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

NCT ID: NCT02475655

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-16
• Study Completion Date: 2018-04-04

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).

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

10 mg orally twice daily for 5 weeks

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Ruxolitinib

10 mg orally twice daily for 5 weeks

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vincent Marconi, MD

Role: STUDY_CHAIR

Emory University

Jeffrey Lennox, MD

Role: STUDY_CHAIR

Emory University

Locations

Alabama CRS

Birmingham, Alabama, United States

UCLA CARE Center CRS

Los Angeles, California, United States

UCSD Antiviral Research Center CRS

San Diego, California, United States

Ucsf Hiv/Aids Crs

San Francisco, California, United States

Northwestern University CRS

Chicago, Illinois, United States

Washington University Therapeutics (WT) CRS

St Louis, Missouri, United States

Weill Cornell Chelsea CRS

New York, New York, United States

Weill Cornell Uptown CRS

New York, New York, United States

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, United States

Cincinnati Clinical Research Site

Cincinnati, Ohio, United States

Case Clinical Research Site

Cleveland, Ohio, United States

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, United States

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, United States

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, United States

Countries

United States

References

Marconi VC, Moser C, Gavegnano C, Deeks SG, Lederman MM, Overton ET, Tsibris A, Hunt PW, Kantor A, Sekaly RP, Tressler R, Flexner C, Hurwitz SJ, Moisi D, Clagett B, Hardin WR, Del Rio C, Schinazi RF, Lennox JJ. Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults With Human Immunodeficiency Virus. Clin Infect Dis. 2022 Jan 7;74(1):95-104. doi: 10.1093/cid/ciab212.

Reference Type: DERIVED

PMID: 33693561 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://rsc.niaid.nih.gov/sites/default/files/daids-ae-grading-table-v2-nov2014.pdf

DAIDS AE Grading Table, Version 2.0, November 2014

https://rsc.niaid.nih.gov/sites/default/files/manual-exped-aes-v2_0.pdf

Version 2.0 of the DAIDS EAE Manual

Other Identifiers

11977

Identifier Type: REGISTRY

Identifier Source: secondary_id

A5336

Identifier Type: -

Identifier Source: org_study_id