HIV InfectionsPhase 2NCT00021489
Mycophenolate Mofetil and Abacavir Treatment in HIV Patients With Failed Anti-HIV Treatment
A Phase 2 study testing Abacavir sulfate and Mycophenolate mofetil in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID).
Trial summary
The purpose of this study is to learn how safe and well-tolerated mycophenolate mofetil (MMF) is when given with abacavir (ABC). Another purpose is to see if adding MMF to ABC decreases viral load (amount of HIV in the blood) more than ABC alone. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Abacavir sulfate and Mycophenolate mofetil
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento not given
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients may be eligible for this study if they:
- Are HIV infected.
- Have a CD4 cell count of at least 100 cells/microL.
- Have a viral load (amount of virus in the blood) of at least 2,000 copies/ml obtained within 30 days prior to study entry.
- Have had exposure to all 3 classes of anti-HIV drugs (2 or more NRTIs for at least 12 months each, 2 or more PIs for at least 6 months each, and 1 or more NNRTIs for at least 3 months).
- Have not changed an NNRTI or PI in their anti-HIV drugs in the 30 days prior to study entry.
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- Have a negative pregnancy test within 7 days prior to study entry.
- Agree to use 2 accepted birth control methods while on the study and for 6 weeks after stopping the drugs, if participating in sexual activity that could lead to pregnancy.
- Are at least 13 years of age.
- Have consent of parent or guardian if under 18 years of age.
- Start preventive treatment for Pneumocystis carinii pneumonia (PCP) within 30 days prior to study entry, if CD4 cell count is below 200 cells/microL.
Who cannot join
- Patients will not be eligible for this study if they:
- Use ABC, hydroxyurea, metronidazole, MMF, or ribavirin within 30 days prior to study entry.
- Are allergic to ABC or MMF.
- Have had prior CMV infection in any organs.
- Have had Kaposi's sarcoma.
- Have had a herpes infection within 3 months prior to study entry, or have had more than 3 outbreaks of herpes in a year, or have had more than 1 outbreak of herpes despite preventive treatment.
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- Have had ulcers within 1 year of entering the study.
- Abuse alcohol or drugs.
- Are breast-feeding.
- Use certain drugs that may interfere with the study within 30 days prior to study entry.
- Have a serious illness that may interfere with their entering the study.
About this study
Official title: A Phase I/II Study of the Safety, Tolerability, and Antiretroviral Activity of Mycophenolate Mofetil As an Adjunct to Abacavir Therapy in HIV-Infected Subjects With Treatment Failure and Extensive Prior Antiretroviral Exposure
The purpose of this study is to learn how safe and well-tolerated mycophenolate mofetil (MMF) is when given with abacavir (ABC). Another purpose is to see if adding MMF to ABC decreases viral load (amount of HIV in the blood) more than ABC alone.
Many HIV-infected patients who have had heavy exposure to anti-HIV drugs and have experienced treatment failure need new treatment combinations. One promising combination is ABC and MMF as part of a drug combination. Laboratory studies show that MMF helps ABC destroy HIV in the cells and further clinical testing is needed. MMF is not FDA-approved as a treatment for HIV infection but has been approved by FDA to prevent rejection of organ transplants. Doses of MMF tested in this study will be lower than those used to treat people with organ transplants.
Read the detailed description
A large group of heavily drug-exposed HIV-infected individuals with detectable HIV-1 RNA exists as a result of the sequential use and failure of existing antiretroviral agents from each of the 3 antiretroviral drug classes (nucleoside reverse transcriptase inhibitors [NRTIs], protease inhibitors [PIs], and nonnucleoside reverse transcriptase inhibitors [NNRTIs]). Systematic approaches are needed to define "salvage therapy" regimens for this patient group. This trial uses a short-term study to determine the initial safety, pharmacology, and antiviral potency of MMF in augmenting the antiretroviral effect of ABC, which then can be appraised for use as a salvage regimen. After rapid oral absorption, MMF is hydrolyzed to form MPA (mycophenolic acid), the active metabolite. Recent in vitro studies show that MPA concentrations as low as 62.5 nM synergistically increase the antiviral effect of ABC or ddI, or of ABC in combination with ddI, against multinucleoside-resistant HIV strains. These observations suggest that MMF in combination with ABC might play a role in antiretroviral therapy in patients with drug resistance, and continued clinical evaluation of MMF is warranted.
At study entry, patients stop current NRTIs but continue taking PIs and NNRTIs with study treatment. The first 50 patients are stratified by plasma HIV-1 RNA (below 40,000 copies/ml or 40,000 and higher copies/ml) and randomized to either Arm A or Arm B. Arm A receives ABC with MMF placebo; Arm B receives ABC and MMF. Only ABC and MMF are provided by the study. Treatment is received for 4 weeks and patients are evaluated for safety, tolerability, and virologic response. At Week 4, entry genotype results are provided to patients and antiretroviral therapy may then be altered as indicated. Patients are unblinded to study treatment as soon as possible after Week 4 but no later than Week 7. Future opening of Arm C to 125 additional patients is delayed until the first 50 patients have reached Week 4 and an interim review of safety and virologic response is completed. Responders may continue study treatment through Week 24. At 10 clinic visits patients have blood drawn for HIV-1 RNA determinations, CD4 and CD8 cell counts, and genotyping. Patients may participate in pharmacokinetic substudy A5121s.
- Conditions
- HIV Infections
- Being tested
- Abacavir sulfate, Mycophenolate mofetil
- Keywords
- Placebos, Drug Therapy, Combination, Reverse Transcriptase Inhibitors, Anti-HIV Agents, abacavir, mycophenolate mofetil
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abacavir sulfateDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Masking
- Double blind
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David Margolis, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00021489
- Sponsor's protocol ID
- A5105
- Other IDs
- 10927, ACTG A5105, AACTG A5105, Substudy AACTG A5121s
- Status last verified
- Oct 2021
- First submitted
- 18 Jul 2001
- Last updated
- 1 Nov 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of the Safety, Tolerability, and Antiretroviral Activity of Mycophenolate Mofetil As an Adjunct to Abacavir Therapy in HIV-Infected Subjects With Treatment Failure and Extensive Prior Antiretroviral Exposure
- ClinicalTrials.gov ID
- NCT00021489
- Acronym / sponsor ID
- A5105
- Conditions
- HIV Infections
- Keywords
- Placebos, Drug Therapy, Combination, Reverse Transcriptase Inhibitors, Anti-HIV Agents, abacavir, mycophenolate mofetil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn how safe and well-tolerated mycophenolate mofetil (MMF) is when given with abacavir (ABC). Another purpose is to see if adding MMF to ABC decreases viral load (amount of HIV in the blood) more than ABC alone.
Many HIV-infected patients who have had heavy exposure to anti-HIV drugs and have experienced treatment failure need new treatment combinations. One promising combination is ABC and MMF as part of a drug combination. Laboratory studies show that MMF helps ABC destroy HIV in the cells and further clinical testing is needed. MMF is not FDA-approved as a treatment for HIV infection but has been approved by FDA to prevent rejection of organ transplants. Doses of MMF tested in this study will be lower than those used to treat people with organ transplants.
Detailed description
A large group of heavily drug-exposed HIV-infected individuals with detectable HIV-1 RNA exists as a result of the sequential use and failure of existing antiretroviral agents from each of the 3 antiretroviral drug classes (nucleoside reverse transcriptase inhibitors [NRTIs], protease inhibitors [PIs], and nonnucleoside reverse transcriptase inhibitors [NNRTIs]). Systematic approaches are needed to define "salvage therapy" regimens for this patient group. This trial uses a short-term study to determine the initial safety, pharmacology, and antiviral potency of MMF in augmenting the antiretroviral effect of ABC, which then can be appraised for use as a salvage regimen. After rapid oral absorption, MMF is hydrolyzed to form MPA (mycophenolic acid), the active metabolite. Recent in vitro studies show that MPA concentrations as low as 62.5 nM synergistically increase the antiviral effect of ABC or ddI, or of ABC in combination with ddI, against multinucleoside-resistant HIV strains. These observations suggest that MMF in combination with ABC might play a role in antiretroviral therapy in patients with drug resistance, and continued clinical evaluation of MMF is warranted.
At study entry, patients stop current NRTIs but continue taking PIs and NNRTIs with study treatment. The first 50 patients are stratified by plasma HIV-1 RNA (below 40,000 copies/ml or 40,000 and higher copies/ml) and randomized to either Arm A or Arm B. Arm A receives ABC with MMF placebo; Arm B receives ABC and MMF. Only ABC and MMF are provided by the study. Treatment is received for 4 weeks and patients are evaluated for safety, tolerability, and virologic response. At Week 4, entry genotype results are provided to patients and antiretroviral therapy may then be altered as indicated. Patients are unblinded to study treatment as soon as possible after Week 4 but no later than Week 7. Future opening of Arm C to 125 additional patients is delayed until the first 50 patients have reached Week 4 and an interim review of safety and virologic response is completed. Responders may continue study treatment through Week 24. At 10 clinic visits patients have blood drawn for HIV-1 RNA determinations, CD4 and CD8 cell counts, and genotyping. Patients may participate in pharmacokinetic substudy A5121s.
Study design
- Primary purpose
- Treatment
- Masking
- Double blind
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Are HIV infected.
- Have a CD4 cell count of at least 100 cells/microL.
- Have a viral load (amount of virus in the blood) of at least 2,000 copies/ml obtained within 30 days prior to study entry.
- Have had exposure to all 3 classes of anti-HIV drugs (2 or more NRTIs for at least 12 months each, 2 or more PIs for at least 6 months each, and 1 or more NNRTIs for at least 3 months).
- Have not changed an NNRTI or PI in their anti-HIV drugs in the 30 days prior to study entry.
Key exclusion criteria (11 listed)
- Use ABC, hydroxyurea, metronidazole, MMF, or ribavirin within 30 days prior to study entry.
- Are allergic to ABC or MMF.
- Have had prior CMV infection in any organs.
- Have had Kaposi's sarcoma.
- Have had a herpes infection within 3 months prior to study entry, or have had more than 3 outbreaks of herpes in a year, or have had more than 1 outbreak of herpes despite preventive treatment.
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 |
|---|---|---|
| Abacavir sulfate | Drug | – |
| Mycophenolate mofetil | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
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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.
David Margolis study chair
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abacavir sulfate and Mycophenolate mofetil in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID).
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 11 inclusion and 11 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: withdrawn, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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.
Where can I read the original study information?
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 1 Nov 2021.