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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00038272
• Other study ID #: A5165
• Secondary ID: 10090ACTG A5165A
• Status: Completed
• Phase: Phase 2
• Est. completion date: April 2006

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: April 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infections

Intervention

Drug:
• Mycophenolate mofetil

• Amdoxovir

Locations

Country	Name	City	State
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Case CRS	Cleveland	Ohio
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	UCLA CARE Center CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	University of Minnesota, ACTU	Minneapolis	Minnesota
United States	Beth Israel Med. Ctr., ACTU	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Stanford CRS	Palo Alto	California
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.	Philadelphia	Pennsylvania
United States	Pitt CRS	Pittsburgh	Pennsylvania
United States	UC Davis Medical Center	Sacramento	California
United States	Univ. of California Davis Med. Ctr., ACTU	Sacramento	California
United States	Washington U CRS	Saint Louis	Missouri
United States	University of Washington AIDS CRS	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Chapuis AG, Paolo Rizzardi G, D'Agostino C, Attinger A, Knabenhans C, Fleury S, Acha-Orbea H, Pantaleo G. Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo. Nat Med. 2000 Jul;6(7):762-8. — View Citation

Coull JJ, Turner D, Melby T, Betts MR, Lanier R, Margolis DM. A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection. J Acquir Immune Defic Syndr. 2001 Apr 15;26(5):423-34. — View Citation

Gulick RM. New antiretroviral drugs. Clin Microbiol Infect. 2003 Mar;9(3):186-93. Review. — View Citation

Rizzardi GP, Lazzarin A, Pantaleo G. Potential role of immune modulation in the effective long-term control of HIV-1 infection. J Biol Regul Homeost Agents. 2002 Jan-Mar;16(1):83-90. Review. — View Citation

External Links

•   Haga clic aquí para ver información sobre este ensayo clínico en español.