Efficacy and Safety Study of Pegylated Interferon Lambda-1a With Ribavirin and Daclatasvir, to Treat naïve Subjects With Chronic HCV Genotypes 1, 2, 3, and 4 Who Are Co-infected With HIV

Chronic Hepatitis C Infection Clinical Trial

— DIMENSION  

Official title:

Phase 3 Open Label Study Evaluating the Efficacy and Safety of Pegylated Interferon Lambda-1a, in Combination With Ribavirin and Daclatasvir, for Treatment of Chronic HCV Infection With Treatment naïve Genotypes 1, 2, 3 or 4 in Subjects Co-infected With HIV

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01866930
• Other study ID #: AI452-032
• Secondary ID: 2012-003280-22
• Status: Terminated
• Phase: Phase 3
• Start date: July 11, 2013
• Est. completion date: August 27, 2015

Study information

• Verified date: February 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate Sustained Virologic Response at post treatment Week 12 (SVR12)following treatment with Lambda/RBV/DCV in chronic HCV GT-1, -2, -3 or -4 subjects co-infected with HIV-1

Description:

Study Classification: Safety/Efficacy and Pharmacokinetics/dynamics

GT=genotype

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 453
• Est. completion date: August 27, 2015
• Est. primary completion date: August 27, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HCV Genotype-1, -2, -3 or -4 treatment naïve;

• HCV RNA =10,000 IU/mL at screening;

• HIV-1 infection [(approximately 200 subjects receiving HAART, approximately 100 subjects not receiving highly active antiretroviral therapy (HAART)];

• For subjects receiving HAART, HIV RNA must be below <40 copies/mL at screening and <200 copies/mL for at least 8 weeks prior to screening;

• CD4 cell count at screening must be =100 cells/µL if receiving HAART or =350 cells/µL if not receiving HAART)

• Seronegative for Hepatitis B Surface Antigen (HBsAg)

• Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive. BMI=weight (kg)/[height (m)]2 at screening;

• Subjects with compensated cirrhosis are permitted, but the number of subjects will be capped at approximately 30%. If a subject does not have cirrhosis, a liver biopsy within 3 years prior to enrollment is required to demonstrate the absence of cirrhosis. If cirrhosis is present, any prior liver biopsy is sufficient. Fibroscan® or FibroTest are acceptable if performed within 1 year prior to treatment in countries where liver biopsy is not required prior to treatment and where non-invasive imaging tests are approved for staging of liver disease

• Subjects with mild to moderate hemophilia as defined as:

1. Mild-factor level activity of 6-4% OR

2. Moderate defined as factor level activity of 1-5%

Exclusion Criteria:

• Any evidence of liver disease other than chronic HCV;

• Subjects infected with human immunodeficiency virus (HIV-2);

• Diagnosed or suspected hepatocellular carcinoma;

• Decompensated liver disease;

• Presence of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 weeks prior to study entry (AIDS-defining opportunistic infections as defined by the CDC, (CDC, JAMA 1993 Feb 10;269(6):729-30)

• Laboratory values: ANC <1.5 x 109 cells/L (<1.2 x 109 cells/L for Blacks), platelet count <90 x 109 cells/L, hemoglobin <11 g/dL for females, hemoglobin <12 g/dL for males;

• Subjects (receiving HAART) who had first initiated anti-retroviral therapy within last 8 weeks prior to Day 1; however, if changes are required to a subject's HAART regimen to meet the requirements of the protocol, these changes are allowed at the screening visit. Subjects should wait a minimum of 1 month prior to Day 1 after a repeat of HIV viral load has been confirmed, <40 copies/mL

• Subjects on Zidovudine (AZT), Didanosine (ddI), or Stavudine (d4T);

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

• Subjects with severe hemophilia (defined as <1% factor activity level)

Related Conditions & MeSH terms

• Chronic Hepatitis C Infection
• Hepatitis C
• Hepatitis C, Chronic
• Infections

Intervention

Biological:
• Pegylated Interferon Lambda-1a

Drug:
• Daclatasvir (DCV)

• Ribasphere (RBV)

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires, Bs As	Buenos Aires
Argentina	Local Institution	Mar Del Plata	Buenos Aires
Argentina	Local Institution	Quilmes	Buenos Aires
Belgium	Local Institution	Antwerpen
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Bruxelles
Canada	University Of Alberta Hospitals	Edmonton	Alberta
Canada	Hamilton Health Sciences, Mcmaster Site	Hamilton	Ontario
Canada	Mcgill University Health Centre (Muhc) Montreal Chest Institute	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Ottawa Hospital General Campus	Ottawa	Ontario
Canada	St Pauls Hospital	Vancouver	British Columbia
Canada	Vancouver Id Reserach & Care Centre Society	Vancouver	British Columbia
France	Local Institution	Le Kremlin Bicetre
France	Local Institution	Lyon
France	Local Institution	Paris
France	Local Institution	Paris
France	Local Institution	Pessac Cedex
Germany	Local Institution	Berlin
Germany	Local Institution	Bonn
Germany	Local Institution	Bonn
Germany	Local Institution	Hamburg
Italy	Local Institution	Antella (fi)
Italy	Local Institution	Brescia
Italy	Local Institution	Milano
Italy	Local Institution	Monza
Italy	Local Institution	Roma
Mexico	Local Institution	Ciudad Juarez	Chihuahua
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Leon	Guanajuato
Mexico	Local Institution	Mexico	Distrito Federal
Poland	Local Institution	Lodz
Poland	Local Institution	Wroclaw
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	Volgograd
Spain	Local Institution	Barcelona
Spain	Local Institution	Cartagena (Murcia)
Spain	Local Institution	Donosti-San Sebastian
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
United Kingdom	Local Institution	Brighton
United Kingdom	Local Institution	London
United Kingdom	Local Institution	London
United Kingdom	Local Institution	London
United Kingdom	Local Institution	London	Greater London
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Emory Hospital Midtown Infectious Disease Clinic	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	University Of Colorado Denver	Aurora	Colorado
United States	University Of Colorado Denver & Hospital	Aurora	Colorado
United States	Mercy Medical Center	Baltimore	Maryland
United States	Ut Southwestern Medical Center	Dallas	Texas
United States	Duke Clinical Research Institute	Durham	North Carolina
United States	Yale University	New Haven	Connecticut
United States	Orlando Va Medical Center	Orlando	Florida
United States	Inland Empire Liver Foundation	Rialto	California
United States	Kaiser Permanente Medical Center	San Francisco	California
United States	University Of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  France,  Germany,  Italy,  Mexico,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)	SVR12 was defined as HCV RNA less than lower limit of quantification (< LLOQ) (25 IU/mL; target detected or not detected) at follow-up week 12.	Follow-up week 12
Secondary	Number of Participants With Rapid Virologic Response (RVR) and Extended Rapid Virologic Response (eRVR)	RVR is defined as HCV RNA < LLOQ target not detected at Week 4 and eRVR defined as HCV RNA < LLOQ target not detected at Weeks 4 and 12	Treatment weeks 4 and 12
Secondary	Number of Subjects With Sustained Virologic Response at Post-treatment Week 24 (SVR24)	SVR24 was defined as HCV RNA < LLOQ (25 IU/mL; target detected or not detected) at 24 weeks post treatment.	Follow-up week 24
Secondary	Number of Participants With Treatment Emergent Cytopenic Abnormalities	All treated participants were monitored for treatment emergent cytopenic abnormalities (anemia as defined by hemoglobin (Hb) < 10 g/dL, and/or neutropenia as defined by absolute neutrophil count (ANC) < 750 mm3 and/or thrombocytopenia as defined by platelets < 50,000/mm3) during the treatment period (Weeks 1, 2, 4, 6, 8, 12, 20, and 24, and at Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits).	After Day 1 to end of treatment; up to Weeks 24 or 48
Secondary	Number of Participants With On-treatment IFN-associated Flu-like or Musculoskeletal Symptoms	All treated participants were monitored for IFN-associated Flu-like and Musculoskeletal symptoms. Flu-like symptoms were defined as pyrexia, chills, or pain. Musculoskeletal symptoms were defined as arthralgia, myalgia, or back pain. Subjects were monitored throughout the treatment period during the treatment period (After day 1 up to week 24, or After day 1 up to week 48 for subjects requiring those visits).	After Day 1 to end of treatment; up to Weeks 24 or 48
Secondary	Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs)	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that. at any dose, results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.	After Day 1 to end of treatment; up to Weeks 24 or 48
Secondary	Number of Participants With Treatment-emergent Grade 3/4 Lab Abnormalities	Grade 3/4 treatment-emergent lab abnormalities that occurred in >=5% of subjects in either cohort are reported. The analysis included all treated subjects up to the end of the treatment period (Day 1 to week 24, or Day 1 to week 48 for subjects requiring those visits). Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. AST = Aspartate aminotransferase, ALT = Alanine aminotransferase.	After Day 1 to end of treatment; up to Weeks 24 or 48
Secondary	Mean Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment	All treated participants were monitored for change in Absolute CD4 T Lymphocyte count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants is reported in Cells/µL.	Day 1 to end of treatment; up to week 24 or week 48
Secondary	Mean Percent Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment	All treated participants were monitored for percent change in CD4 T Lymphocyte count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants.	Day 1 to end of treatment; up to week 24 or week 48
Secondary	Mean Change in Total Lymphocyte Count From Baseline to End of Treatment	All treated participants were monitored for change in Total Lymphocyte Count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants is reported in Cells/µL.	Day 1 to end of treatment; up to week 24 or week 48
Secondary	Mean Percent Change in Total Lymphocyte Count From Baseline to End of Treatment	All treated participants were monitored for percent change in Total Lymphocyte Count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants.	Day 1 to end of treatment; up to week 24 or week 48
Secondary	Mean Change in Platelet Count From Baseline to End of Treatment	All treated participants were monitored for change in Platelet Count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants (units of measurement = x10^9 cells/L).	Day 1 to end of treatment; up to week 24 or week 48
Secondary	Mean Percent Change in Platelet Count From Baseline to End of Treatment	All treated participants were monitored for percent change in Platelet Count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants.	Day 1 to end of treatment; up to week 24 or week 48

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