Study Stopped
The study closed to accrual before the planned accrual goal was attained due to the availability of newer directly-acting antiviral (DAA) treatments for HCV.
Evaluating the Safety and Effectiveness of Interferon-Free Treatment of Hepatitis C Virus Infection in HIV-Coinfected Adults on Antiretroviral Therapy
C_ASCENT
Interferon-Free Therapy for Chronic Hepatitis C Virus Genotype 1 Infection in Participants With HIV-1 Coinfection Receiving Concurrent Antiretroviral Therapy (C_ASCENT)
2 other identifiers
interventional
46
2 countries
16
Brief 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 was to evaluate the safety, tolerability, and effectiveness of IFN-free HCV treatment in HIV/HCV coinfected adults who were taking antiretroviral (ARV) therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 hiv-infections
Started Sep 2015
Typical duration for phase_2 hiv-infections
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 17, 2014
CompletedFirst Posted
Study publicly available on registry
July 21, 2014
CompletedStudy Start
First participant enrolled
September 16, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 17, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
November 13, 2018
CompletedResults Posted
Study results publicly available
June 4, 2019
CompletedNovember 4, 2021
May 1, 2019
2.7 years
July 17, 2014
May 16, 2019
November 2, 2021
Conditions
Outcome Measures
Primary Outcomes (6)
Percentage of Participants With Sustained Virologic Response at 12 Weeks After HCV Treatment Discontinuation (SVR12)
SVR12 was defined as HCV RNA less than the assay LLOQ (\<15 IU/mL) at 12 weeks post HCV treatment discontinuation. A two-sided 90% confidence interval was calculated for the percentage of participants with SVR12 response using Clopper-Pearson method. For those whose HCV early responses prior to SVR12 evaluation met the guidelines for HCV Virologic Failure (VF), their SVR12 outcome was defined as non-response. Those missing a HCV RNA result from the week 12 post HCV treatment discontinuation visit (and missing all subsequent evaluations) were considered non-responders. However, if HCV RNA evaluations subsequent to week 12 post treatment discontinuation were non-missing, then the first HCV RNA subsequent to week 12 post treatment discontinuation was instead used to define the primary outcome.
At 12 weeks after last dose of HCV study treatment. The duration for study treatment for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively.
Number of Participants With an Occurrence of Serious Adverse Events (SAEs) as Defined by International Conference on Harmonisation (ICH) Criteria
Participants who experienced at least one observed SAEs as defined by ICH after initiating HCV study treatment through 30 days post date of last dose of HCV study treatment.
From treatment initiation to 30 days post date of last dose of HCV study treatment (whether planned or premature discontinuation). The duration for HCV study treatment for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively.
Number of Participants Who Prematurely Discontinued HCV Study Treatment for Any Reason Other Than HCV Virologic Failure (VF)
HCV VF was defined as follows: confirmed increase from nadir in HCV RNA (defined as two consecutive HCV RNA measurements of \>1 log10 IU/mL above nadir) at any time point; failure to achieve HCV RNA \<LLOQ (\<15 IU/mL) by week 6; confirmed HCV RNA ≥LLOQ (defined as two consecutive HCV RNA measurements ≥LLOQ (≥15 IU/mL)) at any point after HCV RNA \<LLOQ during HCV treatment
From treatment initiation to either 24 weeks (for Cohort A and C) or 12 weeks (for Cohort B and D). The duration for HCV study treatment for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively.
Number of Participants With an Occurrence of Signs/Symptoms Grade 3 or Higher
Participants with signs/symptoms of grade 3 or higher post treatment initiation. Participants with grade 3 sign/symptom prior to treatment initiation must have had one grade higher than pre-treatment to meet this outcome. Severity grading was based on DAIDS AE Grading Table, Version 1.0.
From treatment initiation to 30 days post date of last dose of HCV study treatment (whether planned or premature discontinuation). The duration for HCV study treatment for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively.
Number of Participants With an Occurrence of Diagnoses Leading to Premature HCV Study Treatment or HIV-1 Antiretroviral (ARV) Discontinuation.
Participants who had diagnoses leading to premature HCV study treatment or HIV-1 ARV discontinuation post treatment initiation.
From treatment initiation to end of study follow-up at 48 weeks.The duration for HCV study treatment for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively. The duration for ARV treatment for all cohorts was 48 weeks.
Number of Participants With an Occurrence of Laboratory Abnormality Grade 3 or Higher.
Participants with an observed laboratory abnormalities grade 3 or higher post treatment initiation. If entry (pre-treatment) lab result was grade 3, then a grade 4 result was required to meet this outcome. Severity grading was based on DAIDS AE Grading Table, Version 1.0.
From treatment initiation to 30 days post date of last dose of HCV study treatment (whether planned or premature discontinuation). The duration for HCV study treatment for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively.
Secondary Outcomes (8)
Number of Participants Who Experienced HIV-1 Virologic Failure (VF)
From treatment initiation to 4 weeks after last dose of HCV study treatment. HIV-1 RNA was measured at weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, and 28. The durations for HCV study treatment for Cohorts A/C and Cohorts B/D were 24 and 12 weeks, respectively.
Number of Participants With Selected HIV-1 Resistance Mutations Among Participants Who Experience HIV-1 Virologic Failure (VF)
At confirmation of HIV-1 virologic failure.
Levels of Soluble CD14 (sCD14)
At baseline, end of HCV treatment (EOT), and 12 weeks post EOT. The EOT for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively.
Change in Soluble CD14 (sCD14)
At baseline, end of HCV treatment (EOT), and 12 weeks post EOT. The EOT for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively.
Levels of IP-10 Concentration.
At baseline, end of HCV treatment (EOT), and 12 weeks post EOT. The EOT for Cohorts A and C and Cohorts B and D was 24 and 12 weeks, respectively.
- +3 more secondary outcomes
Study Arms (4)
Cohort A [INI-based ART + PTV/r/OBT + DSV +/- RBV 24 Weeks]
EXPERIMENTALParticipants took an INI-based (RAL or DTG) ART regimen for HIV-1 and received the following medications for 24 weeks: paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV) (RBV for all participants (version 1) and only for participants with HCV genotype 1a (version 2)).
Cohort B [INI-based ART + PTV/r/OBT + DSV +/- RBV 12 Weeks]
EXPERIMENTALParticipants took an INI-based (RAL or DTG) ART regimen for HIV-1 and received the following medications for 12 weeks: paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV) (RBV for all participants (version 1) and only for participants with HCV genotype 1a (version 2)).
Cohort C [PI-based ART + PTV/r/OBT + DSV +/- RBV 24 Weeks]
EXPERIMENTALParticipants took a PI-based (DRV or ATV) ART regimen for HIV-1 and received the following medications for 24 weeks: paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV) (RBV for all participants (version 1) and only for participants with HCV genotype 1a (version 2)).
Cohort D [PI-based ART + PTV/r/OBT + DSV +/- RBV 12 Weeks]
EXPERIMENTALParticipants took a PI-based (DRV or ATV) ART regimen for HIV-1 and received the following medications for 12 weeks: paritaprevir/ritonavir/ombitasvir (PTV/r/OBT), dasabuvir (DSV), and ribavirin (RBV) (RBV for all participants (version 1) and only for participants with HCV genotype 1a (version 2)).
Interventions
PTV/r/OBT: 150/100/25 mg (two 75/50/12.5 mg fixed-dose combination tablets) orally once a day
DSV: 250 mg orally twice a day
RBV: 1,000 or 1,200 mg (weight-based) dosed in two divided doses orally twice a day (all participants (version 1); only participants with HCV genotype 1a (version2))
Eligibility Criteria
You may qualify if:
- 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 was calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
- HIV-1 infection
- 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.
- On a stable, qualifying ART regimen for at least 8 weeks prior to entry.
- HIV-1 RNA less than 50 copies/mL for at least 6 months prior to study entry.
- 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) was allowed.
- HCV genotype 1a or 1b infection
- Serum HCV RNA greater than 10,000 IU/mL obtained within 42 days prior to study entry.
- 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
- +14 more criteria
You may not qualify if:
- Breastfeeding
- Pregnant sexual partner for male participants with HCV genotype 1a infection who would receive RBV. This criterion did not apply to male participants with HCV genotype 1b infection who would 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.
- 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.
- 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.
- 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.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
Alabama CRS
Birmingham, Alabama, 35294, United States
UCLA CARE Center CRS
Los Angeles, California, 90035, United States
University of Colorado Hospital CRS
Aurora, Colorado, 80045, United States
Whitman-Walker Health CRS
Washington D.C., District of Columbia, 20005, United States
Rush University CRS
Chicago, Illinois, 60612, United States
Johns Hopkins University CRS
Baltimore, Maryland, 21205, United States
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, 07103, United States
Weill Cornell Chelsea CRS
New York, New York, 10010, United States
Cincinnati Clinical Research Site
Cincinnati, Ohio, 45219, United States
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, 15213, United States
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
Providence, Rhode Island, 02906, United States
Trinity Health and Wellness Center CRS
Dallas, Texas, 75208, United States
Houston AIDS Research Team CRS
Houston, Texas, 77030, United States
University of Washington AIDS CRS
Seattle, Washington, 98104-9929, United States
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, 00935, Puerto Rico
Related Publications (1)
Anthony DD, Sulkowski MS, Smeaton LM, Damjanovska S, Shive CL, Kowal CM, Cohen DE, Bhattacharya D, Alston-Smith BL, Balagopal A, Wyles DL. Hepatitis C Virus (HCV) Direct-Acting Antiviral Therapy in Persons With Human Immunodeficiency Virus-HCV Genotype 1 Coinfection Resulting in High Rate of Sustained Virologic Response and Variable in Normalization of Soluble Markers of Immune Activation. J Infect Dis. 2020 Sep 14;222(8):1334-1344. doi: 10.1093/infdis/jiaa254.
PMID: 32406487DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- ACTG Clinicaltrials.gov Coordinator
- Organization
- ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Study Officials
- STUDY CHAIR
Mark S. Sulkowski, MD
Johns Hopkins University
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 17, 2014
First Posted
July 21, 2014
Study Start
September 16, 2015
Primary Completion
May 17, 2018
Study Completion
November 13, 2018
Last Updated
November 4, 2021
Results First Posted
June 4, 2019
Record last verified: 2019-05