Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 HCV and HIV-1 Co-infection

Browse trials for

• Hepatitis C 2,321
• Coinfection 154
• Hepatitis 3,380

Keywords

• genotype 1
• genotype 4
• HIV

Hepatitis C

2,321 studies on the registry are indexed under Hepatitis C; 102 are open to participants now.

This study's enrollment of 335 is above the median of 79 across 1,633 interventional studies indexed under Hepatitis C.

Lead sponsor

Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.

Study arms

• Experimental
  LDV/SOF 12 Weeks

  LDV/SOF for 12 weeks

  Drug: LDV/SOF

• Experimental
  Retreatment Substudy

  LDV/SOF plus RBV for 24 weeks

  Drug: LDV/SOF · Drug: RBV

Interventions

• DrugLDV/SOF

  90/400 mg FDC tablet administered orally once daily

  Also known as: Harvoni®, GS-5885/GS-7977

• DrugRBV

  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)

Primary outcomes

1. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

   SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.

   Time frame: Posttreatment Week 12

2. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event

   Time frame: Up to 12 weeks

Secondary outcomes

1. Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

   SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.

   Time frame: Posttreatment Weeks 4 and 24

2. 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

3. Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8

   Time frame: Baseline; Weeks 1, 2, 4, 6, and 8

4. Percentage of Participants With Virologic Failure

   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.

   Time frame: Up to Posttreatment Week 24

5. Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment

   Time frame: Weeks 4, 8, and 12

6. Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24

   Time frame: Baseline; Week 12, Posttreatment Weeks 12 and 24

7. For Participants in the Retreatment Substudy, Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)

   SVR4, SVR12, and SVR 24 were defined as HCV RNA \< LLOQ at 4, 12, and 24 weeks after stopping study treatment, respectively.

   Time frame: Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy

8. For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24

   Time frame: Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy

9. For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8

   Time frame: Baseline; Weeks 2, 4, and 8 of Retreatment Substudy

10. For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure

    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.

    Time frame: Up to Posttreatment Week 24 of Retreatment Substudy

Baseline characteristics

6 further baseline measures are reported on the registry.

Publications

• Cooper C, Naggie S, Saag M, Yang JC, Stamm LM, Dvory-Sobol H, et al. Retreatment of Patients Who Failed 12 Weeks of Ledipasvir/Sofosbuvir-Based Regimens with Ledipasvir/Sofosbuvir with Ribavirin for 24 Weeks [Poster Presentation]. 23nd Conference on Retroviruses and Opportunistic Infections (CROI); 2016 February 22-25; Boston, MA.
• Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, Marks K, Luetkemeyer A, Baden RP, Sax PE, Gane E, Santana-Bagur J, Stamm LM, Yang JC, German P, Dvory-Sobol H, Ni L, Pang PS, McHutchison JG, Stedman CA, Morales-Ramirez JO, Brau N, Jayaweera D, Colson AE, Tebas P, Wong DK, Dieterich D, Sulkowski M; ION-4 Investigators. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):705-13. doi: 10.1056/NEJMoa1501315. Epub 2015 Jul 21. PubMed 26196665 ↗
• Naggie S, Cooper C, Saag M, Stamm LM, Yang JC, Pang PS, et al. Ledipasvir/Sofosbuvir for 12 Weeks in Patients Coinfected With HCV and HIV-1 [Oral Presentation]. 22nd Conference on Retroviruses and Opportunistic Infections (CROI); 2015 February 23-26; Seattle, WA.
• Cooper C, Naggie S, Saag M, Yang JC, Stamm LM, Dvory-Sobol H, Han L, Pang PS, McHutchison JG, Dieterich D, Sulkowski M. Successful Re-treatment of Hepatitis C Virus in Patients Coinfected With HIV Who Relapsed After 12 Weeks of Ledipasvir/Sofosbuvir. Clin Infect Dis. 2016 Aug 15;63(4):528-31. doi: 10.1093/cid/ciw349. Epub 2016 May 25. PubMed 27225242 ↗
• Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferriere V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study; Cohen J, Conway B, Cooper C, Cote P, Cox J, Gill J, Haider S, Harris M, Haase D, Hull M, Montaner J, Moodie E, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall JM, Vachon ML, Walmsley S, Wong D. How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World? Clin Infect Dis. 2016 Apr 1;62(7):919-926. doi: 10.1093/cid/civ1222. Epub 2016 Jan 6. PubMed 26743093 ↗

Individual participant data

Plan to share: Yes — 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 information: Study protocol, Sap