HIV InfectionPhase 2IL2NCT03308786
HIV Reservoir Reduction With Interleukin-2
A Phase 2 study testing Recombinant Interleukin-2 in people with HIV Infection, run by Case Western Reserve University at 1 site in United States.
Trial summary
The purpose of this pilot study is to examine the effects of eight 4-day cycles of subcutaneous recombinant interleukin-2 (rIL-2) given every 8 weeks on levels of replication-competent HIV in CD4 cells and on the size of HIV viral reservoir in up to 20 participants with chronically suppressed HIV infection (viral load… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infection
- What is being tested?
- Recombinant Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2019to 20 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent signed and dated by study participant.
- Male or female, at least 18 years of age and not older than 65 years of age.
- HIV-1 infection, documented by and FDA-approved ELISA, EIA, or rapid antibody detection method, and confirmed by a second approved antibody-based test or by a positive approved HIV RNA detection assay.
- CD4+ T cell count ≥ 350 cells/mm3;
- HIV-1 RNA < 50 copies/mL obtained within 60 days prior to study entry performed with an FDA-approved HIV-1 RNA assay.
- Adequate venous access and no other contraindications for leukapheresis
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- Absolute neutrophil count (ANC) > 2000/mm3
- Hemoglobin level >10 g/dL (males); > 9.5 g/dL (females)
- Platelet count >150,000/mm3
- Serum creatinine <1.5 mg/dL
- AST and ALT <2.5 times the upper limit of normal
- TSH, T3, and T4 levels within the normal range of the processing laboratory.
- Anti-thyrosine peroxidase (TPO) within the normal range of the processing laboratory.
- Willing to comply with study-mandated evaluations; including not changing antiretroviral regimen (unless medically indicated) during the study period.
- All participants must have received HAART, and had viral loads below the limit of quantification of the assay for at least 1 year. Participants who had intermittent isolated episodes of detectable low-level viremia < 500 copies RNA/mL flanked by viral loads below the limit of quantification of the assay will remain eligible.
- On a stable 3-drug combination antiretroviral regimen (no changes to treatment within 4 weeks of enrollment) and willing to continue on current antiretroviral therapy for the duration of the study, unless otherwise medically indicated. The study principal investigator can approve a 2-drug antiretroviral regimen on a case-by-case basis.
Who cannot join
- Childbearing potential for female participants. For the purposes of this study, a woman is considered to be of childbearing potential if she is postmenarche, has not had a documented surgical sterilization procedure, has an intact uterus and at least 1 ovary, and has had a spontaneous menstrual period in the last 2 years.
- Acute or chronic hepatitis C infection, defined as a positive plasma HCV RNA using any FDA-approved qualitative or quantitative test in a participant with a positive HCV antibody (HCV RNA testing is not required in participants with a negative HCV antibody). Participants who have completed a course of a direct-acting antiviral agent for hepatitis C and have a confirmed plasma HCV RNA level below the limit of detection of the assay 12 weeks or longer after completion of therapy will be eligible.
- Acute or chronic hepatitis B infection, defined as a positive HBV surface antigen or a positive HBV DNA.
- History of advanced chronic liver disease, including cirrhosis, advanced liver fibrosis, severe portal hypertension, or manifestations or hepatic failure.
- History of malignant disease that is not considered to be surgically or medically eradicated or that has required any form of therapy in the past 5 years.
- Current diagnosis of congestive heart failure of any severity, uncontrolled angina or uncontrolled arrhythmias.
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- History of chronic lung disease that has required pharmacologic treatment, oxygen supplementation, medical monitoring, or hospitalization in the previous year, or that is expected to cause persistent or recurrent pulmonary symptoms or impairment. Examples of the latter include but are not limited to chronic bronchitis, emphysema, and pulmonary fibrosis.
- History or any features on physical examination indicative of a bleeding diathesis.
- History or current diagnosis of thromboembolic disease, including deep vein thrombosis and pulmonary embolism, or family history of the same.
- History of hypersensitivity to radiological contrast media or anticipated need for exposure to radiological contrast media during the study period.
- Use of chronic corticosteroids, hydroxyurea, or immune-modulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to enrollment.
- NOTE: Use of inhaled or topical steroids is not exclusionary.
- Breast-feeding.
- Use of aspirin, warfarin or any other antithrombotic or antiplatelet agent during the 2-week period prior to leukapheresis.
- History of autoimmune disorders, including but not limited to Crohn's disease, scleroderma, thyroiditis, inflammatory arthritis, myasthenia gravis, glomerulonephritis, systemic lupus erythematous, and vasculitis.
- Type 1 diabetes mellitus.
- History of thyroid disease that has required antithyroid or thyroid hormone replacement therapy at any time in the past.
- Current continued use, or anticipated continued medical indication for nephrotoxic agents, including but not limited to aminoglycosides and other potentially nephrotoxic antimicrobials, indomethacin, high scheduled doses of other NSAIDs, and lithium salts.
- NOTE: Low doses or limited duration of these agents (i.e., ≤14 days) is not exclusionary.
- Current continued use, or anticipated continued medical indication for hepatotoxic agents, including but not limited to amiodarone, methotrexate, and anticonvulsants and antimicrobials with elevated hepatotoxic potential.
- NOTE: Low doses or limited duration of these agents (i.e., ≤14 days) is not exclusionary.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry that in the judgement of the investigator may compromise study participation or pose additional risks to the participant.
- Any other condition that, in the opinion of the clinical investigator or sponsor, might compromise any aspect of this trial.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this pilot study is to examine the effects of eight 4-day cycles of subcutaneous recombinant interleukin-2 (rIL-2) given every 8 weeks on levels of replication-competent HIV in CD4 cells and on the size of HIV viral reservoir in up to 20 participants with chronically suppressed HIV infection (viral load <50 copies/mL).
Read the detailed description
Interleukin-2 (IL-2) has been extensively studied in HIV infected individuals with no demonstrated clinical benefit as far as improving survival or decreasing risk of progression to AIDS. The results of the two landmark, international, multicenter, phase III, randomized trials of IL-2 in HIV infected participants (SILCAAT and ESPRIT) have been recently published. These trials, which started more than a decade ago, enrolled over 5800 participants who were randomized to anti-retroviral therapy (ART) +/- IL-2 and showed no benefit to IL-2 treatment in survival or progression to AIDS. Many individuals with HIV infection can lead normal lives on ART but replication-competent virus remains within resting CD4+ cells, referred to as the "HIV reservoir". There is a renewed interest in strategies to decrease or eliminate the viral reservoir in an attempt to provide a sterilizing or a functional "cure" for HIV that would allow the discontinuation of ART, which currently must be taken life-long. These therapies have long-term metabolic and cardiovascular toxicities as well as substantial cost. More recent data suggest that IL-2 administration may decrease the size of the HIV reservoir, getting ART-treated participants closer to levels of HIV persistence that may ultimately allow for sterilizing or functional cure.
The purpose of this pilot study is to examine the effects of eight 4-day cycles of subcutaneous recombinant interleukin-2 (rIL-2) given every 8 weeks on levels of replication-competent HIV in CD4 cells and on the size of HIV viral reservoir in up to 20 participants with chronically suppressed HIV infection (viral load <50 copies/mL).
- Conditions
- HIV Infection
- Being tested
- Recombinant Interleukin-2
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Interleukin-2Drug
Also called IL2, IL-2, rIL2, aldesleukin
Subcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles
| Study group | Role | What they receive |
|---|---|---|
| IL2 treatment | Experimental | Subcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles, in addition to combination antiretroviral therapy. Receives: Drug: Recombinant Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Latent HIV Reservoir Change by QVOA
Change in the number of infectious units per million resting CD4+ T cells (IUPM) from baseline to the end of study treatment, as measured by the Quantitative Viral Outgrowth Assay (QVOA).
Measured: 15 months
Secondary outcomes (7)
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by Intact Proviral DNA.
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the intact proviral DNA assay.
Measured: 15 months
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by the Tat-rev Inducible Limiting Dilution Assay (TILDA).
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the Tat-rev inducible limiting dilution assay (TILDA).
Measured: 15 months
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by the Envelope Detection by Induced Transcription-based Sequencing (EDITS)
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the Envelope Detection by Induced Transcription-based Sequencing (EDITS).
Measured: 15 months
In Vivo Induction of HIV Expression in Vivo as Measured by the Envelope Detection by Induced Transcription-based Sequencing (EDITS)
Number of inducible cell-associated HIV mRNA copies per million CD4+ T cells at the beginning and end of rIL2 cycles 1, 4, and 8.
Measured: 15 months
Plasma HIV RNA During rIL2 Exposure
Plasma HIV RNA copies/mL by PCR at the beginning and end of rIL2 cycle 1.
Measured: baseline, day 7
Natural Killer (NK) Cell Phenotype During rIL2 Exposure
Change in the percent of NK cells expressing CD16+CD56+ by flow cytometry from baseline to the end of study treatment.
Measured: baseline, day 7
Natural Killer (NK) Cell Phenotype During rIL2 Exposure
Change in the percent of NK cells expressing CD56+CD16- by flow cytometry from baseline to the end of study treatment.
Measured: baseline, day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2017
- Study start1 Apr 2019
- Primary completion20 Aug 2020
- Study completion20 Aug 2020
Why it stopped: There were 3 instances of adverse events which were discussed with external safety monitoring committee and it was recommended that the study be terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Western Reserve University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael M. Lederman MD, Case Western Reserve University
- Investigators
- Benigno Rodriguez, MD, Study chair, Case Western Reserve UniversityMichael Lederman, MD, Study chair, Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03308786
- Sponsor's protocol ID
- AIDS 400: IL2
- Acronym
- IL2
- Status last verified
- Sep 2022
- First submitted
- 29 Sep 2017
- Last updated
- 28 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HIV Reservoir Reduction With Interleukin-2
- ClinicalTrials.gov ID
- NCT03308786
- Acronym / sponsor ID
- IL2 / AIDS 400: IL2
- Conditions
- HIV Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: There were 3 instances of adverse events which were discussed with external safety monitoring committee and it was recommended that the study be terminated.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Case Western Reserve UniversityUniversity, hospital or other
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 20 Aug 2020 (actual)
- Study completion
- 20 Aug 2020 (actual)
- First posted
- 13 Oct 2017 (actual)
- Results
- Posted 28 Sep 2022
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 pilot study is to examine the effects of eight 4-day cycles of subcutaneous recombinant interleukin-2 (rIL-2) given every 8 weeks on levels of replication-competent HIV in CD4 cells and on the size of HIV viral reservoir in up to 20 participants with chronically suppressed HIV infection (viral load <50 copies/mL).
Detailed description
Interleukin-2 (IL-2) has been extensively studied in HIV infected individuals with no demonstrated clinical benefit as far as improving survival or decreasing risk of progression to AIDS. The results of the two landmark, international, multicenter, phase III, randomized trials of IL-2 in HIV infected participants (SILCAAT and ESPRIT) have been recently published. These trials, which started more than a decade ago, enrolled over 5800 participants who were randomized to anti-retroviral therapy (ART) +/- IL-2 and showed no benefit to IL-2 treatment in survival or progression to AIDS. Many individuals with HIV infection can lead normal lives on ART but replication-competent virus remains within resting CD4+ cells, referred to as the "HIV reservoir". There is a renewed interest in strategies to decrease or eliminate the viral reservoir in an attempt to provide a sterilizing or a functional "cure" for HIV that would allow the discontinuation of ART, which currently must be taken life-long. These therapies have long-term metabolic and cardiovascular toxicities as well as substantial cost. More recent data suggest that IL-2 administration may decrease the size of the HIV reservoir, getting ART-treated participants closer to levels of HIV persistence that may ultimately allow for sterilizing or functional cure.
The purpose of this pilot study is to examine the effects of eight 4-day cycles of subcutaneous recombinant interleukin-2 (rIL-2) given every 8 weeks on levels of replication-competent HIV in CD4 cells and on the size of HIV viral reservoir in up to 20 participants with chronically suppressed HIV infection (viral load <50 copies/mL).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IL2 treatment | Experimental | Drug: Recombinant Interleukin-2Subcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles, in addition to combination antiretroviral therapy. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Written informed consent signed and dated by study participant.
- Male or female, at least 18 years of age and not older than 65 years of age.
- HIV-1 infection, documented by and FDA-approved ELISA, EIA, or rapid antibody detection method, and confirmed by a second approved antibody-based test or by a positive approved HIV RNA detection assay.
- CD4+ T cell count ≥ 350 cells/mm3;
- HIV-1 RNA < 50 copies/mL obtained within 60 days prior to study entry performed with an FDA-approved HIV-1 RNA assay.
Key exclusion criteria (24 listed)
- Childbearing potential for female participants. For the purposes of this study, a woman is considered to be of childbearing potential if she is postmenarche, has not had a documented surgical sterilization procedure, has an intact uterus and at least 1 ovary, and has had a spontaneous menstrual period in the last 2 years.
- Acute or chronic hepatitis C infection, defined as a positive plasma HCV RNA using any FDA-approved qualitative or quantitative test in a participant with a positive HCV antibody (HCV RNA testing is not required in participants with a negative HCV antibody). Participants who have completed a course of a direct-acting antiviral agent for hepatitis C and have a confirmed plasma HCV RNA level below the limit of detection of the assay 12 weeks or longer after completion of therapy will be eligible.
- Acute or chronic hepatitis B infection, defined as a positive HBV surface antigen or a positive HBV DNA.
- History of advanced chronic liver disease, including cirrhosis, advanced liver fibrosis, severe portal hypertension, or manifestations or hepatic failure.
- History of malignant disease that is not considered to be surgically or medically eradicated or that has required any form of therapy in the past 5 years.
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 |
|---|---|---|
| Recombinant Interleukin-2Also: IL2, IL-2, rIL2, aldesleukinSubcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles | Drug | IL2 treatment |
Primary outcome
Latent HIV Reservoir Change by QVOA
Time frame: 15 months
Change in the number of infectious units per million resting CD4+ T cells (IUPM) from baseline to the end of study treatment, as measured by the Quantitative Viral Outgrowth Assay (QVOA).
7 secondary outcomes
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by Intact Proviral DNA.
Time frame: 15 months
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by the Tat-rev Inducible Limiting Dilution Assay (TILDA).
Time frame: 15 months
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by the Envelope Detection by Induced Transcription-based Sequencing (EDITS)
Time frame: 15 months
In Vivo Induction of HIV Expression in Vivo as Measured by the Envelope Detection by Induced Transcription-based Sequencing (EDITS)
Time frame: 15 months
Plasma HIV RNA During rIL2 Exposure
Time frame: baseline, day 7
Natural Killer (NK) Cell Phenotype During rIL2 Exposure
Time frame: baseline, day 7
Natural Killer (NK) Cell Phenotype During rIL2 Exposure
Time frame: baseline, day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Benigno Rodriguez, MD study chair
Case Western Reserve University
Michael Lederman, MD study chair
Case Western Reserve University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Recombinant Interleukin-2 in people with HIV Infection, run by Case Western Reserve University at 1 site 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 16 inclusion and 24 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: stopped early, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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?
Yes. Results are posted in the registry (first posted 28 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Latent HIV Reservoir Change by QVOA (time frame: 15 months). It is what the study was designed to measure, not a finding.
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 28 Sep 2022.