Evaluating the Safety and Tolerability of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Randomized, Pilot Study of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults|
- Occurrence of any one of the following safety milestones (from entry to Week 5) [ Time Frame: Measured through Week 5 ]
- For participants with entry CD4+ T cell count less than 700 cells/mm^3, confirmed CD4+ decline greater than 33% of baseline and to less than 350 cells/mm^3.
- For participants with entry CD4+ T cell count greater than or equal to 700 cells/mm^3, a confirmed CD4+ T cell decline greater than 50% of baseline.
- Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption in ART.
- New or recurrent Centers for Disease Control and Prevention (CDC) category C AIDS-indicator condition.
- HIV-1 associated infection including herpes zoster.
- Lymphoproliferative malignancies.
- Discontinuation of ruxolitinib due to thrombocytopenia.
- Grade 4 or recurrence of Grade 3 anemia/neutropenia.
- Any Grade 4 or recurrence of Grade 3 toxicity related to study drug.
- New diagnosis of pneumonia, sepsis, or bacteremia.
- Occurrence of premature discontinuation of study treatment [ Time Frame: Measured through Week 5 ]
- Participant-specific change in the level of plasma interleukin 6 (IL-6) [ Time Frame: Measured through Week 5 ]Using geometric means of two enzyme-linked immunosorbent assay (ELISA) measurements at pre-entry and entry, and Weeks 4 and 5
- Proportion of participants who experienced any one of the primary safety milestones during total follow-up [ Time Frame: Measured through Week 12 ]
- Change in the level of plasma IL-6 from baseline to Weeks 4, 5, 10, and 12 [ Time Frame: Measured through Week 12 ]
- Changes in soluble markers of immune activation and inflammation in the peripheral blood from baseline to Weeks 4, 5, and 12 [ Time Frame: Measured through Week 12 ]sCD14, tumor necrosis factor alpha (TNF-α), IL-1α, IL-1-β, macrophage colony stimulating factor (m-CSF), and neopterin
- Changes in cellular markers of immune activation and inflammation in the peripheral blood from baseline to Weeks 5 and 12 [ Time Frame: Measured through Week 12 ]HLA-DR, CD38, CD69, and CD14+/CD16+ monocyte levels
- Changes in plasma HIV-1 RNA and CD4+ T cell counts from baseline to Weeks 2, 5, and 12 [ Time Frame: Measured through Week 12 ]
- Changes in HIV-1 reservoir from baseline to Weeks 5 and 12 [ Time Frame: Measured through Week 12 ]HIV-1 RNA by single-copy assay (SCA), cellular HIV-1 total RNA and DNA, 2 long terminal repeat sequences (LTRs), integrated DNA
- Level of human herpes viruses (HHV) shedding (CMV, EBV, HHV 6, 7, 8) at pre-entry, entry, and Weeks 1, 2, 4, 5, 10, and 12 [ Time Frame: Measured through Week 12 ]
- Hematology profile [ Time Frame: Measured through Week 12 ]Hemoglobin, hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), white blood cells (WBC), differential WBC, absolute neutrophil count (ANC), platelets
- Liver function profile [ Time Frame: Measured through Week 12 ]AST (SGOT), ALT (SGPT), alkaline phosphatase, indirect bilirubin, direct bilirubin, and total bilirubin
- Blood chemistries profile [ Time Frame: Measured through Week 12 ]Electrolytes (sodium, potassium, chloride, bicarbonate), glucose, creatinine, blood urea nitrogen (BUN), and CrCl as estimated by the Cockcroft-Gault equation
- Fasting lipid panel profile [ Time Frame: Measured through Week 12 ]Cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL). If the LDL cannot be calculated due to elevated triglyceride levels, a direct LDL should be measured.
|Study Start Date:||February 2016|
|Estimated Primary Completion Date:||February 2018 (Final data collection date for primary outcome measure)|
Experimental: Arm A: Ruxolitinib
Participants will receive ruxolitinib twice a day for 5 weeks. Participants must remain on ART regimen (not provided by the study) for the duration of the study.
10 mg orally twice daily for 5 weeks
No Intervention: Arm B: No Study Treatment
Participants will not receive any study treatment. Participants should be encouraged to remain on ART regimen for the duration of the 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 is to evaluate the safety and tolerability of ruxolitinib in HIV-infected adults who are on ART and who are virologically suppressed. Researchers will evaluate the effect ruxolitinib has on inflammation and immune activation.
This study will enroll HIV-infected adults who are on select ART regimens and who have viral suppression. ART will not be provided by the study; participants will continue to receive ART from their own health care providers. Participants will be randomly assigned to receive either ruxolitinib (Arm A) or no study treatment (Arm B). Participants in Arm A will receive ruxolitinib twice a day for 5 weeks. All participants will attend study visits at entry (Day 0) and Weeks 1, 2, 4, 5, 10, and 12. These visits will include 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 will take part in pharmacokinetic (PK) sampling, which will involve having blood drawn several times over 6 to 8 hours.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02475655
|United States, Alabama|
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|Rochester, New York, United States, 14642|
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|Study Chair:||Vincent Marconi, MD||Emory University|
|Study Chair:||Jeffrey Lennox, MD||Emory University|