Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)

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: NCT01276236
Recruitment Status : Completed
First Posted : January 13, 2011
Results First Posted : March 5, 2021
Last Update Posted : March 5, 2021
Sponsor:
Collaborators:
Pfizer
ViiV Healthcare
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
The purpose of this pilot study is to determine whether Maraviroc is effective in the treatment of Kaposi's Sarcoma (KS), when it does not remit with standard antiretroviral drug therapy.

Condition or disease Intervention/treatment Phase
Kaposi's Sarcoma Drug: Maraviroc Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)
Actual Study Start Date : March 9, 2011
Actual Primary Completion Date : January 31, 2015
Actual Study Completion Date : April 30, 2015


Arm Intervention/treatment
Experimental: Treatment Arm (Maraviroc)
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Drug: Maraviroc

FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.

Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.

Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.

Other Name: Selzentry(Celsentri outside US)




Primary Outcome Measures :
  1. Number of Participants With a Decrease in Kaposi's Sarcoma (KS) Total Surface Area [ Time Frame: Up to 96 weeks ]
    To assess improvements in disease, up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions. The collective surface area of the marker lesions was evaluated over the course of the study for either an increase or decrease in the total surface area of lesions using the modified AIDS Clinical Trials Group (ACTG) Oncology Committee Staging Criteria.

  2. Percent Change in KS Total Surface Area [ Time Frame: Up to 96 weeks ]
    Up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions and the the collective surface area of the marker lesions was evaluated over the course of the study. The percent decrease or increase in the total surface area of lesions was calculated from comparing measurements at baseline and through week 96, or at the last assessment if participant withdrew from the study prior to week 96.

  3. Change in Edema Grade [ Time Frame: Up to 96 weeks ]
    The presence and extent of lower extremity edema was assessed and graded on a scale from 0 to 2 in patients with a higher grade indicating a greater level of edema using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Adverse Events (AE) Grading Table), Version 1.0. Edema grade was recorded at baseline was compared with edema grades recorded at week 96, or at last assessment if participant withdrew from study prior to week 96 and an change in grade was calculated to examine whether or not a decrease in overall grade was observed. A negative value would indicate an overall decrease in the grade of lower extremity edema, and positive value would indicate an overall increase in lower extremity edema.


Secondary Outcome Measures :
  1. Change in Kaposi's Sarcoma-associated Herpesvirus (KSHV) Viral Load [ Time Frame: Up to 96 weeks ]
    Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.

  2. Percent Change in CCR5 Levels on CD4+ T-Cells [ Time Frame: Up to 96 weeks ]
    Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD4+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD4+ T-Cells

  3. Percent Change in CCR5 Levels on CD8+ T-cells [ Time Frame: Up to 96 weeks ]
    Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD8+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD8+ T-Cells

  4. Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Positive (DR-CD38+) T-cells [ Time Frame: Up to 96 weeks ]
    Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38 positive (DR-CD38+) T-cells

  5. Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Negative (DR-CD38-) T-cells [ Time Frame: Up to 96 weeks ]
    Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38- T-cells



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
  • Active biopsy confirmed KS
  • Screening plasma HIV RNA < 75 copies/mL
  • Patients have unremitting KS. Unremitting is defined as having active biopsy confirmed KS in spite of having had sustained HIV RNA < 75 copies/mL for 24 prior months. Isolated values that are detectable but < 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable.
  • >90% adherence to therapy within the preceding 30 days, as determined by self-report.
  • Both male and female subjects are eligible. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
  • Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

  • Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.
  • Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
  • Concurrent treatment with immunomodulatory drugs or therapies, or exposure to any immunomodulatory drug or therapy in past 16 weeks.
  • Prior exposure to CCR5 inhibitors
  • Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute.
  • Elevated transaminases greater than 2.5 times the upper limit of normal.
  • Evidence of cirrhosis
  • Pregnant or breastfeeding women
  • Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.
  • Local therapy for any KS index lesion in preceding 60 days, unless lesion has clearly progressed with enlargement since the local therapy

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): NCT01276236


Locations
Layout table for location information
United States, California
San Francisco General Hospital, Clinical Trials Unit
San Francisco, California, United States, 94110
Sponsors and Collaborators
University of California, San Francisco
Pfizer
ViiV Healthcare
Investigators
Layout table for investigator information
Principal Investigator: Patrick Unemori, MD University of California, San Francisco; San Francisco General Hospital (SFGH)
Principal Investigator: Toby Maurer, MD University of California, San Francisco; San Francisco General Hospital (SFGH)
Publications:

Layout table for additonal information
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01276236    
Other Study ID Numbers: 11351
2860798 ( Other Identifier: FDA IND Exemption Reference ID )
First Posted: January 13, 2011    Key Record Dates
Results First Posted: March 5, 2021
Last Update Posted: March 5, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of California, San Francisco:
Kaposi's Sarcoma
Maraviroc
CCR5
HIV
Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma, Kaposi
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Neoplasms, Vascular Tissue
Maraviroc
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
CCR5 Receptor Antagonists