Safety and Efficacy Study of Daclatasvir (BMS-790052) Plus Pegylated Interferon-Alfa 2a and Ribavirin in Patients Coinfected With Untreated Hepatitis C Virus and HIV Virus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01471574
First received: November 4, 2011
Last updated: December 22, 2015
Last verified: December 2015
Results First Received: August 18, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hepatitis C, Genotype 1
Interventions: Drug: Daclatasvir
Drug: Ribavirin
Drug: PEG-Interferon alfa 2a

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 84 sites in 13 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 549 participants enrolled, 301 were randomized to receive treatment. Of the 248 participants who were not randomized, 204 no longer met study criteria, and 44 discontinued due to other reasons.

Reporting Groups
  Description
Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing <75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
HAART: Daclatasvir, 60 mg Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing <75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
HAART: Daclatasvir, 30 mg + 60 mg Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received 2 daclatasvir tablets (1x30 mg and 1x60 mg), orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing <75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Non-­HAART Therapy Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing <75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.

Participant Flow for 2 periods

Period 1:   Treatment Period
    Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg     HAART: Daclatasvir, 60 mg     HAART: Daclatasvir, 30 mg + 60 mg     Non-­HAART Therapy  
STARTED     132     39     106     24  
COMPLETED     101     29     82     21  
NOT COMPLETED     31     10     24     3  
Lack of Efficacy                 12                 4                 14                 1  
Adverse Event                 7                 3                 6                 1  
Withdrawal by Subject                 5                 1                 1                 0  
Patient Requested Discontinue Study drug                 4                 0                 1                 1  
Lost to Follow-up                 1                 2                 2                 0  
Patient no Longer Meets Study Criteria                 1                 0                 0                 0  
Not specified                 1                 0                 0                 0  

Period 2:   Follow-up Period
    Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg     HAART: Daclatasvir, 60 mg     HAART: Daclatasvir, 30 mg + 60 mg     Non-­HAART Therapy  
STARTED     121     34     102     24  
COMPLETED     114     32     95     21  
NOT COMPLETED     7     2     7     3  
Withdrawal by Subject                 3                 0                 3                 1  
Lost to Follow-up                 4                 1                 3                 2  
Death                 0                 0                 1                 0  
Follow-up no longer required                 0                 1                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of study therapy.

Reporting Groups
  Description
Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing <75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
HAART Therapy: Daclatasvir, 60 mg Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing <75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
HAART: Daclatasvir, 30 mg + 60 mg Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received 2 daclatasvir tablets (1x30 mg and 1x60 mg), orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing <75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Non-HAART Therapy: Daclatasvir, 60 mg Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing <75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Total Total of all reporting groups

Baseline Measures
    Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg     HAART Therapy: Daclatasvir, 60 mg     HAART: Daclatasvir, 30 mg + 60 mg     Non-HAART Therapy: Daclatasvir, 60 mg     Total  
Number of Participants  
[units: participants]
  132     39     106     24     301  
Age  
[units: years]
Mean (Standard Deviation)
  47  (9.72)     47.9  (9.03)     46.5  (9.42)     36  (9.02)     46.1  (9.90)  
Age, Customized  
[units: participants]
         
Younger than 65 years     125     39     104     24     292  
65 years and older     7     0     2     0     9  
Gender  
[units: participants]
         
Female     27     7     27     11     72  
Male     105     32     79     13     229  



  Outcome Measures
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1.  Primary:   Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)   [ Time Frame: Follow-up Week 12 ]

2.  Secondary:   Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND)   [ Time Frame: Week 1, 2, 4, 6, 8, 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24 ]

3.  Secondary:   Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND)   [ Time Frame: Week 1, 2, 4, 6, 8, and 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24 ]

4.  Secondary:   Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL   [ Time Frame: End of treatment (up to Week 48) ]

5.  Secondary:   Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene   [ Time Frame: Follow-up Week 12 ]

6.  Secondary:   Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation   [ Time Frame: From Day 1 to 7 days post last dose of study treatment (up to Week 48) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com



Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01471574     History of Changes
Other Study ID Numbers: AI444-043
2011-003067-30 ( EudraCT Number )
Study First Received: November 4, 2011
Results First Received: August 18, 2015
Last Updated: December 22, 2015
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Spain: Spanish Agency of Medicines
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Brazil: National Health Surveillance Agency
Brazil: National Committee of Ethics in Research
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica