Evaluating the Safety and Tolerability of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Ruxolitinib
Intervention description: 10 mg orally twice daily for 5 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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).
    

Eligibility 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.