NCT03262441

MMF for HIV Reservoir Reduction

Completed Phase 2 Results posted Last updated 3 December 2020

What this trial tests

Phase 2 trial testing Mycophenolate Mofetil 500Mg Tab in Human Immunodeficiency Virus I Infection in 5 participants. Completed in 31 August 2019.

Timeline

12 February 2018

Primary endpoint
31 August 2019

31 August 2019

Quick facts

Lead sponsor	Fred Hutchinson Cancer Center
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	5
Start date	12 February 2018
Primary completion	31 August 2019
Estimated completion	31 August 2019
Sites	1 location across United States

Drugs / interventions tested

• Mycophenolate Mofetil 500Mg Tab — full drug profile →

Conditions studied

• Human Immunodeficiency Virus I Infection — all drugs for Human Immunodeficiency Virus I Infection →

Sponsor

Fred Hutchinson Cancer Center — full company profile →

Who can join

Adults 18 to 65, any sex, with Human Immunodeficiency Virus I Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 T Cells Over 12 Months Primary · 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

Group	Value	95% CI
Mycophenolate Mofetil	-0.00033	-0.0020 – 0.0014

Change in Cell-associated HIV DNA (Ca-DNA) Levels Per 10^6 Effector Memory CD4+ T Cells Over 12 Months Primary · 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

Group	Value	95% CI
Mycophenolate Mofetil	0.001	-0.0036 – 0.0056

Change in Cell-associated Intact HIV DNA (Ca-iDNA) Levels Per 10^6 T Cells Over 12 Months Primary · 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

Group	Value	95% CI
Mycophenolate Mofetil	.0024	-0.0030 – 0.0078

Blood CD4+ T Cells Per mm^3 Blood Secondary · 12 months

Frequency of participants with any time point with \<200 CD4+ T cells per mm\^3 from 4 sampled time points between 0 \& 12 months

Group	Value	95% CI
Mycophenolate Mofetil	0

Incidence of Opportunistic Infection Secondary · 12 months

Number of participants experiencing opportunistic infection

Group	Value	95% CI
Mycophenolate Mofetil	0

Adverse events — posted to ClinicalTrials.gov

Time frame: 20 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Mycophenolate Mofetil

Serious: 1/5 (20%)

Deaths: 0/5

Serious adverse events (1 terms)

Reaction	System	Mycophenolate Mofetil
Finger cellulitis	Skin and subcutaneous tissue disorders	—

Most-reported serious reactions: Finger cellulitis.

Data from ClinicalTrials.gov NCT03262441 adverse events section.

Sponsor's own description

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. MMF will be well tolerated and will not decrease adherence to or antiviral efficacy of ART.
2. Peripheral CD4+ T-cell counts and percentages will not meaningfully decrease during treatment with MMF and ART.
3. There will be no excess risk of opportunistic infections in MMF-treated study participants.
4. MMF therapy will lead to a progressive decrease in reservoir size over 22 months of treatment.
5. 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.
6. MMF will eliminate detectable measures of the HIV reservoir, including by cell-associated DNA/mRNA and quantitative viral outgrowth.
7. MMF will not decrease the humoral immune response to routine annual influenza vaccination.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Single-cell transcriptional landscapes reveal HIV-1-driven aberrant host gene transcription as a potential therapeutic target.
   Liu R, Yeh YJ, Varabyou A, Collora JA, et al · · 2020 · cited 101× · PMID 32404504 · DOI 10.1126/scitranslmed.aaz0802
2. A highly multiplexed droplet digital PCR assay to measure the intact HIV-1 proviral reservoir.
   Levy CN, Hughes SM, Roychoudhury P, Reeves DB, et al · · 2021 · cited 84× · PMID 33948574 · DOI 10.1016/j.xcrm.2021.100243
3. The forces driving clonal expansion of the HIV-1 latent reservoir.
   Liu R, Simonetti FR, Ho YC. · · 2020 · cited 67× · PMID 31910871 · DOI 10.1186/s12985-019-1276-8
4. Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation.
   Yeh YJ, Jenike KM, Calvi RM, Chiarella J, et al · · 2020 · cited 39× · PMID 32573496 · DOI 10.1172/jci137371
5. Nanotechnology approaches to eradicating HIV reservoirs.
   Cao S, Woodrow KA. · · 2019 · cited 37× · PMID 29879528 · DOI 10.1016/j.ejpb.2018.06.002
6. Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.
   Li X, Peng T. · · 2021 · cited 25× · PMID 34017257 · DOI 10.3389/fphar.2021.660710
7. Pediatric HIV: the Potential of Immune Therapeutics to Achieve Viral Remission and Functional Cure.
   Berendam SJ, Nelson AN, Goswami R, Persaud D, et al · · 2020 · cited 18× · PMID 32356090 · DOI 10.1007/s11904-020-00495-1
8. Investigational drugs with dual activity against HBV and HIV (Review).
   Sun S, Yang Q, Sheng Y, Fu Y, et al · · 2021 · cited 7× · PMID 33262821 · DOI 10.3892/etm.2020.9467