HIV InfectionsPhase 1/2NCT00011011
Vaccine (ALVAC-HIV vCP1452) Use and Intermittent Withdrawal of Anti-HIV Drugs in Patients With HIV
A Phase 1/2 study testing ALVAC(2)120(B,MN)GNP (vCP1452) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 16 sites in United States.
Trial summary
Long-term control of HIV depends on improvement in an individual's immune system. The purpose of this study is to see if either stopping anti-HIV drugs for short periods of time and/or adding a vaccine to the anti-HIV drugs being taken will help to better control HIV infection. 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?
- ALVAC(2)120(B,MN)GNP (vCP1452)
- How many people
- 94 participants
- Where
- 16 sitesUnited States
- Study dates
- Feb 2001to Oct 2006
- Phase
- Phase 1/2
- 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
- HIV infection
- CD4 count greater than 400 cells/mm3 within 6 months before study entry
- Current, persistent viral load below 400 copies/ml for 6 months before study entry and under 50 copies/ml at study screening
- Currently receiving their first combination ART regimen (3 or more antiretrovirals) for at least 4 weeks before screening, or if the current potent ART regimen is not their first potent ART regimen, must have been receiving the current regimen for at least 4 weeks prior to screening
- Negative pregnancy test within 45 days before study entry
- Acceptable methods of contraception
- Provide informed consent
Who cannot join
- Immunomodulators within 45 days of study entry such as systemic corticosteroids, interferons, interleukins, thalidomide, sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]), dinitrochlorobenzene (DNCB), thymosin alpha, thymopentin, inosiplex, polyribonucleoside, and ditiocarb sodium
- Abacavir within 8 weeks of study entry
- Infection or medical illness within 14 days of study entry
- Cancer that may require systemic therapy
- History of lymph node radiation therapy
- Prior HIV vaccine
Show all 15Show fewer
- Received hydroxyurea within 45 days of study entry
- Close contact with canaries through work (e.g., breeding farms, bird shops); patients with a pet canary are not excluded
- Abuse or dependence on drugs or alcohol
- Allergic to albumin
- Pregnant or breastfeeding
- Infected with HIV within 1 year of study entry
- Interruption of potent ART for more than 7 consecutive days within 1 year of study entry
- History of allergy to egg proteins or neomycin
- History of other serious acute allergic reactions (e.g., anaphylaxis, allergy-induced asthma, Stevens-Johnson syndrome, toxic epidermal necrolysis)
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Alabama Therapeutics CRS
Birmingham, Alabama, 35294
Unc Aids Crs
Chapel Hill, North Carolina, 27599
Case CRS
Cleveland, Ohio, 44106
The Ohio State University Medical Center
Columbus, Ohio, 43210
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202
UCLA CARE Center CRS
Los Angeles, California, 90095
Beth Israel Med. Ctr., ACTU
New York, New York, 10003
NY Univ. HIV/AIDS CRS
New York, New York, 10016
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104
Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
Philadelphia, Pennsylvania, 19104
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, 02906
AIDS Care CRS
Rochester, New York, 14607
Univ. of Rochester ACTG CRS
Rochester, New York, 14642
Ucsf Aids Crs
San Francisco, California, 94110
University of Washington AIDS CRS
Seattle, Washington, 98104
Washington U CRS
St Louis, Missouri, 63110
About this study
Official title: A Randomized Phase I/II Pilot Study of Intermittent Withdrawal of Antiretroviral Therapy as an Immunization Strategy and Double-Blinded Immunization With ALVAC-HIV vCP1452 in Subjects With Persistent CD4+ Cell Counts Greater Than 400 Cells/mm3 and Plasma HIV-1 RNA Levels Less Than 50 Copies/ml
Long-term control of HIV depends on improvement in an individual's immune system. The purpose of this study is to see if either stopping anti-HIV drugs for short periods of time and/or adding a vaccine to the anti-HIV drugs being taken will help to better control HIV infection. The study will test whether these treatment approaches are safe. The HIV vaccine in this study has been tested in people who did not have HIV infection and improved the way their immune system worked. This study will evaluate whether these same immune system changes happen in people with HIV, and, if such changes do occur, assess whether these changes help to improve control of HIV in these patients.
Read the detailed description
The best hope for long-term control of HIV infection in an individual likely rests with the resumption of effective HIV-specific immune responses. Intermittent antiretroviral therapy (ART) withdrawal, as an attempt to "immunize" the subject with his/her own active viral quasi-species population, represents an alternative approach to traditional immunization strategies. This study hopes to determine whether intermittent ART withdrawal serves to stimulate HIV-specific immune responses and control of viral replication. This approach will be compared with vaccination with ALVAC-HIV vCP1452. In addition, it is conceivable that intermittent ART withdrawal could boost and broaden the prime response to exogenous vaccine; that will also be studied.
Patients will continue receiving their potent ART (not provided by the study) and will be randomly assigned to one of four treatment strategies as follows:
Arm A: ALVAC placebo and potent ART for 92 weeks with a single 12- to 20-week therapy withdrawal period; Arm B: ALVAC placebo and potent ART for 84 weeks with a 4- to 6-week therapy withdrawal period, a 4-week therapy withdrawal period, and a 12- to 20-week therapy withdrawal period; Arm C: ALVAC vCP1452 vaccine and potent ART for 92 weeks with a single 12- to 20-week therapy withdrawal period; and Arm D: ALVAC vCP1452 vaccine and potent ART for 84 weeks with a 4- to 6-week therapy withdrawal period, a 4-week therapy withdrawal period, and a 12- to 20-week therapy withdrawal period.
Immunizations of placebo or vaccine wil be administered in 3 separate sets of 3 injections per set (9 total) and immunization schedules are the same for all patients, those undergoing intermittent therapy withdrawal (Arms B and D) and those who are not (Arms A and C).
This is a multiple-step study. Patients in Arms B and D will receive a 4-week period of potent ART therapy along with the first set of immunizations (Step 1) followed by therapy withdrawal for 4 to 6 weeks (Step 2). Alternating periods of therapy resumption (Step 3, consisting of 16 weeks on potent ART with the second set of vaccine administrations), a second therapy withdrawal (Step 4 for 4 weeks), and another therapy resumption (Step 5, consisting of 16 weeks on potent ART with the third set of vaccine administrations) will follow. Patients in Arms A and C will remain on Step 1 for the first 44 weeks on study.
After 44 to 46 weeks on study, patients in all arms will have therapy withdrawn for 12 to 20 weeks (Step 6). Following completion of Step 6, patients whose viral load are below 10,000 copies/ml will be encouraged to remain off potent ART (Step 7) until completion of the study, as long as CD4 T-cell levels remain 50 percent or more of their baseline levels. Participants who successfully complete Step 7 will be invited to enter Step 9, a 48-week optional protocol extension. Otherwise, patients will restart their potent ART regimens (Step 8) and receive virologic and CD4 T-cell monitoring until completion of the study.
All patients will be monitored at regular clinic visits. Viral load and CD4 T-cell counts will be measured at each visit. Patients in all arms may participate in substudy A5101s (Male Genital Secretions) or substudy A5137s (Female Genital Secretions), and patients in Arms B and D may participate in substudy A5111s (Latent Infected T-Cell Clearance).
- Conditions
- HIV Infections
- Being tested
- ALVAC(2)120(B,MN)GNP (vCP1452)
- Keywords
- HIV-1, Drug Administration Schedule, AIDS Vaccines, CD4 Lymphocyte Count, RNA, Viral, Anti-HIV Agents, Viral Load, HIV Therapeutic Vaccine, Treatment Interruption
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALVAC(2)120(B,MN)GNP (vCP1452)Biological
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)
- Study startFeb 2001
- Study completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jeffrey M. Jacobson, MD, Study chair, Beth Israel Medical CenterIan Frank, MD, Study chair, Division of Infectious Diseases, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00011011
- Sponsor's protocol ID
- A5068
- Other IDs
- 10072, Substudy AACTG A5101s, Substudy AACTG A5111s, Substudy AACTG A5137s, ACTG A5068, AACTG A5068
- Status last verified
- Oct 2021
- First submitted
- 8 Feb 2001
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
Ferrari G, Berend C, Ottinger J, Dodge R, Bartlett J, Toso J, Moody D, Tartaglia J, Cox WI, Paoletti E, Weinhold KJ. Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy. Blood. 1997 Sep 15;90(6):2406-16.
PubMed 9310492Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science. 1997 Nov 21;278(5342):1447-50. doi: 10.1126/science.278.5342.1447.
PubMed 9367954Belshe RB, Gorse GJ, Mulligan MJ, Evans TG, Keefer MC, Excler JL, Duliege AM, Tartaglia J, Cox WI, McNamara J, Hwang KL, Bradney A, Montefiori D, Weinhold KJ. Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group. AIDS. 1998 Dec 24;12(18):2407-15. doi: 10.1097/00002030-199818000-00009.
PubMed 9875578Jacobson JM, Pat Bucy R, Spritzler J, Saag MS, Eron JJ Jr, Coombs RW, Wang R, Fox L, Johnson VA, Cu-Uvin S, Cohn SE, Mildvan D, O'Neill D, Janik J, Purdue L, O'Connor DK, Vita CD, Frank I; National Institute of Allergy and Infectious Diseases-AIDS Clinical Trials Group 5068 Protocol Team. Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: the results of AIDS Clinical Trials Group 5068. J Infect Dis. 2006 Sep 1;194(5):623-32. doi: 10.1086/506364. Epub 2006 Aug 1.
PubMed 16897661
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 Randomized Phase I/II Pilot Study of Intermittent Withdrawal of Antiretroviral Therapy as an Immunization Strategy and Double-Blinded Immunization With ALVAC-HIV vCP1452 in Subjects With Persistent CD4+ Cell Counts Greater Than 400 Cells/mm3 and Plasma HIV-1 RNA Levels Less Than 50 Copies/ml
- ClinicalTrials.gov ID
- NCT00011011
- Acronym / sponsor ID
- A5068
- Conditions
- HIV Infections
- Keywords
- HIV-1, Drug Administration Schedule, AIDS Vaccines, CD4 Lymphocyte Count, RNA, Viral, Anti-HIV Agents, Viral Load, HIV Therapeutic Vaccine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Feb 2001
- Study completion
- Oct 2006 (actual)
- 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.
Long-term control of HIV depends on improvement in an individual's immune system. The purpose of this study is to see if either stopping anti-HIV drugs for short periods of time and/or adding a vaccine to the anti-HIV drugs being taken will help to better control HIV infection. The study will test whether these treatment approaches are safe. The HIV vaccine in this study has been tested in people who did not have HIV infection and improved the way their immune system worked. This study will evaluate whether these same immune system changes happen in people with HIV, and, if such changes do occur, assess whether these changes help to improve control of HIV in these patients.
Detailed description
The best hope for long-term control of HIV infection in an individual likely rests with the resumption of effective HIV-specific immune responses. Intermittent antiretroviral therapy (ART) withdrawal, as an attempt to "immunize" the subject with his/her own active viral quasi-species population, represents an alternative approach to traditional immunization strategies. This study hopes to determine whether intermittent ART withdrawal serves to stimulate HIV-specific immune responses and control of viral replication. This approach will be compared with vaccination with ALVAC-HIV vCP1452. In addition, it is conceivable that intermittent ART withdrawal could boost and broaden the prime response to exogenous vaccine; that will also be studied.
Patients will continue receiving their potent ART (not provided by the study) and will be randomly assigned to one of four treatment strategies as follows:
Arm A: ALVAC placebo and potent ART for 92 weeks with a single 12- to 20-week therapy withdrawal period; Arm B: ALVAC placebo and potent ART for 84 weeks with a 4- to 6-week therapy withdrawal period, a 4-week therapy withdrawal period, and a 12- to 20-week therapy withdrawal period; Arm C: ALVAC vCP1452 vaccine and potent ART for 92 weeks with a single 12- to 20-week therapy withdrawal period; and Arm D: ALVAC vCP1452 vaccine and potent ART for 84 weeks with a 4- to 6-week therapy withdrawal period, a 4-week therapy withdrawal period, and a 12- to 20-week therapy withdrawal period.
Immunizations of placebo or vaccine wil be administered in 3 separate sets of 3 injections per set (9 total) and immunization schedules are the same for all patients, those undergoing intermittent therapy withdrawal (Arms B and D) and those who are not (Arms A and C).
This is a multiple-step study. Patients in Arms B and D will receive a 4-week period of potent ART therapy along with the first set of immunizations (Step 1) followed by therapy withdrawal for 4 to 6 weeks (Step 2). Alternating periods of therapy resumption (Step 3, consisting of 16 weeks on potent ART with the second set of vaccine administrations), a second therapy withdrawal (Step 4 for 4 weeks), and another therapy resumption (Step 5, consisting of 16 weeks on potent ART with the third set of vaccine administrations) will follow. Patients in Arms A and C will remain on Step 1 for the first 44 weeks on study.
After 44 to 46 weeks on study, patients in all arms will have therapy withdrawn for 12 to 20 weeks (Step 6). Following completion of Step 6, patients whose viral load are below 10,000 copies/ml will be encouraged to remain off potent ART (Step 7) until completion of the study, as long as CD4 T-cell levels remain 50 percent or more of their baseline levels. Participants who successfully complete Step 7 will be invited to enter Step 9, a 48-week optional protocol extension. Otherwise, patients will restart their potent ART regimens (Step 8) and receive virologic and CD4 T-cell monitoring until completion of the study.
All patients will be monitored at regular clinic visits. Viral load and CD4 T-cell counts will be measured at each visit. Patients in all arms may participate in substudy A5101s (Male Genital Secretions) or substudy A5137s (Female Genital Secretions), and patients in Arms B and D may participate in substudy A5111s (Latent Infected T-Cell Clearance).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- 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 (7 listed)
- HIV infection
- CD4 count greater than 400 cells/mm3 within 6 months before study entry
- Current, persistent viral load below 400 copies/ml for 6 months before study entry and under 50 copies/ml at study screening
- Currently receiving their first combination ART regimen (3 or more antiretrovirals) for at least 4 weeks before screening, or if the current potent ART regimen is not their first potent ART regimen, must have been receiving the current regimen for at least 4 weeks prior to screening
- Negative pregnancy test within 45 days before study entry
Key exclusion criteria (15 listed)
- Immunomodulators within 45 days of study entry such as systemic corticosteroids, interferons, interleukins, thalidomide, sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]), dinitrochlorobenzene (DNCB), thymosin alpha, thymopentin, inosiplex, polyribonucleoside, and ditiocarb sodium
- Abacavir within 8 weeks of study entry
- Infection or medical illness within 14 days of study entry
- Cancer that may require systemic therapy
- History of lymph node radiation therapy
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 |
|---|---|---|
| ALVAC(2)120(B,MN)GNP (vCP1452) | Biological | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Background: PubMed 9310492Ferrari G, Berend C, Ottinger J, Dodge R, Bartlett J, Toso J, Moody D, Tartaglia J, Cox WI, Paoletti E, Weinhold KJ. Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy. Blood. 1997 Sep 15;90(6):2406-16.
- Background: PubMed 9367954Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science. 1997 Nov 21;278(5342):1447-50. doi: 10.1126/science.278.5342.1447.
- Background: PubMed 9875578Belshe RB, Gorse GJ, Mulligan MJ, Evans TG, Keefer MC, Excler JL, Duliege AM, Tartaglia J, Cox WI, McNamara J, Hwang KL, Bradney A, Montefiori D, Weinhold KJ. Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group. AIDS. 1998 Dec 24;12(18):2407-15. doi: 10.1097/00002030-199818000-00009.
- Results publication: PubMed 16897661Jacobson JM, Pat Bucy R, Spritzler J, Saag MS, Eron JJ Jr, Coombs RW, Wang R, Fox L, Johnson VA, Cu-Uvin S, Cohn SE, Mildvan D, O'Neill D, Janik J, Purdue L, O'Connor DK, Vita CD, Frank I; National Institute of Allergy and Infectious Diseases-AIDS Clinical Trials Group 5068 Protocol Team. Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: the results of AIDS Clinical Trials Group 5068. J Infect Dis. 2006 Sep 1;194(5):623-32. doi: 10.1086/506364. Epub 2006 Aug 1.
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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.
Jeffrey M. Jacobson, MD study chair
Beth Israel Medical Center
Ian Frank, MD study chair
Division of Infectious Diseases, University of Pennsylvania
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ALVAC(2)120(B,MN)GNP (vCP1452) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 16 sites 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 7 inclusion and 15 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 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
On the ClinicalTrials.gov record for NCT00011011, which also lists 4 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 1 Nov 2021.