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Role of Pegylated Interferon in Combination With DAAs to Cure Hepatitis C As Soon As Possible - Hepatitis C [ASAP-C]

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ClinicalTrials.gov Identifier: NCT03480932
Recruitment Status : Completed
First Posted : March 29, 2018
Last Update Posted : March 15, 2019
Sponsor:
Collaborators:
National Institute on Drug Abuse (NIDA)
YR Gaitonde Centre for AIDS Research and Education
Information provided by (Responsible Party):
Johns Hopkins Bloomberg School of Public Health

Brief Summary:
The primary objective of this pilot trial is to compare the efficacy, measured as sustained virologic response (SVR) at least 12 weeks after completion of therapy, across three study regimens/delivery modalities: Arm 1 - 4 weeks of sofosbuvir (SOF) + daclatasvir (DAC) + pegylated interferon alfa-2a (PEG) delivered using directly observed therapy (DOT); Arm 2 - 12 weeks of SOF+DAC delivered using DOT; and Arm 3 - 12 weeks of SOF+DAC delivered as per standard of care (monthly dispensation with no DOT). Secondary objectives are 1)To compare the cost per SVR for each of the three study arms; 2) To compare adherence among persons across the three study arms; 3) To evaluate the safety, tolerability and acceptability of treatment in the three arms.

Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Drug: Sofosbuvir Drug: Daclatasvir Drug: Pegylated Interferon alfa-2a Phase 2 Phase 3

Detailed Description:

This will be a non-blinded randomized clinical trial with 150 participants randomized at a 1:1:1 allocation ratio to one of three treatment arms.

Arm 1: Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) for 4 weeks with a field-based DOT approach

Arm 2: Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with a field-based DOT approach

Arm 3: Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with standard of care dispensation (4 monthly doses)

Pegylated-interferon alfa-2a (PEG) will be delivered subcutaneously once weekly. Sofosbuvir (SOF) and Daclatasvir (DAC) will be taken orally once daily for the entire study period.

The study will take place at the YR Gaitonde Centre for AIDS Education (YRG) and Johns Hopkins University (JHU) Collaborative Integrated Care Center (YRG-JHU ICC) located within the premises of the Chattisgarh Institute of Medical Sciences (CIMS) in Bilaspur in the state of Chattisgarh, India.

Participants will be recruited from the YRG-JHU ICC in Bilaspur, which currently has 514 registered HCV antibody positive clients. The Bilaspur ICC is in the Chattisgarh Institute for Medical Sciences (CIMS).

The primary outcome will be sustained virologic response (SVR12). Secondary outcomes include cost per SVR12, adherence, safety and tolerability.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Role of Pegylated Interferon in Combination With Direct Acting Antivirals (DAAs) to Cure Hepatitis C As Soon As Possible (ASAP) - Hepatitis C [ASAP-C]
Actual Study Start Date : February 2, 2018
Actual Primary Completion Date : November 2, 2018
Actual Study Completion Date : November 2, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: SOF+DAC+PEG
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) for 4 weeks with a field-based DOT approach
Drug: Sofosbuvir
Direct acting antiviral agent used for the treatment of hepatitis C
Other Names:
  • Sovaldi
  • Hepcvir
  • MyHep
  • Hepcinat
  • Resof
  • SoviHep

Drug: Daclatasvir
Direct acting antiviral agent used for the treatment of hepatitis C
Other Names:
  • Daklinza
  • Natdac
  • Daclahep
  • Dacihep
  • Hepdac
  • Mydekla

Drug: Pegylated Interferon alfa-2a
Antiviral agent used for the treatment of hepatitis C
Other Names:
  • Pegasys
  • Taspiance

Active Comparator: SOF+DAC, DOT
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with a field-based DOT approach
Drug: Sofosbuvir
Direct acting antiviral agent used for the treatment of hepatitis C
Other Names:
  • Sovaldi
  • Hepcvir
  • MyHep
  • Hepcinat
  • Resof
  • SoviHep

Drug: Daclatasvir
Direct acting antiviral agent used for the treatment of hepatitis C
Other Names:
  • Daklinza
  • Natdac
  • Daclahep
  • Dacihep
  • Hepdac
  • Mydekla

Active Comparator: SOF+DAC, standard
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with standard of care dispensation (4 monthly doses)
Drug: Sofosbuvir
Direct acting antiviral agent used for the treatment of hepatitis C
Other Names:
  • Sovaldi
  • Hepcvir
  • MyHep
  • Hepcinat
  • Resof
  • SoviHep

Drug: Daclatasvir
Direct acting antiviral agent used for the treatment of hepatitis C
Other Names:
  • Daklinza
  • Natdac
  • Daclahep
  • Dacihep
  • Hepdac
  • Mydekla




Primary Outcome Measures :
  1. SVR12 [ Time Frame: 16 or 24 weeks ]
    Sustained virologic response 12 weeks after treatment is completed (SVR12) as assessed by undetectable HCV RNA measured 12 weeks after treatment completion


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 16 or 24 weeks ]
    Number of participants with treatment-related serious adverse events by laboratory tests and physician examination

  2. Cost per SVR12 [ Time Frame: 16 or 24 weeks ]
    The total costs of treatment + monitoring tests + additional costs associated with the intervention (e.g., DOT) divided by the number who achieve SVR12

  3. Medication adherence [ Time Frame: 4 or 12 weeks ]
    Adherence to medication regimen defined using a combination of the biometric data for Arms 1 and 2 and self-report and pill counts for Arm 3



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to provide written informed consent
  2. Age ≥ 18 years
  3. Documented evidence of chronic HCV infection (HCV RNA positive)
  4. Participant is a resident of Bilaspur and can provide locator information that can be verified by one of the study staff
  5. If participant is co-infected with HIV, he/she must have a cluster of differentiation 4 (CD4) > 350 cells/mm3 and be either: 1) antiretroviral therapy (ART) naïve or 2) on ART be on a tenofovir-containing regimen. If a subject's CD4 drops below 350 cells/μl (current threshold for HIV treatment in India), he/she will be able to initiate ART but we will ensure that the subject starts on a tenofovir-containing regimen, which is currently the standard for persons newly initiating ART in India.
  6. Subjects must have the following laboratory parameters at screening:

    1. alanine aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN)
    2. aspartate aminotransferase (AST) ≤ 10 x ULN
    3. Hemoglobin ≥ 10 g/dl for male and 9 g/dl for female subjects
    4. International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
    5. Albumin ≥ 3 g/dl
    6. Direct bilirubin ≤ 1.5 x ULN
    7. Creatinine clearance ≥ 30 ml/min as calculated by the Cockcroft-Gault Equation
    8. Alpha fetoprotein < 50 ng/ml
    9. Absolute neutrophil count (ANC) ≥ 1,500/μL
    10. Platelets ≥ 90,000/μL
    11. Thyroid stimulating hormone (TSH) ≤ ULN
    12. FIB-4 <3.25 (Participants with a FIB-4 >3.25 will be referred to the medical gastroenterology department for further assessment for cirrhosis. If cirrhosis is ruled out by medical gastroenterology, participants can be rescreened for the study.
  7. A female subject is eligible to enroll in the study if it is confirmed that she is:

    1. Not pregnant or nursing
    2. Not of childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal women > 50 years of age with cessation (for ≥12 months) of previously occurring menses)
    3. Of childbearing potential (i.e., women who have not had a hysterectomy, both ovaries removed or medically documented ovarian failure). [NOTE: Women ≤50 years of age with amenorrhea will be considered to be of childbearing potential.] These women must have a negative urine pregnancy test at screening and a negative urine pregnancy test on the Baseline /Day 1 visit prior to randomization and agree to one of the following modes of contraception for the duration of treatment and 12 weeks thereafter.

      • Complete abstinence from intercourse. Periodic abstinence (e.g., calendar, ovulation, sumptothermal, post-ovulation methods) is NOT permitted.

    or

    i. Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from 3 weeks prior to Baseline/Day 1 until the end of treatment. Women of childbearing potential must not rely on hormone-containing contraceptives as a form of birth control during the study. Female subjects using a hormone containing contraceptive prior to screening may continue their contraceptive regimen in addition to the study specified methods of birth control.

    • intrauterine device (IUD) with a documented failure rate of less than 1% per year
    • female barrier method: cervical cap or diaphragm with spermicidal agent
    • tubal sterilization
    • vasectomy in male partner
  8. Subjects must be of generally good health as determined by the investigator.
  9. Subjects must be able to comply with the dosing instructions for study drug administration and be willing to complete the study schedule of assessments.

Exclusion Criteria:

  1. Pregnant or nursing female
  2. Current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage, model for end-stage liver disease (MELD)<12)
  3. Prior treatment for hepatitis C virus infection
  4. Infection with hepatitis B virus (HBsAg positive)
  5. Chronic use of systematically administered immunosuppressive agents (e.g., prednisone equivalent >10 mg/day)
  6. Use of any prohibited concomitant medications within 28 days of the Baseline/Day 1 visit.
  7. Contraindications to PEG
  8. Known hypersensitivity to the metabolites or formulation excipients of PEG (for Arm 1 subjects)
  9. Active significant psychiatric condition(s) including severe depression, severe bipolar disorder and schizophrenia. Other psychiatric disorders are permitted if the condition is well controlled with a stable treatment regimen for ≥ 1 year from screening, or inactive for ≥ 1 year from screening.
  10. Presence of autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, psoriasis of greater than mild severity)
  11. History of clinical significant retinal disease
  12. Clinical evidence of cirrhosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03480932


Locations
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India
YR Gaitonde Centre for AIDS Education and Johns Hopkins University Collaborative Integrated Care Center (YRG-JHU ICC)
Bilaspur, Chhattisgarh, India, 495009
Sponsors and Collaborators
Johns Hopkins Bloomberg School of Public Health
National Institute on Drug Abuse (NIDA)
YR Gaitonde Centre for AIDS Research and Education
Investigators
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Principal Investigator: Shruti Mehta, PhD, MPH Johns Hopkins Bloomberg School of Public Health

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Responsible Party: Johns Hopkins Bloomberg School of Public Health
ClinicalTrials.gov Identifier: NCT03480932     History of Changes
Other Study ID Numbers: R01DA026727 ( U.S. NIH Grant/Contract )
R01DA026727 ( U.S. NIH Grant/Contract )
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Johns Hopkins Bloomberg School of Public Health:
directly observed therapy
sofosbuvir
daclatasvir
pegylated interferon
resource-limited setting
Additional relevant MeSH terms:
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Interferon-alpha
Antiviral Agents
Interferon alpha-2
Antineoplastic Agents
Anti-Infective Agents
Physiological Effects of Drugs
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Interferons
Sofosbuvir
Peginterferon alfa-2a
Immunologic Factors