MMF for HIV Reservoir Reduction
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|ClinicalTrials.gov Identifier: NCT03262441|
Recruitment Status : Recruiting
First Posted : August 25, 2017
Last Update Posted : February 6, 2018
This is an open label, randomized Phase II study to determine whether Mycophenolate mofetil (MMF) given over 22 months meaningfully decreases the size of participants' HIV reservoir.
In addition to primary safety endpoints, the following hypotheses regarding drug efficacy will be tested:
- MMF will be well tolerated and will not decrease adherence to or antiviral efficacy of ART.
- Peripheral CD4+ T-cell counts and percentages will not meaningfully decrease during treatment with MMF and ART.
- There will be no excess risk of opportunistic infections in MMF-treated study participants.
- MMF therapy will lead to a progressive decrease in reservoir size over 22 months of treatment.
- MMF therapy will lead to a continual shift in HIV reservoir composition from primarily effector memory CD4+ T cells (TEM) and central memory CD4+ T cells (TCM), to primarily stem cell like memory (TSCM) and naïve (TN) CD4+ T cells.
- MMF will eliminate detectable measures of the HIV reservoir, including by cell-associated DNA/mRNA and quantitative viral outgrowth.
- MMF will not decrease the humoral immune response to routine annual influenza vaccination.
|Condition or disease||Intervention/treatment||Phase|
|Human Immunodeficiency Virus I Infection||Drug: Mycophenolate Mofetil 500Mg Tab||Phase 2|
This is an open-label, randomized pilot trial to determine whether MMF given over 22 months meaningfully decreases the size of the HIV reservoir.
At the University of Washington in Seattle, investigators will enroll 5 study participants who have been on ≥2 years of suppressive ART. Study participants will be followed closely for at least 22 months with safety labs and serial measurements of the HIV reservoir (specifically, cell-associated HIV DNA and mRNA (ca-DNA & ca-RNA), quantitative viral outgrowth assay (QVOA), and single copy plasma viral load (scVL)). A "go/no-go" decision will occur after 12 months based on pre-defined thresholds of reduction in the HIV reservoir measured with ca-DNA.
All participants will be offered enrollment in a sub-study in which an anoscopy with rectum biopsies is performed on 3 occasions to assess the reservoir in the gastrointestinal lymphatic tissue (GALT).
Investigators will vaccinate study participants with the annual influenza vaccine and analyze their humoral response to this vaccine approximately one month later with a routine blood draw done in conjunction with a safety labs blood draw.
Investigators hypothesize that low doses of MMF will be well tolerated among healthy HIV-infected study participants who have fully ART-suppressed HIV. Investigators hypothesize that the incidence of opportunistic infections will not exceed that of comparable larger cohorts of HIV-treated patients. Of note, certain opportunistic infections such as herpes zoster or HSV-2 recurrence continue to occur despite suppressive ART, while pneumocystis pneumonia, CMV end organ disease, cryptococcus and many other opportunistic infections are much less common in this context. Therefore, in the event of an infection, Investigators will confer with the data safety management (DSM) panel to discuss whether this event is directly attributable to MMF. Finally, investigators hypothesize that peripheral blood CD4+ and CD8+ T cell counts will remain unchanged throughout MMF therapy, and that HIV replication will remain controlled on ART with addition of MMF.
Investigators hypothesize at least a 0.25-log reduction in cell-associated HIV DNA at one-year intervals in study participants who have a demonstrated anti-proliferative response to MMF treatment. Investigators hypothesize that cell-associated HIV DNA will undergo a shift from predominant residence in TCM and TEM to predominant residence in TN and TSCM. In regards to our sub-study, investigators predict that reservoir depletion will occur with equivalent rates in blood and GALT.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is an open-label, randomized pilot trial to determine whether MMF given over 22 months meaningfully decreases the size of the HIV reservoir. Study participants will be followed closely for at least 22 months with safety labs and serial measurements of the HIV reservoir (specifically, cell-associated HIV DNA and mRNA (ca-DNA & ca-RNA), quantitative viral outgrowth assay (QVOA), and single copy plasma viral load (scVL)). "Go/no-go" decision will occur after 12 months based on pre-defined thresholds of reduction in the HIV reservoir measured with ca-DNA.|
|Masking:||None (Open Label)|
|Official Title:||Mycophenolate Mofetil Therapy for Reduction of the HIV Reservoir|
|Actual Study Start Date :||January 1, 2018|
|Estimated Primary Completion Date :||August 31, 2019|
|Estimated Study Completion Date :||August 31, 2020|
Experimental: Mycophenolate mofetil
Mycophenolate Mofetil 500mg Tablets once per day for one week as a lead in to limit drug-related side effects. Provided they are tolerating the drug at lower dose, they will then initiate Mycophenolate Mofetil 500mg Tablets twice daily orally for 22 months
Drug: Mycophenolate Mofetil 500Mg Tab
500 mg once daily for one week. If tolerating the drug, then initiate twice daily for 22 months
Other Name: Mycophenolate Mofetil Tablets USP Roxane Laboratories
- Change in frequency of cells containing integrated HIV DNA [ Time Frame: 22 months ]Change in cell-associated HIV DNA (ca-DNA) reservoir size as measured by multiplexed digital droplet PCR in study participants on versus off MMF (historical controls)
- Change in HIV plasma viral load [ Time Frame: 22 months ]Change in HIV replication by single copy viral load (scVL) in study participants on versus off MMF (historical controls).
- Change of HIV reactivation [ Time Frame: 22 months ]Change of viral reactivation by cell-associated HIV mRNA in study participants on versus off MMF (historical controls)
- Change of inducible HIV reservoir size [ Time Frame: 22 months ]Change of the inducible HIV reservoir size by quantitative viral outgrowth assay (QVOA) in study participants on versus off MMF (historical controls).
- Change of the cellular composition of the HIV DNA reservoir [ Time Frame: 22 months ]Change of the cellular composition of the HIV DNA reservoir in study participants on versus off MMF (historical controls).
- Blood CD4+ T cells [ Time Frame: 22 months ]Blood CD4+ T cell count
- Thymic generation of new CD4+ T cells [ Time Frame: 22 months ]CD4+ T cell numbers that recently emigrated from the thymus
- Complete blood cell count [ Time Frame: 22 months ]Complete blood cell count, comprehensive metabolic panel
- Incidence of opportunistic infection [ Time Frame: 22 months ]Incidence of opportunistic infection
- Antibody response to annual influenza vaccination [ Time Frame: 22 months ]Antibody response to annual influenza vaccination
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): NCT03262441
|Contact: Joshua T Schiffer, MD MScemail@example.com|
|Contact: Florian Hladik, MD PhDfirstname.lastname@example.org|
|United States, Washington|
|2 West Clinic at Harborview Medical Center||Recruiting|
|Seattle, Washington, United States, 98104|
|Contact: Mel Padullo 206-744-8884|
|Contact: Eric Helgeson 206-744-8883|
|Principal Investigator: Joshua Schiffer, MD, MS|
|Principal Investigator: Florian Hladik, MD, PhD|
|Sub-Investigator: Robert Harrington, MD|
|Principal Investigator:||Joshua T Schiffer, MD MSc||Fred Hutchinson Cancer Research Center|
|Principal Investigator:||Florian Hladik, MD PhD||University of Washington|