A Study of DAPD Alone Versus DAPD Plus MMF for Treatment of HIV Infection

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase I/II Randomized, Double-Blind, Placebo-Controlled Pilot Study of Beta-D-2,6-diaminopurine Dioxolane (DAPD) Versus DAPD Plus Mycophenolate Mofetil (MMF) in Treatment-Experienced Subjects

The purpose of this study is to evaluate the safety, efficacy, and side effects of beta-D-2,6-diaminopurine dioxolane (DAPD) compared to DAPD plus mycophenolate mofetil (MMF) when these drugs are added to the anti-HIV treatment regimens of people infected with HIV.

Some studies have shown that DAPD and MMF can help fight HIV. However, neither DAPD nor MMF has been approved by the Food and Drug Administration for treating HIV infection. This study will help doctors decide if DAPD and MMF are good drugs for treating HIV.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The antiretroviral potency of DAPD varies among antiretroviral-experienced patients. In vitro studies indicate that the potency of DAPD can be markedly increased by the addition of MMF. Preliminary data indicate that MMF is well tolerated in patients with advanced HIV-1 disease. However, there is currently no clinical data on the activity of DAPD combined with MMF. This study will be the first to evaluate the addition of DAPD and MMF to a patient's current antiretroviral therapy.

At study entry, patients will be randomly assigned to one of two blinded treatment arms. Arm A receives DAPD plus MMF placebo in addition to their current regimen, while Arm B receives DAPD plus MMF in addition to their current regimen. All patients remain on their current antiretroviral regimen through Week 2. After Week 2, patients who virologically respond are encouraged to remain on blinded study treatment through Week 24. Patients who do not virologically respond are unblinded.

After unblinding, patients who were not receiving MMF may add it to their antiretroviral regimen. Response to the addition of open-label MMF is assessed after 2 weeks. Resistance to antiretroviral agents, including DAPD, will be assessed following any virologic failure occurring after Week 2. All patients have the option of optimizing their background antiretroviral regimen at Week 2, based on the results of a pre-entry resistance assay; enfuvirtide will be made available for background therapy optimization through Week 48.

Patients who are still receiving DAPD alone or DAPD plus MMF at Week 48 and who are still responding virologically may choose to continue the study drug(s) and be followed for up to an additional 48 weeks. Throughout the study, HIV-1 RNA levels, CD4 cell counts, and study drug levels will be monitored regularly. Eye exams will be done at several study visits. Only DAPD, MMF, and MMF placebo will be supplied by this study; patients must obtain the rest of their treatment regimen through their doctor. Patients who discontinue treatment before the end of study will need to come in for a follow-up visit 4 weeks after discontinuation and may need to attend future follow-up visits at 8-week intervals, as determined by the investigator.

Study Type

Interventional

Enrollment

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095-1793
        • UCLA CARE Center CRS
      • Palo Alto, California, United States, 943055107
        • Stanford CRS
      • Sacramento, California, United States, 95814
        • UC Davis Medical Center
      • Sacramento, California, United States, 95814
        • Univ. of California Davis Med. Ctr., ACTU
    • Colorado
      • Aurora, Colorado, United States, 80262
        • University of Colorado Hospital CRS
    • Florida
      • Miami, Florida, United States, 33136-1013
        • Univ. of Miami AIDS CRS
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ. of Hawaii at Manoa, Leahi Hosp.
    • Maryland
      • Baltimore, Maryland, United States
        • Johns Hopkins Adult AIDS CRS
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455-0392
        • University of Minnesota, ACTU
    • Missouri
      • Saint Louis, Missouri, United States, 63108-2138
        • Washington U CRS
    • New York
      • New York, New York, United States, 10003
        • Beth Israel Med. Ctr., ACTU
      • New York, New York, United States, 10016
        • NY Univ. HIV/AIDS CRS
    • Ohio
      • Cleveland, Ohio, United States, 44106-5083
        • Case CRS
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hosp. of the Univ. of Pennsylvania CRS
      • Philadelphia, Pennsylvania, United States, 19401
        • Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
      • Pittsburgh, Pennsylvania, United States, 15213
        • Pitt CRS
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington AIDS CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria for Step 1:

  • HIV infected
  • Triple-class antiretroviral treatment, as determined by the site investigator and as defined by all of the following: a) exposure to 2 or more nucleotide reverse transcriptase inhibitors (NRTIs) for at least 3 months each; b) exposure to 2 or more non-boosted protease inhibitors (PIs) for at least 3 months each, or exposure to a dual PI regimen for at least 3 months; and c) exposure to at least 1 non-nucleotide reverse transcriptase inhibitor (NNRTI) for at least 3 months.
  • CD4 cell count of at least 50 cells/mm3 within 45 days prior to study entry
  • Viral load of 2000 copies/ml or more within 45 days prior to study entry
  • On current antiretroviral treatment regimen for at least 30 days prior to study entry. If current treatment includes abacavir, abacavir must be discontinued at least 30 days prior to study entry.
  • Willing to use acceptable methods of contraception

Exclusion Criteria for Step 1:

  • Pregnant or breastfeeding
  • Allergy or sensitivity to the study drugs and their formulations
  • Diabetes mellitus
  • Cataracts or any measurable loss of vision due to lens opacity
  • Best-corrected visual acuity worse than 20/200
  • Certain drugs or vaccines within 30 days prior to study entry
  • History of any of the following: kidney disease; serious illness within 14 days prior to study entry; end organ cytomegalovirus infection; Kaposi's sarcoma; cataracts; active herpetic infection or peptic ulcer disease within 12 months; or malabsorption, severe chronic diarrhea, or inability to eat 1 or more meals a day because of chronic nausea, emesis, or abdominal/mouth and throat discomfort
  • Current alcohol or drug abuse that would interfere with adherence to study requirements

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: David Margolis, MD, Division of Infectious Diseases, University of Texas Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

April 1, 2006

Study Registration Dates

First Submitted

May 29, 2002

First Submitted That Met QC Criteria

May 29, 2002

First Posted (Estimate)

May 30, 2002

Study Record Updates

Last Update Posted (Actual)

November 1, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A5165
  • 10090 (Registry Identifier: DAIDS ES)
  • ACTG A5165
  • AACTG A5165

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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