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Trial record 1 of 1 for:    a5329
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Evaluating the Safety and Effectiveness of Interferon-Free Treatment of Hepatitis C Virus Infection in HIV-Coinfected Adults on Antiretroviral Therapy (C_ASCENT)

This study is currently recruiting participants.
Verified October 2017 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02194998
First Posted: July 21, 2014
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose
HIV and hepatitis C virus (HCV) infection are diseases that share the same risk factors and routes of transmission. For this reason, many people infected with HIV are also infected with HCV. Interferon (IFN) is a drug used to treat HCV; however, in people coinfected with HIV and HCV, IFN treatment often does not work well and can cause unwanted side effects. The purpose of this study is to evaluate the safety, tolerability, and effectiveness of IFN-free HCV treatment in HIV/HCV coinfected adults who are taking antiretroviral (ARV) therapy.

Condition Intervention Phase
HIV Infections Drug: Paritaprevir/ritonavir/ombitasvir (PTV/r/OBT) Drug: Dasabuvir (DSV) Drug: Ribavirin (RBV) Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Interferon-Free Therapy for Chronic Hepatitis C Virus Genotype 1 Infection in Participants With HIV-1 Coinfection Receiving Concurrent Antiretroviral Therapy (C_ASCENT)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Evaluation of sustained virologic response (SVR)12 [ Time Frame: At least 12 weeks post HCV treatment discontinuation (possibly through Week 36) ]
    Responders will be those whose HCV RNA is less than the assay lower limit of quantification (LLOQ). For those whose HCV early responses prior to SVR12 evaluation meet the guidelines for HCV virologic failure (VF), their SVR12 outcome will be defined as non-response.

  • Evaluation of serious adverse events (SAEs) as defined by International Conference on Harmonisation (ICH) criteria [ Time Frame: Measured through Week 48 ]
  • Number of premature HCV study treatment discontinuations due to any reason other than HCV VF [ Time Frame: Measured through Week 48 ]
  • Presence of signs/symptoms Grade 3 or higher during HCV study treatment and up to 30 days following HCV study treatment discontinuation [ Time Frame: Measured through Week 48 ]
  • Number of diagnoses leading to HCV study treatment or HIV-1 antiretroviral (ARV) discontinuation [ Time Frame: Measured through Week 48 ]
  • Presence of laboratory abnormalities Grade 3 or higher during HCV study treatment and up to 30 days following HCV study treatment discontinuation [ Time Frame: Measured through Week 48 ]

Secondary Outcome Measures:
  • Measurement of HIV-1 VF as defined in the protocol [ Time Frame: Measured through Week 48 ]
  • Presence of genotypic mutations conferring major resistance to any HIV-1 protease inhibitor (PI) at time of HIV-1 RNA VF (or confirmation of HIV-1 RNA VF) [ Time Frame: Measured through Week 48 ]
  • Measurement of soluble CD14 (sCD14) levels [ Time Frame: Measured through Week 36 ]
  • Measurement of interferon gamma-induced protein 10 (IP10) levels as biomarkers of immune activation [ Time Frame: Measured through Week 36 ]
  • Frequency of HCV mutations conferring resistance to any component of the HCV treatment regimen in the first sample with a HCV viral load (VL) greater than 1000 IU/mL among the subset of participants who are non-responders for SVR12 [ Time Frame: Measured through Week 36 ]
  • Measurement of SVR24 in 12- and 24-week cohorts [ Time Frame: Measured through Week 48 ]

Estimated Enrollment: 100
Study Start Date: August 2015
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A
Participants in Cohort A will receive the following medications for 24 weeks: paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV) (RBV for participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV).
Drug: Paritaprevir/ritonavir/ombitasvir (PTV/r/OBT)
PTV/r/OBT: 150/100/25 mg (two 75/50/12.5 mg fixed-dose combination tablets) orally once a day
Drug: Dasabuvir (DSV)
DSV: 250 mg orally twice a day
Drug: Ribavirin (RBV)
RBV: 1,000 or 1,200 mg (weight-based) dosed in two divided doses orally twice a day (participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV)
Experimental: Cohort B
Participants in Cohort B will receive the following medications for 12 weeks: paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV) (RBV for participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV).
Drug: Paritaprevir/ritonavir/ombitasvir (PTV/r/OBT)
PTV/r/OBT: 150/100/25 mg (two 75/50/12.5 mg fixed-dose combination tablets) orally once a day
Drug: Dasabuvir (DSV)
DSV: 250 mg orally twice a day
Drug: Ribavirin (RBV)
RBV: 1,000 or 1,200 mg (weight-based) dosed in two divided doses orally twice a day (participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV)
Experimental: Cohort C
Participants in Cohort C will receive the following medications for 24 weeks: paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV) (RBV for participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV).
Drug: Paritaprevir/ritonavir/ombitasvir (PTV/r/OBT)
PTV/r/OBT: 150/100/25 mg (two 75/50/12.5 mg fixed-dose combination tablets) orally once a day
Drug: Dasabuvir (DSV)
DSV: 250 mg orally twice a day
Drug: Ribavirin (RBV)
RBV: 1,000 or 1,200 mg (weight-based) dosed in two divided doses orally twice a day (participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV)
Experimental: Cohort D
Participants in Cohort D will receive the following medications for 12 weeks: paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV) (RBV for participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV).
Drug: Paritaprevir/ritonavir/ombitasvir (PTV/r/OBT)
PTV/r/OBT: 150/100/25 mg (two 75/50/12.5 mg fixed-dose combination tablets) orally once a day
Drug: Dasabuvir (DSV)
DSV: 250 mg orally twice a day
Drug: Ribavirin (RBV)
RBV: 1,000 or 1,200 mg (weight-based) dosed in two divided doses orally twice a day (participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV)

Detailed Description:

This study will evaluate the safety, tolerability, and effectiveness of a combination of drugs to treat HCV in adults who are coinfected with HIV and HCV. The three drugs are paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV). RBV will be given to participants with HCV genotype 1a only; participants with HCV genotype 1b will not receive RBV.

This study will enroll HCV genotype 1a or 1b and HIV-1 coinfected participants (HCV treatment-naïve or HCV treatment-experienced) who are on a concurrent integrase inhibitor (INI)-based (raltegravir [RAL] or dolutegravir [DTG]) or protease inhibitor (PI)-based (darunavir [DRV] or atazanavir [ATV]) ART regimen. (The ART regimens will not be provided by the study.) The participants will be assigned to one of four cohorts (Cohorts A, B, C, and D). Participants in Cohorts A and B will be on INI-based ART; participants in Cohorts C and D, on PI-based ART. For each group, the study will proceed in two steps: Step 1: on-HCV treatment and Step 2: post-HCV treatment follow-up. Participants in Cohorts A and C will receive the HCV drugs for 24 weeks; participants in Cohorts B and D, for 12 weeks.

Total study duration will be up to 48 weeks. During Step 1 (on-HCV treatment), all participants will have study visits at Weeks 2, 4, 6, 8, 10, and 12. Participants in Cohorts A and C will have additional Step 1 study visits at Weeks 16, 20, and 24.

All participants will have Step 2 (post-treatment follow-up) study visits 4, 12, and 24 weeks after registration to Step 2. Participants in Cohorts B and D will have an additional Step 2 visit 36 weeks after registration to Step 2.

All study visits will include a brief physical exam and blood collection. Select study visits will include pregnancy testing for participants able to become pregnant, an electrocardiogram (EKG), an IFN gamma-induced protein 10 (IP-10) test, and collection of plasma samples.

Some participants may take part in two optional substudies. In one substudy, participants will attend two study visits at entry/Day 0 and Week 4 for 12-hour intensive pharmacokinetic (PK) sampling. In another substudy, participants will undergo liver biopsies at two time points and PK sampling.

  Eligibility

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.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Step 1 Inclusion Criteria:

  • Men and women age greater than or equal to 18 to less than or equal to 70 years at study entry.
  • Body mass index (BMI) from greater than or equal to 18 to less than 38 kg/m^2 within 42 days of study entry. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
  • HIV-1 infection, documented by any licensed rapid HIV-1 test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV-1 and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load. More information on this criterion can be found in the protocol.
  • CD4+ cell count greater than or equal to 200 cells/uL and CD4+ cell percentage greater than or equal to 14% within 42 days of study entry at any U.S. laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification
  • On a stable, qualifying ART regimen for at least 8 weeks prior to entry. More information on this criterion can be found in the protocol.
  • HIV-1 RNA less than 50 copies/mL for at least 6 months prior to study entry by any U.S. laboratory that has a CLIA certification or its equivalent. HIV-1 RNA testing must have been performed at least once during the 6 months prior to study entry. More information on this criterion can be found in the protocol.
  • Presence of chronic HCV infection defined as positive for anti-HCV antibody or HCV RNA at least 6 months before screening, and positive for HCV RNA at the time of screening; OR positive for HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection any time prior to study entry
  • HCV treatment-naïve or unsuccessful treatment with pegylated or standard IFN alfa with or without RBV. NOTE: No prior exposure to HCV NS3/4A PI (including but not limited to TVR, BOC, simeprevir), NS5A inhibitors (including but not limited to daclatasvir or ledipasvir), NS5B NNI or NI inhibitors (including but not limited to sofosbuvir) is allowed.
  • HCV genotype 1a or 1b infection confirmed by testing at the A5329 VSL Quest Diagnostics. More information on this criterion can be found in the protocol.
  • Serum HCV RNA greater than 10,000 IU/mL obtained within 42 days prior to study entry by any assay performed by the designated A5329 VSL Quest Diagnostics
  • The following laboratory values obtained within 42 days prior to study entry.

    • Absolute neutrophil count (ANC) greater than or equal to 750/mm^3
    • Hemoglobin greater than or equal to 12 g/dL for men and greater than or equal to 11 g/dL for women
    • Platelet count greater than or equal to 90,000/mm^3
    • International normalized ratio (INR) less than or equal to 1.5.
    • Participants with known inherited bleeding disorder and INR greater than or equal to 1.5 may be enrolled.
    • Calculated creatinine clearance (CrCl) using Cockcroft-Gault method greater than or equal to 60 mL/min
    • Alanine aminotransferase (ALT) less than or equal to 7 times the upper limit of the normal range (ULN)
    • Aspartate aminotransferase (AST) less than or equal to 7 times the ULN range
    • Total bilirubin less than 3 mg/dL for participants not on ATV and less than 6 mg/dL for participants on ATV
    • Direct bilirubin less than or equal to 1.5 times the ULN
    • Albumin greater than or equal to 3.5 g/dL
    • Serum alfa-fetoprotein (AFP) less than or equal to 100 ng/mL
  • Classification of liver disease as non-cirrhotic prior to study entry according to specified criteria. See the protocol for more information.
  • Females of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months [i.e., who have had menses within 24 months prior to study entry, or women who have not undergone surgical sterilization, specifically hysterectomy, tubal ligation, and/or bilateral oophorectomy]) must have a negative serum or urine pregnancy test with a sensitivity of less than or equal to 25 mIU/mL within 42 days prior to study entry by any U.S. laboratory that has a CLIA certification or its equivalent.
  • All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization).
  • If participating in sexual activity that could lead to pregnancy, the participant (men and women) with HCV genotype 1a infection who will receive RBV must agree to use two reliable methods of contraception simultaneously while receiving study treatment and for 6 months after stopping study treatment and participants (men and women) with HCV genotype 1b infection who will not receive RBV must agree to use two reliable methods of contraception simultaneously while receiving study treatment and for 30 days after stopping study treatment. A combination of TWO of the following contraceptives MUST be used appropriately:

    • Condoms (male or female) with or without a spermicidal agent
    • Diaphragm or cervical cap with spermicide
    • Intrauterine device (IUD)
    • Hormone-based contraceptives (only female partners of male study participants) NOTE: Hormone-based contraceptives are NOT considered an acceptable form of contraception for female study participants.
  • Participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives. More information on the criterion can be found in the protocol.
  • Ability and willingness of the participant to provide written informed consent

Step 1 Exclusion Criteria:

  • Breastfeeding
  • Pregnant sexual partner for male participants with HCV genotype 1a infection who will receive RBV. This criterion does not apply to male participants with HCV genotype 1b infection who will not receive RBV.
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
  • Acute or serious illness requiring systemic treatment and/or hospitalization within 42 days prior to study entry
  • Active hepatitis B infection (positive hepatitis B surface antigen [HBsAg]) within 42 days prior to study entry
  • History of decompensated liver disease (including but not limited to encephalopathy, variceal bleeding, or ascites) prior to study entry
  • Any cause of liver disease other than chronic HCV infection, including but not limited to the following: hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease, autoimmune hepatitis, alcoholic liver disease, or drug-related liver disease. More information on this criterion can be found in the protocol.
  • Uncontrolled or active depression or other psychiatric disorder within 24 weeks prior to study entry that in the opinion of the site investigator might preclude adherence to study requirements
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Serious illness including uncontrolled seizure disorders, active coronary artery disease within 24 weeks prior to study entry, or other chronic medical conditions that in the opinion of the site investigator might preclude completion of the protocol
  • Presence of active or acute AIDS-defining opportunistic infections within 12 weeks prior to study entry. See the protocol for more information.
  • Active or history of malignancy within 5 years prior to study entry other than basal cell carcinoma of the skin and/or cutaneous Kaposi's sarcoma (KS) and/or cervical or anal dysplasia or carcinoma in situ
  • Clinically significant abnormal EKG, or EKG with QT interval corrected for heart rate (QTc) using Fridericia's correction formula (QTcF) greater than 450 msec within 42 days of study entry. For Fridericia's correction refer to the calculator located on the Frontier Science & Technology Research Foundation, Inc. (FSTRF) website at www.fstrf.org.
  • Use of colony stimulating factors, such as granulocyte colony stimulating factor (GCSF) or erythropoietin within 42 days of study entry
  • Infection with any HCV genotype other than genotype 1, or mixed genotype infection any time prior to study entry
  • History of major organ transplantation with an existing functional graft any time prior to study entry
  • History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency to hemolysis any time prior to study entry
  • Anticoagulants such as Coumadin (Warfarin), Dicumarol, Plavix (Clopidrogel), low-molecular weight Heparin, Lovenox (Enoxaparin), or Dabigatran (Pradaxa), aspirin, and Non-steroidal Anti-Inflammatory Drugs (NSAIDs) within 2 weeks prior to entry.

Step 2 Inclusion Criteria:

  • Completion or premature discontinuation (including HCV VF) of Step 1 study treatment (i.e., HCV) regimen. See the protocol for more information.

Step 2 Exclusion Criteria:

  • Premature study discontinuation. See the protocol for more information.
  Contacts and Locations
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): NCT02194998


  Show 33 Study Locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Mark S. Sulkowski, MD Johns Hopkins University
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02194998     History of Changes
Other Study ID Numbers: A5329
11935 ( Registry Identifier: DAIDS ES Registry Number )
First Submitted: July 17, 2014
First Posted: July 21, 2014
Last Update Posted: October 3, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Infection
Communicable Diseases
Hepatitis C
HIV Infections
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Interferons
Ribavirin
Ritonavir
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents