Comparison of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks With Sofosbuvir and Ribavirin for 12 Weeks in Adults With Chronic Genotype 2 HCV Infection (ASTRAL-2)

• ClinicalTrials.gov Identifier: NCT02220998
• Recruitment Status: Completed
• First Posted: August 20, 2014
• Results First Posted: November 15, 2016
• Last Update Posted: November 15, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: August 18, 2014
• First Posted Date: August 20, 2014
• Results First Submitted Date: July 27, 2016
• Results First Posted Date: November 15, 2016
• Last Update Posted Date: November 15, 2018
• Study Start Date: September 2014
• Actual Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2016)

• Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
  SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
• Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [ Time Frame: Up to 12 weeks ]

Original Primary Outcome Measures (submitted: August 18, 2014)

• Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
  SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
• Incidence of adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Up to 12 weeks ]

Current Secondary Outcome Measures (submitted: September 26, 2016)

• Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
  SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
• Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, and 12 ]
• Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 [ Time Frame: Baseline; Weeks 1, 2, 4, 6, 8, 10, and 12 ]
• Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ]
  Virologic failure was defined as

  • On-treatment virologic failure:
    • Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
    • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
    • Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
  • Virologic relapse:
    • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

Original Secondary Outcome Measures (submitted: August 18, 2014)

• Proportion of participants with sustained virologic response 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
  SVR4 and SVR24 are defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug.
• Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to 8 weeks ]
• HCV RNA change from baseline [ Time Frame: Up to 8 weeks ]
• Proportion of participants with virologic failure [ Time Frame: Up to Posttreatment Week 24 ]
  Virologic failure is defined as

  • On-treatment virologic failure
    • HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment,
    • > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment,
    • HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse)
  • Relapse
    • HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks With Sofosbuvir and Ribavirin for 12 Weeks in Adults With Chronic Genotype 2 HCV Infection
• Official Title: A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks With Sofosbuvir and Ribavirin for 12 Weeks in Subjects With Chronic Genotype 2 HCV Infection
• Brief Summary: The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of treatment with sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) for 12 weeks compared to treatment with sofosbuvir (SOF) plus ribavirin (RBV) for 12 weeks in participants with chronic genotype 2 hepatitis C virus (HCV) infection.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis C Virus Infection

Intervention

• Drug: SOF/VEL
  SOF/VEL (400/100 mg) FDC tablet administered orally once daily
  Other Names:

  • Epclusa®
  • GS-7977/GS-5816
• Drug: SOF
  SOF 400 mg tablet administered orally once daily
  Other Names:

  • Sovaldi®
  • GS-7977
  • PSI-7977
• Drug: RBV
  RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

Study Arms

• Experimental: SOF/VEL
  SOF/VEL FDC for 12 weeks
  Intervention: Drug: SOF/VEL
• Experimental: SOF+RBV
  SOF+RBV for 12 weeks
  Interventions:

  • Drug: SOF
  • Drug: RBV

Publications *

• Asselah T, Charlton M, Feld J, Foster GR, Mcnally J, Brainard DM, et al. The ASTRAL Studies: Evaluation of SOF/GS-5816 Single Tablet Regimen for the Treatment of Genotype 1-6 HCV Infection [Poster P1332]. J Hepatol 2015;62:S855-S6.
• Sulkowski, MS., Brau N., Lawitz E., Shiffman ML, Towner WL, Ruane PJ et al. A Randomized Controlled Trial of Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks Compared to Sofosbuvir with Ribavirin for 12 Weeks in Genotype 2 HCV Infected Patients: The Phase 3 ASTRAL-2 Study [Oral 205] Hepatology 2015; 62: 1 (SUPPL) 313A.
• Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourlière M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.
• Younossi ZM, Stepanova M, Feld J, Zeuzem S, Sulkowski M, Foster GR, Mangia A, Charlton M, O'Leary JG, Curry MP, Nader F, Henry L, Hunt S. Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis. Clin Gastroenterol Hepatol. 2017 Mar;15(3):421-430.e6. doi: 10.1016/j.cgh.2016.10.037. Epub 2016 Nov 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 5, 2015): 269
• Original Estimated Enrollment (submitted: August 18, 2014): 240
• Actual Study Completion Date: September 2015
• Actual Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Willing and able to provide written informed consent
• HCV RNA ≥ 10^4 IU/mL
• HCV genotype 2
• Chronic HCV infection (≥ 6 months)
• Females of childbearing potential must have a negative serum pregnancy test
• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Must be of generally good health, with the exception of chronic HCV infection, as determined by the investigator.

Exclusion Criteria:

• Current or prior history of clinically-significant illness (other than HCV that may interfere with treatment, assessment or compliance with the protocol;
• Screening electrocardiogram (ECG) with clinically significant abnormalities
• Laboratory results outside of acceptable ranges at Screening
• Pregnant or nursing female or male with pregnant female partner
• Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis)
• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT02220998
• Other Study ID Numbers: GS-US-342-1139
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: http://www.gilead.com/research/disclosure-and-transparency

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Anu Osinusi, MD; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: September 2016