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Trial record 1 of 1 for:    a5327
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Sofosbuvir-Containing Regimens Without Interferon For Treatment of Acute Hepatitis C Virus (HCV) Infection (SWIFT-C)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02128217
First Posted: May 1, 2014
Last Update Posted: October 23, 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. Read our disclaimer for details.
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
  Purpose

People who are recently infected with HCV have a great chance of being cured of the infection when they are treated with a combination of two drugs within the first 6 months of being infected. This study is being done to see if a combination of two new drugs in one pill can replace the old drugs to provide a safer, more effective, and better tolerated treatment for new HCV infection. The names of the new drugs are ledipasvir (LDV) and sofosbuvir (SOF), and they will replace pegylated-interferon alfa (PEG-IFN, a drug given as a weekly injection under the skin). The fixed-dose combination of LDV and SOF (LDV/SOF) has been approved by the Food and Drug Administration (FDA).

This study started with participants in Group 1 receiving SOF in combination with RBV, a drug also approved by the FDA, for 12 weeks. There were a total of 17 participants in Group 1 and all completed treatment. All participants were monitored for safety and viral response while on treatment. After completing treatment, all participants were evaluated for a treatment response after the end of treatment.

If the treatment response in Group 1 was high enough, the study design allowed for the possibility to decrease the length of therapy for Group 2 to 8 weeks, using the same treatment. However, this did not occur. Combined with the fact that a new and more effective treatment for chronic HCV has been approved since the study started, Group 2 will now receive 8 weeks of LDV/SOF instead of 12 or 8 weeks of SOF with RBV.


Condition Intervention Phase
HIV-1 Infection Hepatitis Drug: Ribavirin Drug: Sofosbuvir Drug: Ledipasvir/Sofosbuvir Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sofosbuvir-Containing Regimens Without Interferon For Treatment of Acute HCV in HIV-1 Infected Individuals (SWIFT-C)

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • SVR12 defined as HCV RNA undetectable (<LLOQ TND) of the assay at 12 weeks after date of last dose of study treatment. [ Time Frame: At 12 weeks after date of last dose of study treatment ]
    The 12 week measurement will be the measurement obtained closest to 84 days (i.e. 12*7 days), within the window 79 to 112 days inclusive. If a participant has no HCV RNA measurement within this window, then the participant will be considered as having detectable HCV RNA at 12 weeks unless the preceding and subsequent HCV RNA measurements are both undetectable (<LLOQ TND).

  • Occurrence of a Grade ≥ 2 adverse event (AE: diagnosis, sign, symptom or laboratory abnormality), Serious AE according to ICH criteria, or treatment-limiting AE (ie, an AE reported as the reason for permanent discontinuation of study treatment) [ Time Frame: From initiation of study treatment to 28 days after last dose of study treatment ]
    Any event occurring after initiation of study treatment through to 28 days after date of last dose of study treatment will be included (except that an event that is ongoing at the same grade from before start of study treatment will be excluded).


Secondary Outcome Measures:
  • HCV RNA undetectable during study treatment [ Time Frame: 1, 2, 4, 8 and, for the 12-week regimen, 12 weeks after starting study treatment ]
    HCV RNA undetectable is defined as an HCV RNA measurement less than the assay lower limit of quantification, target not detected. If there is no measurement at a scheduled time, then the participant will be considered as having detectable HCV RNA at that time, unless both the preceding and succeeding measurements are undetectable.

  • HCV RNA undetectable after end of study treatment [ Time Frame: 2, 4, 8 and 24 weeks after last dose of study treatment ]
    HCV RNA undetectable is defined as an HCV RNA measurement less than the assay lower limit of quantification, target not detected. If there is no measurement at a scheduled time, then the participant will be considered as having detectable HCV RNA at that time, unless both the preceding and succeeding measurements are undetectable. This outcome measure is generally referred to as SVR2, SVR4, SVR8 and SVR where SVR means sustained virologic response.

  • HCV virologic relapse [ Time Frame: From end of study treatment through to 24 weeks after end of study treatment ]
    HCV RNA undetectable at end-of-treatment but HCV RNA quantifiable during follow-up with subsequent confirmation as quantifiable

  • Development of SOF or LDV-associated resistance mutations [ Time Frame: Any time from start of study treatment to 24 weeks after end of study treatment ]
    The set of mutations to be considered will be defined at the time of analysis based on information from other studies available at that time.

  • Occurrence of each type of adverse event [ Time Frame: Any time from start of treatment to 24 weeks after end of treatment ]
    The adverse events to be considered are those used to define the safety primary outcome measure

  • Change in HIV-1 RNA from last measurement prior to start of study treatment [ Time Frame: 4 and 12 weeks after start of study treatment (4 and 8 weeks after for the 8-week regimen ]
    For participants on ART at study entry, these will be categorized as changes from <50 copies/mL to ≥50 copies/mL, or vice versa; for participants not on ART at study entry, quantitative change in log10 HIV-1 RNA will be considered.

  • Change in CD4+ cell count from last measurement prior to start of study treatment. [ Time Frame: 12 weeks after start of study treatment (8 weeks after for the 8-week regimen) ]
  • Self-reported adherence to SOF [ Time Frame: 1, 2, 4, 8 and, for 12-week regimen only, 12 weeks after starting study treatment ]
    whether or not a participant reports having taken all doses of SOF

  • Self-reported adherence to RBV [ Time Frame: 1, 2, 4, 8 and, for 12-week regimen only, 12 weeks after starting study treatment ]
    whether or not a participant reports having taken all doses of RBV

  • Adherence as measured by SOF pill count [ Time Frame: 1, 2, 4, 8 and, for 12-week regimen only, 12 weeks after starting study treatment ]
    Proportion of expected SOF doses taken

  • Adherence as measured by RBV pill count [ Time Frame: 1, 2, 4, 8 and, for 12-week regimen only, 12 weeks after starting study treatment ]
    Proportion of expected RBV doses taken

  • Self-reported adherence to LDV/SOF [ Time Frame: 1, 2, 4, and 8, for 8-week regimen only, 8 weeks after starting study treatment ]
    whether or not a participant reports having taken all doses of LDV/SOF

  • Adherence as measured by LDV/SOF pill count [ Time Frame: 1, 2, 4, and 8, for 8-week regimen only, 8 weeks after starting study treatment ]
    Proportion of expected LDV/SOF doses taken


Enrollment: 44
Study Start Date: April 2014
Study Completion Date: May 9, 2017
Primary Completion Date: February 28, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: SOF+weight-based RBV for 12 wks
Follow-up will occur 24 weeks after the end of treatment.
Drug: Ribavirin
Participants will receive weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV will be based on subject's weight at entry. Changes in weight after entry do not require a change in dose. Doses will only be changed for toxicity management.
Other Name: RBV
Drug: Sofosbuvir
Participants will receive one 400 mg tablet of sofosbuvir orally every morning with food.
Other Name: SOF
Experimental: Cohort 2: LDV/SOF for 8 wks
Follow-up will occur 24 weeks after the end of treatment.
Drug: Ledipasvir/Sofosbuvir
Participants will receive one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.
Other Name: LDV/SOF

  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 and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

A5327 Eligibility Criteria (Cohort 1 and Cohort 2)

Step 1 inclusion criteria for both cohorts (Cohort 1 and Cohort 2)

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV 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 and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load. [NOTE: The term "licensed" refers to a FDA-approved kit, which is required for all IND studies.] WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
  • A documented confirmation of acute HCV infection within 6 months prior to A5327 entry or HCV reinfection as described below:

    1. Acute HCV infection will be defined as meeting one of the following criteria and exclusion of other causes of acute hepatitis:

      • New (<24 weeks prior to initial A5327 entry) ALT elevation to ≥5X upper limit of normal (ULN) OR >250 U/L in patients with documented normal ALT in the preceding 12 months or ≥10X ULN OR >500 U/L in patients with abnormal or no measured ALT baseline in the preceding 12 months with detectable HCV RNA excluding those with any prior positive anti-HCV. OR
      • Detectable HCV RNA with prior negative anti-HCV Ab or undetectable HCV RNA within the preceding 6 months.
    2. Acute HCV reinfection will be defined by documentation of clearance of prior infection (as evidenced by positive anti-HCV Ab) either spontaneously or after treatment with two negative HCV RNA a minimum of 6 months apart AND meeting one of the following criteria in addition to exclusion of other causes of acute hepatitis:

      • New (<24 weeks prior to initial A5327 entry) ALT elevation to ≥5X ULN OR >250 U/L in patients with documented normal ALT in the preceding 12 months or ≥10X ULN OR >500 U/L in patients with abnormal or no measured ALT baseline in the preceding 12 months with detectable HCV RNA. OR
      • Positive HCV RNA with prior negative HCV RNA within the preceding 6 months.
  • HCV RNA confirmed to be detectable >12 weeks after first laboratory evidence of acute HCV and still within the <24 week from first laboratory evidence of acute HCV infection window. First laboratory evidence of infection is defined as date of first elevated liver enzymes or date of first serologic evidence of HCV seroconversion and/or viremia (whichever occurs first). [NOTE: If the screening visit occurs less than 12 weeks from the first laboratory evidence of infection, then the participant will require a pre-entry study visit to confirm detectable HCV RNA at least 12 weeks from the first laboratory evidence of infection have passed. It is optimal for this pre-entry visit to occur as close as possible to 12 weeks from first laboratory evidence to ensure timely treatment. Potential participants who enter screening but who have an undetectable HCV RNA (<LLOQ TND) at the pre-entry visit (when required) will have exhibited evidence of possible spontaneous clearance and will not meet the entry criteria.]
  • Body mass index (BMI) ≥ 18 kg/m2
  • Screening electrocardiogram (ECG) without clinically significant abnormalities as determined by the investigator.
  • Willing and able to provide written informed consent.
  • Men and women age ≥ 18 years.
  • All participants must agree not to participate in a conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization). [NOTE: Female candidates who are pregnant or breastfeeding are not eligible. A male candidate who has a pregnant female partner is not eligible for the study.]
  • When participating in sexual activity that could lead to pregnancy, all participants must agree to use at least two reliable forms of contraceptive simultaneously while receiving protocol-specified medications, and for 6 months after stopping the medications. Such methods include:

    • Condoms (male or female) with or without a spermicidal agent
    • Diaphragm or cervical cap with spermicide
    • Intrauterine device (IUD)
    • Tubal ligation
    • Hormone-based contraceptive (except those containing drospirenone)

[NOTE: Providers and participants should be advised that not all contraceptive choices listed above can prevent HIV transmission and that some may actually increase the risk of HIV acquisition. Study participants who are sexually active with HIV-1 negative or unknown HIV-1 serostatus partners should be advised that they need to consider effective strategies for reducing the risk of HIV transmission, as well as meeting the requirement for effective contraception during their participation in the study. Study participants should discuss contraceptive choices and HIV risk reduction methods with their health care provider.]

  • Participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy or men who have documented azoospermia or undergone vasectomy) are eligible without requiring the use of contraceptives. Acceptable documentation of sterilization and menopause is specified below.

    • Written or oral documentation communicated by clinician or clinician's staff of one of the following:
    • Physician report/letter
    • Operative report or other source documentation in the patient record (a laboratory report of azoospermia is required to document successful vasectomy)
    • Discharge summary
    • Follicle stimulating hormone-release factor (FSH) measurement elevated into the menopausal range as established by the reporting laboratory.
  • Intention to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.

Step 1 inclusion criteria for Cohort 1 only

  • HIV-1 ARV therapy should fall into one of the following criteria:

    1. ARV untreated, for example due to (1) lack of indication per provider (CD4 T-cell count >500 cells/mm3) or (2) decision by provider and participant to defer ARV therapy during the study drug dosing period (8 or 12 weeks), or (3) elite controller (CD4+ >200 cells/mm3). OR
    2. On a stable, protocol-approved (ddI, d4T, ZDV excluded), ARV regimen for >8 weeks prior to screening with a CD4 T-cell count >200 cells/mm3 and a documented plasma HIV-1 RNA level <50 copies/mL or <LLOQ of local assay if LLOQ is >50 copies/mL by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent ≥ 8 weeks preceding the A5327 screening visit. HIV-1 RNA levels should be within 1 year of the screening visit. Screening HIV-1 RNA must be < 50 copies/mL as measured by any local laboratory using an FDA-approved assay.
  • Candidates must have the following laboratory parameters within 10-42 days prior to study entry:

    1. Hemoglobin ≥ 12 g/dL for male, ≥11 g/dL for female participants
    2. International normalized ratio (INR) ≤1.5 x ULN unless participant has known hemophilia or is stable on an anticoagulant regimen affecting INR
    3. Albumin ≥ 3 g/dL
    4. Creatinine clearance (CrCl) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation (refer to section 6.3.5 for calculator utility link)
  • Female participants of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must have a negative serum pregnancy test with a sensitivity of at least 25 mIU/mL performed during screening, within 48 hours prior to study entry.

Step 1 inclusion criteria for Cohort 2 only

  • HCV genotype 1a, 1b, or 4 infection with source documentation from a CLIA-approved laboratory (or its equivalent). [NOTE: Those with mixed 1a/b genotype will be classified as 1a.]
  • HIV-1 ARV therapy should fall into one of the following criteria:

    1. ARV untreated, for example due to (1) lack of indication per provider (CD4 T-cell count >500 cells/mm3) or (2) decision by provider and participant to defer ARV therapy during the study drug dosing period (8 or 12 weeks), or (3) elite controller (CD4+ >200 cells/mm3). OR
    2. On a stable, protocol-approved ARV regimen (the following ARVs are not allowed: ddI, d4T, and TPV/r) for >8 weeks prior to screening with a CD4 T-cell count >200 cells/mm3 and a documented plasma HIV-1 RNA level <50 copies/mL or <LLOQ of local assay if LLOQ is >50 copies/mL by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent ≥ 8 weeks preceding the A5327 screening visit. HIV-1 RNA levels should be within 1 year of the screening visit. Screening HIV-1 RNA must be <50 copies/mL as measured by any local laboratory using an FDA-approved assay.
  • Candidates must have the following laboratory parameters within 10-42 days prior to study entry:

    1. Hemoglobin ≥9 g/dL for male and female participants
    2. International normalized ratio (INR) ≤1.5 x ULN unless participant has known hemophilia or is stable on an anticoagulant regimen affecting INR
    3. Albumin ≥3 g/dL
    4. Creatinine clearance (CrCl) ≥60 mL/min, as calculated by the Cockcroft-Gault equation (refer to section 6.3.5 for calculator utility link)
  • Female participants of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must have a negative serum or urine pregnancy test within 48 hours prior to study entry by any laboratory or clinic that has a CLIA certificate or its equivalent, or is using a point-of-care (POC)/CLIA-waived test. The serum, urine or POC pregnancy test must have a sensitivity of at least 25 mIU/mL.

Step 1 exclusion criteria for both cohorts (Cohort 1 and Cohort 2)

  • Received investigational drug or device within 60 days prior to study entry.
  • Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, primary sclerosing cholangitis).
  • Presence of active or acute AIDS-defining opportunistic infections within 30 days prior to study entry. [NOTE: A list of AIDS-defining opportunistic infections as defined by the CDC, can be found in Appendix B of the following document: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm]
  • Active, serious infection (other than HIV-1 or HCV) requiring parenteral antibiotics, antivirals, or antifungals within 30 days prior to study entry.
  • Infection with hepatitis B virus (HBV) defined as HBsAg positive.
  • Evidence of acute hepatitis A infection defined as HAV IGM positive.
  • Chronic use of systemically administered immunosuppressive agents (eg, prednisone equivalent > 10 mg/day).
  • History of solid organ transplantation.
  • Current or prior history of clinical hepatic decompensation (eg, ascites, encephalopathy or variceal hemorrhage).
  • History of a gastrointestinal disorder (or post operative condition) that could interfere with the absorption of the study drug.
  • History of significant or symptomatic pulmonary disease, cardiac disease, or porphyria.
  • History of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
  • History of clinically significant illness or any other major medical disorder that may interfere with participant treatment, assessment, or compliance with study requirements, which may include active drug or alcohol use or dependence.
  • Use of any prohibited concomitant medications within 30 days prior to study entry.
  • Acute HIV infection defined as the phase immediately following infection during which anti-HIV antibodies are undetectable. [NOTE: Participants with early infection, defined as within the first 6 months of infection and with a positive HIV antibody, should be discussed with the A5327 protocol core team. These participants may be considered for inclusion in the study on a case by case basis with the specific documented approval of the protocol chairs.]

Step 1 exclusion criteria for Cohort 1 only

  • Prior exposure to a direct-acting antiviral (DAA) targeting the HCV NS5B polymerase. [NOTE: DAAs include but are not limited to: mericitabine, ABT-333, ABT-072, BI-207127, BMS-791325, VX-222, tegobuvir, IDX719, setrobuvir, GS-9669, VX-135.]
  • History of clinically significant hemoglobinopathy (eg, sickle cell disease, thalassemia).
  • Known hypersensitivity to RBV, SOF, its metabolites, or formulation excipients or any other contraindication to the use of RBV or SOF.
  • Currently receiving ZDV, ddI, or d4T.

Step 1 Exclusion criteria for Cohort 2 only

  • Any preceding attempt at HCV treatment during this acute HCV infection episode, ie, 24 weeks prior to entry.
  • Known hypersensitivity to SOF or LDV, the metabolites, or formulation excipients or any other contraindication to the use of SOF or LDV.
  • Currently receiving TPV/r, ddI, d4T or amiodarone.
  • Pregnancy or Breastfeeding.
  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): NCT02128217


Locations
United States, California
701 University of California, San Diego AntiViral Research Center CRS
San Diego, California, United States, 92103
801 University of California, San Francisco HIV/AIDS CRS
San Francisco, California, United States, 94110
United States, Colorado
6101 University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Georgia
5802 The Ponce de Leon Center CRS
Atlanta, Georgia, United States, 30308
United States, Illinois
2701 Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Maryland
201 Johns Hopkins University CRS
Baltimore, Maryland, United States, 21205
United States, Massachusetts
101 Massachusetts General Hospital (MGH) CRS
Boston, Massachusetts, United States, 02114
107 Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, United States, 02115
United States, Missouri
2101 Washington University Therapeutics (WT) CRS
Saint Louis, Missouri, United States, 63110
United States, New York
7804 Weill Cornell Chelsea CRS
New York, New York, United States, 10010
7803 Weill Cornell Upton CRS
New York, New York, United States, 10065
United States, North Carolina
3201 Chapel Hill CRS
Chapel Hill, North Carolina, United States, 27516
United States, Ohio
2401 Cincinnati CRS
Cincinnati, Ohio, United States, 45267-0405
United States, Pennsylvania
6201 Penn Therapeutics CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
2951 The Miriam Hospital (TMH) ACTG CRS
Providence, Rhode Island, United States, 02906
United States, Texas
31443 Trinity Health and Wellness Center CRS
Dallas, Texas, United States, 75208
31473 Houston AIDS Research Team (HART) CRS
Houston, Texas, United States, 77030
Puerto Rico
5401 Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, Puerto Rico, 00931
Sponsors and Collaborators
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Raymond T Chung, M.D. Massachusetts General Hospital
Study Chair: Susanna Naggie, M.D. Duke University
  More Information

Additional Information:
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT02128217     History of Changes
Other Study ID Numbers: ACTG A5327
UM1AI068636 ( U.S. NIH Grant/Contract )
First Submitted: April 29, 2014
First Posted: May 1, 2014
Last Update Posted: October 23, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Infection
Hepatitis
Liver Diseases
Digestive System Diseases
Interferons
Ribavirin
Sofosbuvir
Ledipasvir
Ledipasvir, sofosbuvir drug combination
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action