Drug: Placebo to match sofosbuvir Drug: Placebo to match GS-0938	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

239 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

QUANTUM: An International, Multi-center, Blinded, Randomized Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Administration of Regimens Containing PSI-352938, PSI-7977, and Ribavirin in Patients With Chronic Hepatitis C Virus (HCV) Infection

Study Start Date :

Sep 1, 2011

Actual Primary Completion Date :

Apr 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOF+RBV 12 Weeks Participants were randomized to receive sofosbuvir plus RBV plus placebo to match GS-0938 for 12 weeks.	Drug: Sofosbuvir Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi™ GS-7977 PSI-7977 Drug: RBV Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) Other Names: Ribasphere®
Experimental: SOF+RBV 24 Weeks Participants were randomized to receive sofosbuvir plus RBV plus placebo to match GS-0938 for 24 weeks.	Drug: Sofosbuvir Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi™ GS-7977 PSI-7977 Drug: RBV Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) Other Names: Ribasphere®
Experimental: GS-0938 Alone Participants were randomized to receive GS-0938 plus placebo to match sofosbuvir for up to 24 weeks.	Drug: GS-0938 GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily Other Names: PSI-352938 Drug: Placebo to match sofosbuvir Placebo to match sofosbuvir administered orally once daily
Experimental: GS-0938+SOF Participants were randomized to receive GS-0938 plus sofosbuvir for up to 24 weeks.	Drug: Sofosbuvir Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi™ GS-7977 PSI-7977 Drug: GS-0938 GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily Other Names: PSI-352938
Experimental: GS-0938+SOF+RBV Participants were randomized to receive GS-0938 plus sofosbuvir plus RBV for up to 24 weeks.	Drug: Sofosbuvir Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi™ GS-7977 PSI-7977 Drug: GS-0938 GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily Other Names: PSI-352938 Drug: RBV Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) Other Names: Ribasphere®
Experimental: Placebo Deferred start group: Participants were randomized to receive placebo to match GS-0938 plus placebo to match sofosbuvir for 24 Weeks.	Drug: Placebo to match sofosbuvir Placebo to match sofosbuvir administered orally once daily Drug: Placebo to match GS-0938 Placebo to match GS-0938 administered orally once daily
Experimental: Retreatment Group - SOF+RBV 24 Weeks After discontinuing a regimen containing GS-0938, participants received sofosbuvir plus RBV for up to 24 weeks.	Drug: Sofosbuvir Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi™ GS-7977 PSI-7977 Drug: RBV Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) Other Names: Ribasphere®

Outcome Measures

Primary Outcome Measures

Percentage of participants with sustained virologic response (SVR) 12 weeks after discontinuation of study drug (SVR12) [Post-treatment Week 12]
SVR12 was defined as HCV RNA < LLOQ 12 weeks after the last dose of all study drugs.

Secondary Outcome Measures

Percentage of Participants Who Experienced Adverse Events [Baseline to Week 24 plus 30 days]
Adverse events (AEs) were summarized across the participant population. A participant was counted once if they had a qualifying event.
Change from baseline in HCV RNA [Baseline to Week 12]
Percentage of Participants With HCV RNA < LLOQ during treatment [Baseline to Week 12]
Percentage of Participants With ALT Normalization [Baseline to post-treatment Week 4]
ALT normalization was defined as ALT > ULN at baseline and ALT ≤ ULN at a subsequent visit.
Percentage of participants with SVR at 4 and 24 weeks after discontinuation of study drug (SVR4; SVR24) [Post-treatment Weeks 4 and 24]
SVR4 and SVR24 was defined as HCV RNA < LLOQ 4 and 24 weeks after the last dose of all study drugs, respectively.
Percentage of Participants Who Developed Resistance to Sofosbuvir [Baseline to Week 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Chronic HCV-infection
Naive to all HCV antiviral treatment
Otherwise healthy patients

Exclusion Criteria:

Positive test at Screening for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab
History of any other clinically significant chronic liver disease
Medical history which the investigator considers the patient unsuitable for the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Liver & Digestive Specialists	Montgomery	Alabama	United States	36116
2		Bakersfield	California	United States	93301
3		Coronado	California	United States	92118
4		La Mesa	California	United States	91942
5		Los Angeles	California	United States	90036
6	CLI	Los Angeles	California	United States	90048
7	UCSD Antiviral Research Center	San Diego	California	United States	92103
8	eStudy Site	San Diego	California	United States	92120
9	Medical Associates Research Group	San Diego	California	United States	92193
10	Quest Clinical Research	San Francisco	California	United States	94115
11		Denver	Colorado	United States	80220
12		Engelwood	Colorado	United States	80113
13	South Denver Gastroenterology	Englewood	Colorado	United States	80113
14		Washington	District of Columbia	United States	20009
15	Avail Clinical Research	Deland	Florida	United States	32720
16	University of Florida Hepatology	Gainesville	Florida	United States	32610
17	University of Miami Center for Liver Diseases	Miami	Florida	United States	33136
18	Orlando Immunology Center	Orlando	Florida	United States	32803
19	Internal Medicine Specialists	Orlando	Florida	United States	32806
20	Miami Research Associates	South Miami	Florida	United States	33143
21	Advanced Research Institute	Trinity	Florida	United States	34655
22	South Florida Center of Gastroenterology	Wellington	Florida	United States	33414
23	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30308
24		Atlanta	Georgia	United States	30308
25		Marietta	Georgia	United States	30060
26	Digestive Health Services	Downers Grove	Illinois	United States	60515
27	Investigative Clinical Research	Annapolis	Maryland	United States	21401
28		Baltimore	Maryland	United States	21229
29	ID Care	Hillsborough	New Jersey	United States	08844
30	Concorde Medical Group	New York	New York	United States	10016
31	Mount Sinai Medical Center	New York	New York	United States	10029
32	Ashville Gastroenterology Associates	Ashville	North Carolina	United States	28801
33	Carolina's Center for Liver Disease	Statesville	North Carolina	United States	28677
34	Digestive Health Specialists	Winston-Salem	North Carolina	United States	27103
35		Cincinnati	Ohio	United States
36	Gastro One	Germantown	Tennessee	United States	38138
37	Nashville Gastrointestinal Specialists	Nashville	Tennessee	United States	37211
38	Texas Clinical Research Institute	Arlington	Texas	United States	76012
39	Central Texas Clinical Research	Austin	Texas	United States	78705
40	Alamo Medical Research	San Antonio	Texas	United States	78215
41	Digestive and Liver Disease Specialists	Norfolk	Virginia	United States	23502
42	Virginia Mason Medical Center	Seattle	Washington	United States	98101
43		San Juan		Puerto Rico	00909
44	Fundacion de Investigacion de Diego	San Juan		Puerto Rico	00927