A Phase 3 Study to Evaluate Combination Therapy With Daclatasvir and Sofosbuvir in the Treatment of HIV and Hepatitis C Virus Coinfection.

• ClinicalTrials.gov Identifier: NCT02032888
• Recruitment Status: Completed
• First Posted: January 10, 2014
• Results First Posted: October 27, 2015
• Last Update Posted: October 27, 2015
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: January 9, 2014
• First Posted Date: January 10, 2014
• Results First Submitted Date: August 21, 2015
• Results First Posted Date: October 27, 2015
• Last Update Posted Date: October 27, 2015
• Study Start Date: February 2014
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 24, 2015)

Percentage of Genotype 1 Hepatitis C Virus (HCV)-Infected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) [ Time Frame: At follow-up Week 12 ]

SVR12 was defined as HCV RNA <lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.

Original Primary Outcome Measures (submitted: January 9, 2014)

Proportion of treatment-naive subjects with sustained virologic response 12 (SVR12) [ Time Frame: Post treatment Week 12 ]

SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12 for the treatment-naive HCV genotype 1 subjects coinfected with HIV on the DCV+SOF 12-week regimen

Current Secondary Outcome Measures (submitted: September 24, 2015)

• Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) [ Time Frame: At follow-up Week 12 ]
  SVR12 was defined as HCV RNA<lower limit of quantitation, target detected, or target not detected, at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
• Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-experienced Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) [ Time Frame: At follow-up Week 12 ]
  SVR12 was defined as HCV RNA <lower limit of quantitation, target detected or target not detected, at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
• Percentage of Participants of All Genotypes Coinfected With Hepatitis C Virus (HCV)/HIV Who Achieved Sustained Virologic Response Rate at Follow-up Week 12 (SVR12) [ Time Frame: At follow-up Week 12 ]
  SVR12 was defined as HCV RNA levels <lower limit of quantitation, target detected or target not detected. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
• Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels to be <Lower Limit of Quantitation, Target Detected (TD)or Target Not Detected (TND) at Weeks: 1, 2, 4, 6, 8, and 12; at End of Treatment; and at Follow-up Weeks 4 and 24 [ Time Frame: Week 1, 2, 4, 6, 8, 12, End of treatment, and follow-up Week 4 and 24 ]
  Participants with hepatitis C virus CV) levels to be <lower limit of quantitation, TD or TND at each visit. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
• Percentage of Participants Coinfected With Hepatitis C Virus/HIV Who Achieved HCV RNA Levels<Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) [ Time Frame: At Weeks 1, 2, 4, 6, 8, and 12 and at End of Treatment ]
  Participants with HCV RNA levels <LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
• Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms Who Achieved Sustained Virologic Response at Follow-up Week 12 (SVR12) [ Time Frame: At Follow-up Week 12 ]
  SVR is defined as hepatitis C virus RNA <lower limit of quantitation, target detected or target not detected at follow-up Week 12. Percentage calculated as number of responders/number of patients receiving treatment.
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Interruption or Discontinuation, Treatment-related AEs/SAEs and Grade 3 to 4 AEs/SAEs and Who Died During Treatment Period [ Time Frame: AEs: Day 1 to 7 days after last dose of study treatment (8 weeks or 12 weeks). SAEs: Day 1 to 30 days after last dose of study treatment (8 weeks or 12 weeks) ]
  AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Who Died During Follow-up Period [ Time Frame: AEs: Day 1 of follow-up period (Week 9 or Week 13) to 7 days after end of 24 weeks follow-up period. SAEs: Day 1 of follow-up period (Week 9 or Week 13) to 30 days after end of 24 weeks follow-up period. ]
  AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
• Number of Participants With Treatment-emergent Grade 3-4 Abnormalities on Laboratory Test Results [ Time Frame: From screening up to week 24 of post treatment follow--up ]
  Grade 3-4 abnormalities on laboratory test results were defined as: International normalized ratio as 2.1-3.0*upper limit of normal (ULN) for grade 3 and >3.0*ULN for grade 4. Leukocytes as 1.0*10^9-1.5*10^9/L for grade 3 and <1.0*10^9/L for grade 4. Aspartate aminotransferase as 5.1-10.0*ULN for grade 3 and >10.0*ULN for grade 4. Bilirubin (total) as 2.6-5.0*ULN for grade 3 and >5.0*ULN for grade 4. Lipase (total) as 3.1-5.0*ULN for grade 3 and >5.0*ULN for grade 4. Alanine aminotransferase as 5.1-10.0*ULN for grade 3 and >10.0*ULN for grade 4.

Original Secondary Outcome Measures (submitted: January 9, 2014)

• Proportion of treatment-naive subjects with SVR12 [ Time Frame: Post treatment Week 12 ]
  SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12 for the treatment-naive HCV genotype 1 subjects coinfected with HIV on the DCV+SOF 8 -week regimen
• Proportion of treatment-experienced HCV subjects with SVR12 [ Time Frame: Post treatment Week 12 ]
  SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12 for the treatment-experienced HCV genotype 1 subjects coinfected with HIV on the DCV+SOF 12-week regimen
• Proportion of HIV/HCV coinfected subjects, in each treatment arm, with SVR12 [ Time Frame: Post treatment Week 12 ]
  SVR12 defined as HCV RNA < LLOQ TD or TND at follow-up Week 12 without regard to infecting HCV genotype
• Safety measured by deaths and the frequency of serious adverse events (SAEs), discontinuations due to adverse events (AEs), Grade 3/4 AEs, and Grade 3/4 laboratory abnormalities [ Time Frame: Up to EOT (Approximately 8/12 weeks depending on treatment regimen) + 7 days ]
  EOT = End of treatment
• The proportion of subjects coinfected with HIV, in each treatment arm, who achieve HCV RNA < LLOQ-TD/TND [ Time Frame: At Weeks: 1, 2, 4, 6, 8 and 12 (for subjects in the 12-week arm) and EOT; post-treatment Weeks 4 and 24 ]
• The proportion of subjects coinfected with HIV, in each treatment arm, who achieve HCV RNA < LLOQ TND [ Time Frame: At Weeks: 1, 2, 4, 6, 8 and 12 (for subjects in the 12-week arm) and EOT ]
• The proportion of HIV/HCV coinfected subjects, in each treatment arm, with CC or non-CC genotype at the IL28B rs12979860 single nucleotide polymorphisms (SNPs) who achieve SVR12 [ Time Frame: Post treatment Week 12 ]

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

Descriptive Information

• Brief Title: A Phase 3 Study to Evaluate Combination Therapy With Daclatasvir and Sofosbuvir in the Treatment of HIV and Hepatitis C Virus Coinfection.
• Official Title: A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C (Genotype 1, 2, 3, 4, 5, or 6) Subjects Coinfected With Human Immunodeficiency Virus (HIV)
• Brief Summary: A study of the efficacy and safety of the combination of daclatasvir and sofosbuvir in the treatment of hepatitis C virus and HIV coinfection.
• 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

Intervention

• Drug: Daclatasvir
  Other Name: BMS-790052
• Drug: Sofosbuvir

Study Arms

• Experimental: Daclatasvir + Sofosbuvir (Treatment-naive) 12 weeks
  Treatment-naïve participants received daclatasvir 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks
  Interventions:

  • Drug: Daclatasvir
  • Drug: Sofosbuvir
• Experimental: Daclatasvir + Sofosbuvir (Treatment-naive) 8 weeks
  Treatment-naïve participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 8 weeks
  Interventions:

  • Drug: Daclatasvir
  • Drug: Sofosbuvir
• Experimental: Daclatasvir + Sofosbuvir (Treatment-experienced) 12 weeks
  Treatment-experienced participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks
  Interventions:

  • Drug: Daclatasvir
  • Drug: Sofosbuvir

Publications *

• Luetkemeyer AF, McDonald C, Ramgopal M, Noviello S, Bhore R, Ackerman P. 12 Weeks of Daclatasvir in Combination With Sofosbuvir for HIV-HCV Coinfection (ALLY-2 Study): Efficacy and Safety by HIV Combination Antiretroviral Regimens. Clin Infect Dis. 2016 Jun 15;62(12):1489-96. doi: 10.1093/cid/ciw163. Epub 2016 Mar 29.
• Wyles DL, Ruane PJ, Sulkowski MS, Dieterich D, Luetkemeyer A, Morgan TR, Sherman KE, Dretler R, Fishbein D, Gathe JC Jr, Henn S, Hinestrosa F, Huynh C, McDonald C, Mills A, Overton ET, Ramgopal M, Rashbaum B, Ray G, Scarsella A, Yozviak J, McPhee F, Liu Z, Hughes E, Yin PD, Noviello S, Ackerman P; ALLY-2 Investigators. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):714-25. doi: 10.1056/NEJMoa1503153. Epub 2015 Jul 21.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 24, 2015): 238
• Original Estimated Enrollment (submitted: January 9, 2014): 200
• Actual Study Completion Date: January 2015
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Key Inclusion Criteria:

• Patients must be able to understand and agree to/comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
• Patients chronically infected with hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6, as documented by positive HCV RNA at screening
• Patients who are HCV treatment-naive
• Patients who are HCV treatment-experienced and who have had prior anti-HCV therapies discontinued or completed at least 12 weeks prior to screening
• Patients with HCV RNA ≥10,000 IU/mL at screening
• Patients with HIV-1 infection

Key Exclusion Criteria:

• Presence of AIDs-defining opportunistic infections, as defined by the Centers of Disease Control and Prevention, within 12 weeks prior to study entry
• Patients infected with HIV-2
• Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair
• Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to screening
• Documented or suspected hepatocellular carcinoma, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed
• Evidence of decompensated liver disease, including radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy

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: United States

Administrative Information

• NCT Number: NCT02032888
• Other Study ID Numbers: AI444-216
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: August 2015