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Eligibility
for people ages 18 years to 70 years
Location
at San Francisco, California and other locations
Dates
study started

Description

Summary

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.

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)

Details

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 an optional substudy. Participants in the substudy will attend two study visits at entry/Day 0 and Week 4 for 12-hour intensive pharmacokinetic (PK) sampling.

Keywords

HIV Infections Interferons Ribavirin Ritonavir

Eligibility

For people ages 18 years to 70 years

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 (genotype 1a or 1b with or without evidence of cirrhosis) or unsuccessful treatment with pegylated or standard IFN alfa with or without RBV(genotype 1b with or without evidence of cirrhosis; genotype 1a without evidence of cirrhosis only). 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 cirrhotic or non-cirrhotic prior to study entry according to specified criteria. See the protocol for more information.
  • Participants classified as cirrhotic must have no evidence of hepatocellular carcinoma (HCC) as indicated by a negative ultrasound (U/S), computed tomography (CT)scan or magnetic resonance imaging (MRI) within 6 months prior to study entry. NOTE:Participants who have a U/S with results suspicious of HCC followed by a subsequent negative CT or MRI of the liver will be eligible for the study.
  • 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
  • Child-Pugh (CP) score greater than 6 at screening (cirrhotic participants only).

NOTE: To calculate the Child-Pugh score, refer to the following website:http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality

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.

Locations

  • UCLA CARE Center CRS accepting new patients
    Los Angeles, California, 90035, USA
  • UCSD Antiviral Research Center CRS not yet accepting patients
    San Diego, California, 92103, USA
  • Harbor-UCLA CRS withdrawn
    Torrance, California, 90502, USA

Details

Status
accepting new patients
Start Date
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
ID
NCT02194998
Phase
Phase 2
Study Type
Interventional
Last Updated
March 2017
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