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

Hepatitis C Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02032888
• Other study ID #: AI444-216
• Status: Completed
• Phase: Phase 3
• First received: January 9, 2014
• Last updated: September 24, 2015
• Start date: February 2014
• Est. completion date: January 2015

Study information

• Verified date: August 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: January 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Hepatitis
• Hepatitis A
• Hepatitis C
• HIV Infections

Intervention

Drug:
• Daclatasvir

• Sofosbuvir

Locations

Country	Name	City	State
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	University Of Colorado	Aurora	Colorado
United States	Digestive Disease Associates, P.A.	Baltimore	Maryland
United States	Pacific Oaks Medical Group	Beverly Hills	California
United States	Binghamton Gastroenterology Associates	Binghamton	New York
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	University Of Cincinnati	Cincinnati	Ohio
United States	Infect. Disease Specialists	Decatur	Georgia
United States	Henry Ford Health System	Detroit	Michigan
United States	Midway Immunology And Research Center	Fort Pierce	Florida
United States	Tarrant County Inf Dis Assoc	Fort Worth	Texas
United States	Cure C Consortium	Houston	Texas
United States	University Of Texas Health Science Center At Houston	Houston	Texas
United States	Indiana University Health - University Hospital	Indianapolis	Indiana
United States	Va Long Beach Healthcare System	Long Beach	California
United States	Anthony M. Mills Md Inc	Los Angeles	California
United States	Jeffrey Goodman Special Care Clinic	Los Angeles	California
United States	Peter J Ruane Md Inc	Los Angeles	California
United States	Johns Hopkins University	Lutherville	Maryland
United States	University Of Miami Schiff Center For Liver Diseases	Miami	Florida
United States	Clinical Research Centers Of America	Murray	Utah
United States	Icahn School Of Medicine At Mount Sinai	New York	New York
United States	Orlando Immunology Center	Orlando	Florida
United States	Oregon Health Science Univ	Portland	Oregon
United States	The Miriam Hospital	Providence	Rhode Island
United States	University Gastroenterology	Providence	Rhode Island
United States	Mcguire D V A M C	Richmond	Virginia
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Precision Research Institute, Llc	San Diego	California
United States	Ucsd Antiviral Research Center (Avrc)	San Diego	California
United States	University Of California San Francisco	San Francisco	California
United States	Southwest Care Center	Sante Fe	New Mexico
United States	Harborview Medical Center	Seattle	Washington
United States	Healthcare Research Consultants	Tulsa	Oklahoma
United States	Capital Medical Associates	Washington	District of Columbia
United States	Medstar Washington Hospital Center	Washington	District of Columbia
United States	Whitman Walker Health	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Genotype 1 Hepatitis C Virus (HCV)-Infected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)	SVR12 was defined as HCV RNA	At follow-up Week 12	No
Secondary	Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)	SVR12 was defined as HCV RNA	At follow-up Week 12	No
Secondary	Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-experienced Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)	SVR12 was defined as HCV RNA	At follow-up Week 12	No
Secondary	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)	SVR12 was defined as HCV RNA levels	At follow-up Week 12	No
Secondary	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	Participants with hepatitis C virus CV) levels to be	Week 1, 2, 4, 6, 8, 12, End of treatment, and follow-up Week 4 and 24	No
Secondary	Percentage of Participants Coinfected With Hepatitis C Virus/HIV Who Achieved HCV RNA Levels<Lower Limit of Quantitation (LLOQ), Target Not Detected (TND)	Participants with HCV RNA levels	At Weeks 1, 2, 4, 6, 8, and 12 and at End of Treatment	No
Secondary	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)	SVR is defined as hepatitis C virus RNA	At Follow-up Week 12	No
Secondary	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	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.	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)	Yes
Secondary	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	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.	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.	Yes
Secondary	Number of Participants With Treatment-emergent Grade 3-4 Abnormalities on Laboratory Test Results	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.	From screening up to week 24 of post treatment follow--up	Yes

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