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OpenTrials
Completed

NCT Number: NCT02475655

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

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).

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Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Alabama CRS, Birmingham, Alabama, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Ruxolitinib

Drug

10 mg orally twice daily for 5 weeks

Primary outcomes

  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 outcomes

  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 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.

  22. 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.

  23. 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).

  24. Fold Change in the Level of Plasma Tumor Necrosis Factor Alpha (TNF Alpha)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  25. Fold Change in the Level of Plasma Interleukin 1 Beta (IL-1 Beta)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  26. Fold Change in the Level of Plasma Interleukin 7 (IL-7)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  27. Fold Change in the Level of Interleukin 1 Alpha (IL-1 Alpha)

    Time frame: Pre-entry, Entry, Weeks 4, 5, and 12

    Laboratory testing was not performed so the data are not available.

  28. Fold Change in the Level of Interferon Gamma-induced Protein 10 (IP-10)

    Time frame: Pre-entry, Entry, Weeks 4, 5, and 12

    Laboratory testing was not performed so the data are not available.

  29. Fold Change in the Level of Macrophage Colony-stimulating Factor

    Time frame: Pre-entry, Entry, Weeks 4, 5, and 12

    Laboratory testing was not performed so the data are not available.

  30. Fold Change in the Level of Neopterin

    Time frame: Pre-entry, Entry, Weeks 4, 5, and 12

    Data not available because the testing lab reported that the values were unreliable.

  31. Fold Change in the Level of Plasma Interleukin 10 (IL-10)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  32. Fold Change in the Level of Plasma Interleukin 15 (IL-15)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  33. Fold Change in the Level of Plasma Interleukin 18 (IL-18)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  34. Fold Change in the Level of Plasma Transforming Growth Factor Beta 1 (TGF Beta-1)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  35. Fold Change in the Level of Plasma Transforming Growth Factor Beta 2 (TGF Beta-2)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  36. Fold Change in the Level of Plasma Transforming Growth Factor Beta 3 (TGF Beta-3)

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  37. Change in (CD3+CD4+) CD38+HLADR+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD4+) that express CD38+HLADR+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  38. Change in (CD3+CD8+) CD38+HLADR+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD8+) that express CD38+HLADR+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  39. Change in (CD3+CD4+) CD25hi+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD4+) that express CD25hi+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  40. Change in (CD3+CD8+) CD25+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD8+) that express CD25+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  41. Change in (CD3+CD4+) CD127+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD4+) that express CD127+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  42. Change in (CD3+CD8+) CD127+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD8+) that express CD127+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  43. Change in (CD3+CD4+) Ki67+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD4+) that express Ki67+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  44. Change in (CD3+CD8+) Ki67+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD8+) that express Ki67+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  45. Change in (CD3+CD4+) Bcl2+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD4+) that express Bcl2+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  46. Change in (CD3+CD8+) Bcl2+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD8+) that express Bcl2+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  47. Change in (CD3+CD4+) a4b7+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD4+) that express a4b7+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  48. Change in (CD3+CD8+) a4b7+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD8+) that express a4b7+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  49. Change in (CD3+CD4+) CX3CR1+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD4+) that express CX3CR1+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  50. Change in (CD3+CD8+) CX3CR1+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of parent cells (CD8+) that express CX3CR1+ cells (cellular marker of immune activation and inflammation in the peripheral blood).

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  51. Change in CD69

    Time frame: Entry, Weeks 5 and 12

    Data not available because the team decided they were no longer clinically relevant, so samples were not tested for CD69.

  52. Change in PAR-1

    Time frame: Entry, Weeks 5 and 12

    Data not available because the team decided they were no longer clinically relevant, so samples were not tested for PAR-1.

  53. Change in Classical Monocytes (CD14+CD16-)

    Time frame: Entry, Weeks 5 and 12

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  54. Change in Classical Monocytes (CD14+CD16-) Expressing CD163+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of classical monocytes (CD14+CD16-) that express CD163+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  55. Change in Classical Monocytes (CD14+CD16-) Expressing CCR2+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of classical monocytes (CD14+CD16-) that express CCR2+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  56. Change in Classical Monocytes (CD14+CD16-) Expressing CX3CR1+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of classical monocytes (CD14+CD16-) that express CX3CR1+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  57. Change in Inflammatory Monocytes (CD14+CD16+)

    Time frame: Entry, Weeks 5 and 12

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  58. Change in Inflammatory Monocytes (CD14+CD16+) Expressing CD163+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of inflammatory monocytes (CD14+CD16-) that express CD163+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  59. Change in Inflammatory Monocytes (CD14+CD16+) Expressing CCR2+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of inflammatory monocytes (CD14+CD16+) that express CCR2+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  60. Change in Inflammatory Monocytes (CD14+CD16+) Expressing CX3CR1+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of inflammatory monocytes (CD14+CD16+) that express CX3CR1+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  61. Change in Patrolling Monocytes (CD14dimCD16+)

    Time frame: Entry, Weeks 5 and 12

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  62. Change in Patrolling Monocytes (CD14dimCD16+) Expressing CD163+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CD163+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  63. Change in Patrolling Monocytes (CD14dimCD16+) Expressing CCR2+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CCR2+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  64. Change in Patrolling Monocytes (CD14dimCD16+) Expressing CX3CR1+

    Time frame: Entry, Weeks 5 and 12

    Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CX3CR1+.

    Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.

  65. Fold Change in Cellular HIV-1 DNA

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  66. Fold Change in Cellular HIV-1 Total RNA

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

  67. Percentage of Participants With Detectable CMV Shedding

    Time frame: Pre-entry, Entry, and Weeks 1, 2, 4, 5, 10, and 12

    Level of CMV shedding was summarized by study week and arm as the percentage of those above and below the assay limit of detection.

    Detectable CMV shedding was defined as CMV level > 0 copies/ml of elution. The percentage 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) was contrasted between study arms.

  68. Ruxolitinib Systemic Clearance (CL/F) From 2-compartment Pharmacokinetic (PK)

    Time frame: Week 1 and, Week 4/5; blood samples were drawn pre-dose and at 1-1.5, 2.5-4, 4-6, and 6-8 hours post-dosing

    Ruxolitinib plasma concentrations were fitted to a population 2-compartment distribution model, assuming first-order input, distribution and elimination from the plasma compartment, using nonlinear mixed-effects modeling software. We estimated parameter geometric means and proportional variabilities between subjects (IIV when feasible) and the variability in drug absorption between occasions (IOV week 1 and week 4/5), and related distribution volumes to body weight.

Other outcomes

  1. Change in 2 Long-terminal Repeat Sequences [LTRs]

    Time frame: Entry, Week 5, and Week 12

    Data not available because all values were below assay limit.

  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.

  3. Fold Change in Integrated DNA

    Time frame: Entry, Weeks 5 and 12

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

    Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.

Sponsors and collaborators

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Nih

Registry information

Official study title

A Randomized, Pilot Study of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Jun 19, 2015
Registry last updated
Nov 4, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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