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Evaluating the Safety and Tolerability of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults

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.
 
ClinicalTrials.gov Identifier: NCT02475655
Recruitment Status : Completed
First Posted : June 19, 2015
Results First Posted : April 18, 2019
Last Update Posted : April 18, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
The purpose of this study was to evaluate the safety and tolerability of ruxolitinib in HIV-positive adults who were virologically suppressed and who were on antiretroviral therapy (ART).

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Ruxolitinib Phase 2

Detailed Description:

Ruxolitinib is a medication approved by the U.S. Food and Drug Administration (FDA) to treat myelofibrosis, a disorder in which bone marrow is replaced by scar (fibrosis) tissue. Many of the cytokines affected by myelofibrosis are also affected by HIV. Because of this, ruxolitinib may also be a possible treatment for HIV. The purpose of this study was to evaluate the safety and tolerability of ruxolitinib in HIV-positive adults who were on ART and who were virologically suppressed. Researchers evaluated the effect ruxolitinib had on inflammation and immune activation.

This study enrolled HIV-positive adults who were on select ART regimens and who had viral suppression. ART was not provided by the study; participants continued to receive ART from their own health care providers. Participants were randomly assigned to receive either ruxolitinib (Arm A) or no study treatment (Arm B) in 2:1 ratio. Participants in Arm A received ruxolitinib twice a day for 5 weeks. All participants attended study visits at entry (Day 0) and Weeks 1, 2, 4, 5, 10, and 12. These visits included physical examinations, clinical assessments, blood collection, adherence assessments, oral swab collection, and pregnancy testing for female participants. At Weeks 1 and 4, participants in Arm A took part in pharmacokinetic (PK) sampling, which involved having blood drawn several times over 6 to 8 hours.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Pilot Study of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults
Actual Study Start Date : May 16, 2016
Actual Primary Completion Date : February 18, 2018
Actual Study Completion Date : April 4, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Arm A: Ruxolitinib
Participants received ruxolitinib twice a day for 5 weeks. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.
Drug: Ruxolitinib
10 mg orally twice daily for 5 weeks

No Intervention: Arm B: No Study Treatment
Participants did not receive any study treatment. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.



Primary Outcome Measures :
  1. Percentage of Participants on the Ruxolitinib Arm Who Experienced Any Safety Milestone Events While On-Treatment [ Time Frame: Entry to Week 5 ]

    Events defined as safety milestones are listed below and together makeup the composite endpoint.

    • Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3)
    • Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3)
    • Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART
    • New or recurrent CDC category C AIDS-indicator condition
    • HIV-1 associated infection including Herpes zoster
    • Lymphoproliferative malignancies
    • Grade 4 or recurrence of Grade 3 anemia/neutropenia
    • New diagnosis of pneumonia, sepsis, or bacteremia
    • Discontinuation of Ruxolitinib due to thrombocytopenia
    • Any Grade 4 or recurrence of Grade 3 toxicity related to study drug

    Percent experiencing a safety milestone will be reported.


  2. Percentage of Participants Who Experienced Any Safety Milestones On-study From Entry to Week 5 [ Time Frame: Entry to Week 5 ]

    Events defined as safety milestones are listed below and together makeup the composite endpoint.

    • Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3)
    • Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3)
    • Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART
    • New or recurrent CDC category C AIDS-indicator condition
    • HIV-1 associated infection including Herpes zoster
    • Lymphoproliferative malignancies
    • Grade 4 or recurrence of Grade 3 anemia/neutropenia
    • New diagnosis of pneumonia, sepsis, or bacteremia
    • Occurrence of Grade 2 or higher thrombocytopenia
    • Any Grade 4 or recurrence of Grade 3 toxicity

    Percent experiencing a safety milestone will be reported.


  3. Percentage of Participants Who Experienced Each Safety Milestone That Occurred On-study From Entry to Week 5 [ Time Frame: Entry to Week 5 ]

    Events defined as safety milestones are listed below.

    • Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3)
    • Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3)
    • Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART
    • New or recurrent CDC category C AIDS-indicator condition
    • HIV-1 associated infection including Herpes zoster
    • Lymphoproliferative malignancies
    • Grade 4 or recurrence of Grade 3 anemia/neutropenia
    • New diagnosis of pneumonia, sepsis, or bacteremia
    • Occurrence of Grade 2 or higher thrombocytopenia
    • Any Grade 4 or recurrence of Grade 3 toxicity

    Percent experiencing each safety milestone will be reported. Safety milestone categories are not mutually exclusive.


  4. Number of Participants With Premature Discontinuation of Study Treatment in the Ruxolitinib Arm [ Time Frame: Entry to Week 5 ]
    Number of participants with premature discontinuation of study treatment are summarized.

  5. Fold Change in the Level of Plasma Interleukin 6 (IL-6) From Baseline to Week 4/5 [ Time Frame: Pre-entry, Entry, Weeks 4 and 5 ]

    All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation.

    Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Fold change was calculated as the value at Week 4/5 divided by the value at Baseline.



Secondary Outcome Measures :
  1. Percentage of Participants on the Ruxolitinib Arm Who Experienced Any Safety Milestone Events During Total Follow-up [ Time Frame: Entry to Week 12 ]

    Events defined as safety milestones are listed below and together makeup the composite endpoint.

    • Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3)
    • Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3)
    • Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART
    • New or recurrent CDC category C AIDS-indicator condition
    • HIV-1 associated infection including Herpes zoster
    • Lymphoproliferative malignancies
    • Grade 4 or recurrence of Grade 3 anemia/neutropenia
    • New diagnosis of pneumonia, sepsis, or bacteremia
    • Discontinuation of Ruxolitinib due to thrombocytopenia
    • Any Grade 4 or recurrence of Grade 3 toxicity related to study drug

    Percent experiencing a safety milestone will be reported.


  2. Percentage of Participants Who Experienced Any Safety Milestones On-study From Entry to Week 12 [ Time Frame: Entry to Week 12 ]

    Events defined as safety milestones are listed below and together makeup the composite endpoint.

    • Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3)
    • Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3)
    • Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART
    • New or recurrent CDC category C AIDS-indicator condition
    • HIV-1 associated infection including Herpes zoster
    • Lymphoproliferative malignancies
    • Grade 4 or recurrence of Grade 3 anemia/neutropenia
    • New diagnosis of pneumonia, sepsis, or bacteremia
    • Occurrence of Grade 2 or higher thrombocytopenia
    • Any Grade 4 or recurrence of Grade 3 toxicity

    Percent experiencing a safety milestone will be reported.


  3. Percentage of Participants Who Experienced Each Safety Milestone That Occurred On-study From Entry to Week 12 [ Time Frame: Entry to Week 12 ]

    Events defined as safety milestones are listed below.

    • Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm3 (for participants with entry CD4+ T cell count < 700 cells/mm3)
    • Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm3)
    • Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART
    • New or recurrent CDC category C AIDS-indicator condition
    • HIV-1 associated infection including Herpes zoster
    • Lymphoproliferative malignancies
    • Grade 4 or recurrence of Grade 3 anemia/neutropenia
    • New diagnosis of pneumonia, sepsis, or bacteremia
    • Occurrence of Grade 2 or higher thrombocytopenia
    • Any Grade 4 or recurrence of Grade 3 toxicity

    Percent experiencing each safety milestone will be reported. Safety milestone categories are not mutually exclusive.


  4. Number of Participants Who Experienced a Protocol-defined Reportable Adverse Event at Any Post-entry Time Point. [ Time Frame: Entry to Week 12 ]

    Protocol-defined reportable adverse events include: all diagnoses regardless of grade, Grade 3 or higher sign/symptoms or laboratory values, any signs/symptoms or laboratory values that led to a change in treatment or met ICH, EAE, or SAE guidelines. See the Protocol Section References for links to the EAE manual.

    This is a subset of the events reported in the Adverse Events section.


  5. Creatinine Clearance [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]
    Creatinine clearance was calculated using the Cockcroft Gault equation. The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

  6. Change in Creatinine Clearance Values From Entry [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]

    Creatinine clearance was calculated using the Cockcroft Gault equation. The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

    Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.


  7. Creatinine [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]
    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

  8. Change in Creatinine Values From Entry [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]

    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

    Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.


  9. Absolute Neutrophil Count (ANC) [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]
    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

  10. Change in Absolute Neutrophil Count (ANC) Values From Entry [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]

    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

    Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.


  11. Hemoglobin [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]
    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

  12. Change in Hemoglobin Values From Entry [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]

    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

    Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.


  13. Platelet Count [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]
    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

  14. Change in Platelet Counts From Entry [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]

    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

    Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.


  15. Aspartate Aminotransferase (AST) (SGOT) [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]
    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

  16. Change in Aspartate Aminotransferase (AST) (SGOT) Values From Entry [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]

    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

    Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.


  17. Alanine Aminotransferase (ALT) (SGPT) [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]
    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

  18. Change in Alanine Aminotransferase (ALT) (SGPT) Values From Entry [ Time Frame: Entry, Weeks 1, 2, 4, 5, 10, and 12 ]

    The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.

    Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.


  19. Fold Change in the Level of Plasma Interleukin 6 (IL-6) [ Time Frame: Pre-entry, Entry, Weeks 4, 5, 10 and 12 ]

    All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation.

    Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Week 10/12 is defined as the geometric mean of the Week 10 and Week 12 values. Fold change was calculated as the value at Week 10/12 divided by the value at Baseline and the value at Week 4/5 divided by the value at Week 10/12.


  20. Fold Change in the Level of Soluble CD14 (sCD14) [ Time Frame: Pre-entry, Entry, Weeks 4, 5, and 12 ]

    All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation.

    Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Fold change was calculated as the value at Week 4/5 divided by the value at Baseline, the value at Week 12 divided by the value at Baseline, and the value at Week 12 divided by the value at Week 4/5.


  21. Change in Soluble Markers of Immune Activation and Inflammation in the Peripheral Blood [ Time Frame: Pre-entry, Entry, Weeks 4, 5, and 12 ]

    Soluble markers of immune activation and inflammation in the peripheral blood include: TNF-α, IL-1α, IL-1β, IL-7, IL-10, IP-10, IL-18, mCSF, and neopterin.

    Data are not available as of April, 2019 for soluble markers of immune activation and inflammation in the peripheral blood. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript (e.g. IL-6 and sCD14).


  22. Change in Cellular Markers of Immune Activation and Inflammation in the Peripheral Blood [ Time Frame: Entry, Week 5, and Week 12 ]

    Cellular markers of immune activation and inflammation in the peripheral blood include: HLA-DR, CD25, CD38, CD69, CD127, Ki67, BCL2, a4b7, CX3CR1, PAR-1 measured on CD4 and CD8 cells; monocyte subsets (classical, inflammatory, and patrolling) expressing CCR2, CX3CR1, and CD163.

    Data are not available as of February, 2019 for cellular markers of immune activation and inflammation in the peripheral blood. These data are based on assays which are to be tested in batch to minimize variability. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript (e.g. IL-6 and sCD14).


  23. Number of Participants With Plasma HIV-1 RNA Level Above the Limit of Quantification [ Time Frame: Entry, Weeks 2, 5, and 12 ]
    Participants were required to be virally suppressed, with a plasma HIV-1 RNA level below 40 copies/mL. The number of participants with plasma HIV-1 RNA level above the limit of quantification is reported at each time point.

  24. Change in CD4+ T Cell Count [ Time Frame: Pre-entry, Entry, Weeks 2, 5, and 12 ]
    Baseline is defined as the average of pre-entry and entry. Absolute change was calculated as the value at Week 2 minus the value at Baseline, the value at week 5 minus the value at baseline, the value at week 12 minus the value at baseline, and the value at week 5 minus the value at week 12.

  25. Relative Risks of HIV-1 RNA by Single Copy Assay (SCA) < 0.4 Copies/mL [ Time Frame: Entry, Weeks 5 and 12 ]
    HIV-1 RNA was measured via Single Copy Assay Using Primer in Integrase (iSCA), results were reported as below or above the assay limit of detection (LOD) (LOD = 0.4 copies/mL). GEE models for binary data were used to calculate the relative risk of having HIV-1 RNA by iSCA <0.4 copies/mL (Week 5 compared to Entry, Week 12 compared to Entry, and Week 12 compared to Week 5).

  26. Change in Cellular HIV-1 Total RNA [ Time Frame: Entry, Weeks 5 and 12 ]
    Cellular HIV-1 total RNA data are not available as of February, 2019. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript (e.g. IL-6 and sCD14).

  27. Change in Cellular HIV-1 DNA [ Time Frame: Entry, Weeks 5 and 12 ]
    Cellular HIV-1 DNA data are not available as of February, 2019 for soluble markers of immune activation and inflammation in the peripheral blood. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript (e.g. IL-6 and sCD14).

  28. Level of CMV Shedding [ Time Frame: Pre-entry, Entry, and Weeks 1, 2, 4, 5, 10, and 12 ]

    Level of CMV shedding will be summarized by study week and arm as the frequency and percentage of those above and below the assay limit of detection. The proportion of participants with detectable CMV at any on-treatment time point (ever shedding at weeks 1, 2, 4, or 5) and any post-treatment time point (ever shedding at weeks 10 or 12) will be contrasted between study arms via using a two-sided mid-p Fisher's exact test with 10% type-I error.

    CMV shedding data are not available as of February, 2019. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript (e.g. IL-6 and sCD14).


  29. Pharmacokinetics of Ruxolitinb [ Time Frame: Week 1 and Week 4 ]
    Pharmacokinetic data is not available as of February, 2019. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript (e.g. IL-6 and sCD14).


Other Outcome Measures:
  1. Change in HIV-1 Reservoir [ Time Frame: Entry, Week 5, and Week 12 ]

    HIV-1 reservoir includes: 2 long-terminal repeat sequences [LTRs], and integrated DNA.

    Data not available as of February, 2019. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript (e.g. IL-6 and sCD14).


  2. Level of HHV Shedding (EBV, HSV, HHV-6, HHV-7, and HHV-8) [ Time Frame: Pre-entry, Entry, Weeks 1, 2, 4, 5, 10, and 12 ]
    Data not available because no samples were collected to test for these measures as the team decided they were no longer clinically relevant.



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 to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection
  • CD4+ T cell count greater than 350 cells/mm^3 within 45 days prior to study entry
  • Documented virologic suppression defined as HIV-1 RNA level below the limit of quantification (eg, less than 40, less than 50, or less than 75 copies/mL, depending on the assay) using an FDA-approved assay with a quantification limit of 75 copies/mL or lower for at least 48 weeks prior to study entry
  • Screening HIV-1 RNA level below the limit of quantification
  • Tuberculosis (TB) screening within 365 days of the screening visit diagnosed by tuberculin skin test or interferon gamma release assay
  • Currently on continuous ART for at least 730 days prior to study entry, defined as continuous ART for the 730 days period, inclusive, prior to study entry with no ART interruption longer than 7 consecutive days. NOTE: The current regimen must include TDF/FTC, TAF/FTC, TDF+3TC, or ABC/3TC; plus a nonnucleoside reverse transcriptase inhibitor or integrase strand transfer inhibitor (NNRTI or INSTI, not containing cobicistat) for at least 60 days, inclusive, prior to study entry.
  • The following laboratory values obtained within 45 days prior to entry:

    • Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3
    • Hemoglobin greater than 12.0 g/dL for men and greater than 11.0 g/dL for women
    • Platelets greater than or equal to 140,000/mm^3
    • Calculated creatinine clearance (CrCl) greater than or equal to 70 mL/min (by Cockcroft Gault equation)
    • Aspartate aminotransferase (AST) (SGOT) less than or equal to 1.5x upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) (SGPT) less than or equal to 1.5x ULN
    • Alkaline phosphatase less than or equal to 1.5x ULN
  • For females of reproductive potential, a negative serum or urine pregnancy test with a sensitivity of 25 mIU/mL within 72 hours, inclusive, prior to study entry
  • 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)
  • All participants of reproductive potential, who were participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception while receiving the study drugs and for 7 weeks after stopping the medications
  • Ability and willingness of participant or legal representative to provide written informed consent and attend study visits as scheduled at a participating site

Exclusion Criteria:

  • A current or past history of progressive multifocal leukoencephalopathy
  • Breastfeeding or pregnancy
  • Use of strong inhibitors or inducers of CYP3A4 including a protease inhibitor, cobicistat or entry inhibitors as part of the current ART regimen or other concomitant therapy
  • Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Acute or serious illness or infection requiring systemic treatment and/or hospitalization within 60 days prior to entry
  • Vaccinations (other than influenza) less than or equal to 45 days prior to the study entry visit.
  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy or investigational therapy less than or equal to 60 days prior to study entry
  • Any current diagnosis or past history of a significant cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, neuropsychiatric, psychiatric, or other serious illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data or affect the participant's ability to participate in the study. Diagnoses that would lead to exclusion include, but were not limited to the following:

    • CDC category C AIDS-indicator conditions
    • NOTE A: Except HIV encephalopathy, HIV wasting, esophageal candidiasis, or pneumocystis pneumonia without dissemination.
    • NOTE B: List available: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm
    • Herpes zoster (dermatomal or non-dermatomal).
    • NOTE C: A history of prior chickenpox was not exclusionary.
    • Lymphoproliferative malignancy
    • Chronic liver disease of any etiology and any degree of severity
    • Chronic hepatitis, except for hepatitis C that has been cured (defined as a Sustained Virologic Response, which is an undetectable HCV-RNA at 12 weeks or more after completing treatment measured by a sensitive, qualitative, or quantitative HCV-RNA assay)
    • Disseminated fungal infection of any type or duration that is not limited to cutaneous or mucocutaneous surfaces
    • A medical disorder that predisposes to bleeding
  • Change in the ART regimen within 12 weeks, inclusive, prior to study entry or intended modification of ART during the study.
  • History of untreated latent tuberculosis infection (LTBI) diagnosed by tuberculin skin test or interferon gamma release assay. LTBI treatment would consist of 9 months of isoniazid or an equivalent therapy completed at least 4 weeks prior to study entry.

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): NCT02475655


Locations
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United States, Alabama
Alabama CRS
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90035
UCSD Antiviral Research Center CRS
San Diego, California, United States, 92103
Ucsf Hiv/Aids Crs
San Francisco, California, United States, 94110
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Missouri
Washington University Therapeutics (WT) CRS
Saint Louis, Missouri, United States, 63110-1010
United States, New York
Weill Cornell Chelsea CRS
New York, New York, United States, 10010
Weill Cornell Uptown CRS
New York, New York, United States, 10065
University of Rochester Adult HIV Therapeutic Strategies Network CRS
Rochester, New York, United States, 14642
United States, Ohio
Cincinnati Clinical Research Site
Cincinnati, Ohio, United States, 45219
Case Clinical Research Site
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
Providence, Rhode Island, United States, 02906
United States, Tennessee
Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, United States, 37204
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Study Chair: Vincent Marconi, MD Emory University
Study Chair: Jeffrey Lennox, MD Emory University
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Statistical Analysis Plan  [PDF] April 4, 2018
Study Protocol  [PDF] May 21, 2015

Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02475655    
Other Study ID Numbers: A5336
11977 ( Registry Identifier: DAIDS-ES )
First Posted: June 19, 2015    Key Record Dates
Results First Posted: April 18, 2019
Last Update Posted: April 18, 2019
Last Verified: March 2019
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases