Human Immunodeficiency Virus I InfectionPhase 2NCT03262441
MMF for HIV Reservoir Reduction
A Phase 2 study testing Mycophenolate Mofetil 500Mg Tab in people with Human Immunodeficiency Virus I Infection, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
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: 1. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Human Immunodeficiency Virus I Infection
- What is being tested?
- Mycophenolate Mofetil 500Mg Tab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Feb 2018to 31 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed HIV infection, by two different positive antibody tests and/or detectable plasma HIV RNA on two different dates
- ≥18 and ≤65 years of age
- Continuous ART during the last two years, with current ART preferably including an integrase inhibitor
- HIV RNA <40 copies / mL on four occasions during continuous ART of ≥ 2 years with no more than one blip of <1000 HIV RNA copies / mL
- CD4+ T cell count > 350/mm3 within the past 365 days
- Karnofsky score ≥80
Show all 10Show fewer
- Plan to reside in area 2 years
- Consents to study
- Tolerability of MMF during one week dose escalation lead-in phase of 500 mg once daily
- Demonstrated anti-proliferative effect of MMF 500 mg twice daily
Who cannot join
- Active malignancy including skin cancer, myelodysplastic syndrome, or myeloproliferative disease within 24 weeks prior to study entry
- Prior organ or bone marrow transplantation
- Diagnosed autoimmune disease
- Medical need for ongoing treatment with an immunosuppressive drug
- Diagnosis of AIDS (defined as any AIDS-defining opportunistic infection or cancer, or a history of blood CD4+ T cell count < 200/µL)
- Active opportunistic infection
Show all 20Show fewer
- Using disallowed medications (see 4.3)
- Vomiting or diarrhea which prohibits consistent use of study drugs
- Pregnant, intention to become pregnant, or breastfeeding
- Woman of child bearing age who are NOT using two forms of birth control OR practicing complete abstinence
- Excessive ingestion of ethanol, determined by an AUDIT score of >8
- Substance abuse
- History of medical non-compliance
- Quantiferon TB positive
- The following laboratory values (< 30 days before enrollment):
- Hemoglobin < 8.5 mg/dL
- Absolute neutrophil count < 1000 cells/mm3
- ALT > 2 x upper limit of normal
- Platelet count < 100,000/uL
- Creatinine clearance < 60 mL/min
Trial locations and contacts
1 site in 1 country.
United States1 site
2 West Clinic at Harborview Medical Center
Seattle, Washington, 98104
About this study
Official title: Mycophenolate Mofetil Therapy for Reduction of the HIV Reservoir
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.
Read the detailed 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.
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.
- Conditions
- Human Immunodeficiency Virus I Infection
- Being tested
- Mycophenolate Mofetil 500Mg Tab
- Keywords
- HIV, Antiretroviral treatment, Mycophenolate mofetil, Cure, Latency, Reservoir, CD4 T cell, Anti-proliferation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mycophenolate Mofetil 500Mg TabDrug
Also called Mycophenolate Mofetil Tablets USP Roxane Laboratories
500 mg once daily for one week. If tolerating the drug, then initiate twice daily for 22 months
| Study group | Role | What they receive |
|---|---|---|
| Mycophenolate mofetil | Experimental | 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 Receives: Drug: Mycophenolate Mofetil 500Mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 T Cells Over 12 Months
Regression slope of change in cell-associated HIV DNA (ca-DNA) as measured by multiplexed digital droplet PCR in study participants on MMF calculated from 4 time points between 0 \& 12 months
Measured: 12 months
Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 Effector Memory CD4+ T Cells Over 12 Months
Regression slope of change in cell-associated HIV DNA (ca-DNA) as measured by multiplexed digital droplet PCR in study participants on MMF calculated from 3 time points between 0 \& 12 months
Measured: 12 months
Change in Cell-associated Intact HIV DNA (Ca-iDNA) Levels Per 10^6 T Cells Over 12 Months
Regression slope of change in cell-associated intact HIV DNA (ca-iDNA) as measured by multiplexed digital droplet PCR in study participants on MMF calculated from 4 time points between 0 \& 12 months
Measured: 12 months
Secondary outcomes (2)
Blood CD4+ T Cells Per mm^3 Blood
Frequency of participants with any time point with <200 CD4+ T cells per mm^3 from 4 sampled time points between 0 \& 12 months
Measured: 12 months
Incidence of Opportunistic Infection
Number of participants experiencing opportunistic infection
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2017
- Study start12 Feb 2018
- Primary completion31 Aug 2019
- Study completion31 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency Virus I InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Washington
- Responsible party
- Principal investigator, Joshua Schiffer, Fred Hutchinson Cancer Center
- Investigators
- Joshua T Schiffer, MD MSc, Principal investigator, Fred Hutchinson Cancer CenterFlorian Hladik, MD PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03262441
- Sponsor's protocol ID
- 8589
- Other IDs
- STUDY00002182, 109614-62-RGRL, ACTU-2100
- Status last verified
- Nov 2020
- First submitted
- 23 Aug 2017
- Last updated
- 3 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Reeves DB, Duke ER, Hughes SM, Prlic M, Hladik F, Schiffer JT. Anti-proliferative therapy for HIV cure: a compound interest approach. Sci Rep. 2017 Jun 21;7(1):4011. doi: 10.1038/s41598-017-04160-3.
PubMed 28638104Schiffer JT, Levy C, Hughes SM, Pandey U, Padullo M, Jerome KR, Zhu H, Puckett K, Helgeson E, Harrington RD, Hladik F. Stable HIV Reservoir Despite Prolonged Low-Dose Mycophenolate to Limit CD4+ T-cell Proliferation. Open Forum Infect Dis. 2022 Nov 19;9(12):ofac620. doi: 10.1093/ofid/ofac620. eCollection 2022 Dec.
PubMed 36519118
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mycophenolate Mofetil Therapy for Reduction of the HIV Reservoir
- ClinicalTrials.gov ID
- NCT03262441
- Acronym / sponsor ID
- 8589
- Conditions
- Human Immunodeficiency Virus I Infection
- Keywords
- HIV, Antiretroviral treatment, Mycophenolate mofetil, Cure, Latency, Reservoir, CD4 T cell, Anti-proliferation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- University of Washington
- Study start
- 12 Feb 2018 (actual)
- Primary completion
- 31 Aug 2019 (actual)
- Study completion
- 31 Aug 2019 (actual)
- First posted
- 25 Aug 2017 (actual)
- Results
- Posted 3 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Mycophenolate mofetil | Experimental | Drug: Mycophenolate Mofetil 500Mg TabMycophenolate 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Confirmed HIV infection, by two different positive antibody tests and/or detectable plasma HIV RNA on two different dates
- ≥18 and ≤65 years of age
- Continuous ART during the last two years, with current ART preferably including an integrase inhibitor
- HIV RNA <40 copies / mL on four occasions during continuous ART of ≥ 2 years with no more than one blip of <1000 HIV RNA copies / mL
- CD4+ T cell count > 350/mm3 within the past 365 days
Key exclusion criteria (20 listed)
- Active malignancy including skin cancer, myelodysplastic syndrome, or myeloproliferative disease within 24 weeks prior to study entry
- Prior organ or bone marrow transplantation
- Diagnosed autoimmune disease
- Medical need for ongoing treatment with an immunosuppressive drug
- Diagnosis of AIDS (defined as any AIDS-defining opportunistic infection or cancer, or a history of blood CD4+ T cell count < 200/µL)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate Mofetil 500Mg TabAlso: Mycophenolate Mofetil Tablets USP Roxane Laboratories500 mg once daily for one week. If tolerating the drug, then initiate twice daily for 22 months | Drug | Mycophenolate mofetil |
Primary outcome
Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 T Cells Over 12 Months
Time frame: 12 months
Regression slope of change in cell-associated HIV DNA (ca-DNA) as measured by multiplexed digital droplet PCR in study participants on MMF calculated from 4 time points between 0 \& 12 months
Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 Effector Memory CD4+ T Cells Over 12 Months
Time frame: 12 months
Regression slope of change in cell-associated HIV DNA (ca-DNA) as measured by multiplexed digital droplet PCR in study participants on MMF calculated from 3 time points between 0 \& 12 months
Change in Cell-associated Intact HIV DNA (Ca-iDNA) Levels Per 10^6 T Cells Over 12 Months
Time frame: 12 months
Regression slope of change in cell-associated intact HIV DNA (ca-iDNA) as measured by multiplexed digital droplet PCR in study participants on MMF calculated from 4 time points between 0 \& 12 months
2 secondary outcomes
Blood CD4+ T Cells Per mm^3 Blood
Time frame: 12 months
Incidence of Opportunistic Infection
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28638104Reeves DB, Duke ER, Hughes SM, Prlic M, Hladik F, Schiffer JT. Anti-proliferative therapy for HIV cure: a compound interest approach. Sci Rep. 2017 Jun 21;7(1):4011. doi: 10.1038/s41598-017-04160-3.
- Derived from this study: PubMed 36519118Schiffer JT, Levy C, Hughes SM, Pandey U, Padullo M, Jerome KR, Zhu H, Puckett K, Helgeson E, Harrington RD, Hladik F. Stable HIV Reservoir Despite Prolonged Low-Dose Mycophenolate to Limit CD4+ T-cell Proliferation. Open Forum Infect Dis. 2022 Nov 19;9(12):ofac620. doi: 10.1093/ofid/ofac620. eCollection 2022 Dec.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joshua T Schiffer, MD MSc principal investigator
Fred Hutchinson Cancer Center
Florian Hladik, MD PhD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycophenolate Mofetil 500Mg Tab in people with Human Immunodeficiency Virus I Infection, run by Fred Hutchinson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 T Cells Over 12 Months (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03262441, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2020; AzTrials last refreshed its copy on 31 Oct 2026.