HIV InfectionPhase 1/2ACTIVATENCT02471430
Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy
A Phase 1/2 study testing Panobinostat and Pegylated Interferon-alpha2a in people with HIV Infection, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study is a prospective, open-label, randomized, three-arm, dose-escalation exploratory pilot clinical trial involving HIV-1 infected participants treated with suppressive combination antiretroviral combination therapy (cART). 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?
- Panobinostat and Pegylated Interferon-alpha2a
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to Dec 2023
- Phase
- Phase 1/2
- 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
- Ability and willingness to provide informed consent
- HIV-1 infection prior to entry
- Receiving suppressive ART therapy for a minimum of 24 consecutive months prior to screening with no interruption of therapy (same ART regimen for at least 12 weeks prior to screening)
- Documented suppressed HIV-1 RNA (plasma HIV-1 RNA values <50 copies/ml)
- CD4 T cell count ≥ 400 cells/mm3
- Negative Hepatitis B surface antigen (HBsAg) or Negative HBV DNA PCR
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- Negative anti-Hepatitis C virus antibodies (anti-HCV) or negative HCV PCR if anti-HCV antibodies are positive
- Negative TB Test (if positive, completed a recommended treatment course for latent TB)
- Vaccinated for pneumococcal disease within last 5 years
- No clinically significant eye disease
- No evidence of clinical coronary heart disease
- Not pregnant, planning to become pregnant, or breastfeeding
- Willingness to continue to use contraceptives for 90 days after completing treatment
- If male, willingness to use a condom during intercourse while taking panobinostat and total of 80 hours after stopping treatment
- Not pregnant, planning to become pregnant, or breastfeeding
- No evidence of coronary heart disease
Who cannot join
- HIV-1 RNA > 50 copies/mL within 24 months of screening
- Severe psychiatric disease, chronic liver disease, past or current evidence of immunologically mediated disease
- Severe retinopathy due to diabetes, hypertension, cytomegalovirus or macular degeneration
- Evidence of coronary heart disease
- History of active thyroid disease requiring medication
- Breastfeeding
Show all 18Show fewer
- Presence of a bacterial, fungal, viral or protozoal infection requiring systemic anti-infective therapy
- Uncontrolled seizure disorders
- History or other evidence of severe illness or other conditions
- History of malignancy of any organ system within the past 5 years
- Female participants who are pregnant or nursing
- History of solid organ transplantation with an existing functional graft
- Use of any immunomodulatory agents within 30 days prior to study enrollment or planned use during the trial
- Active drug or alcohol use or dependence
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the participant in case of participation in the study
- Use of HIV protease inhibitor or other strong or moderately strong CYP3A4 inhibitors
- History of anaphylaxis, allergy or serious adverse reactions to Interferon-alpha2a/Interferon-alpha2b or panobinostat
- Has taken: interleukins, systemic interferons or systemic chemotherapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, 02114
About this study
Official title: A Phase I-II Pilot Study to Assess the Safety and Efficacy of Combined Administration With Pegylated Interferon-alpha2a and the Histone Deacetylase Inhibitor (HDACi) Panobinostat for Reducing the Residual Reservoir of HIV-1 Infected Cells in cART-Treated HIV-1 Positive Individuals
This study is a prospective, open-label, randomized, three-arm, dose-escalation exploratory pilot clinical trial involving HIV-1 infected participants treated with suppressive combination antiretroviral combination therapy (cART). The study will test whether combined treatment with the histone deacetylase inhibitor panobinostat and the immunomodulatory cytokine Interferon-alpha2a can reduce the residual reservoir of HIV-1 infected cells that persist during treatment with currently available antiretroviral drugs.
Read the detailed description
This study is a prospective, triple-arm, randomized, open-label, dose-escalation exploratory clinical trial involving HIV-1 infected participants treated with suppressive combination antiretroviral combination therapy (cART). The primary objective of this study is to evaluate a new strategy for reducing the residual reservoir of HIV-1 infected cells that persists despite treatment with current HIV drugs. The clinical trial is conducted in the Infectious Diseases Clinical Trials Unit (CTU) at the Massachusetts General Hospital.
The study medication includes two agents: panobinostat is an oral tablet that can reverse HIV-1 latency and awaken HIV from a "sleeping" condition during which it is protected from the human immune system. The second drug is pegylated interferon-alpha2a (IFN-alpha2a), an injectable cytokine that activates the immune system. The combined use of both agents may lead to immune-mediated elimination of HIV-1 infected cells in which viral latency has been reversed by panobinostat.
Participants will be randomized to receive a treatment course with panobinostat alone (Arm A, 4 participants total), panobinostat in combination with pegylated IFN-alpha2a (Arm B, 9 participants total), or pegylated IFN-alpha2a alone (Arm C, 4 participants total). Participants receiving panobinostat will undergo one week of treatment (15mg, dosed every second day on Monday, Wednesday, Friday), followed by three weeks off-treatment. Subcutaneous injections with pegylated IFN-alpha2a will be administered at the start of the week-long treatment course (simultaneously with the first dose of panobinostat for Arm B). ART will be continued during the entire treatment duration in all study participants.
Participants will undergo close monitoring for side effects during the entire time of study participation. The total study duration will be 2 months.
- Conditions
- HIV Infection
- Being tested
- Panobinostat, Pegylated Interferon-alpha2a
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called Farydak, LBH589
Panobinostat will be administered orally.
Pegylated Interferon-alpha2aDrug
Also called Pegasys
Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet. Receives: Drug: Panobinostat |
| Arm B | Experimental | Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week. Receives: Drug: Panobinostat; Drug: Pegylated Interferon-alpha2a |
| Arm C | Experimental | Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg. Receives: Drug: Pegylated Interferon-alpha2a |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Grade ≥ 1 Adverse Events (AEs)
Cumulative frequency and severity of Grade ≥ 1 adverse events, Grade ≥ 1 lab abnormalities or serious adverse events
Measured: All adverse events measured from day 1 until day 28 after administration of the first dose of panobinostat and/or interferon-alpha2a was recorded.
Change in CD4 T Cell-Associated Proviral HIV-1 DNA From Baseline
Operational measurement of CD4 T cells harboring genome-intact HIV-1 DNA, determined by the IPDA assay.
Measured: Measured through week 4 after administration of panobinostat and/or interferon-alpha2a
Secondary outcomes (3)
Change From Baseline in Histone H3 Acetylation in CD4 T Cells
CD4 T cells expressing acetylated H3, determined by flow cytometry.
Measured: measured after last dose of PBT on day 4
Change From Baseline in Levels of CD4 T Cell-associated HIV-1 RNA
total HIV-1 RNA per ug of RNA in CD4 T cells
Measured: measured after last dose of PBT on day 4
Change From Baseline in Frequency of Activated NKp30+ NK Cells.
the proportion of NK cells expressing NKp30
Measured: measured after last dose of PBT on day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startMay 2016
- Primary completionAug 2022
- Study completionDec 2023
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Genentech, Inc.
- Responsible party
- Principal investigator, Mathias Lichterfeld, Massachusetts General Hospital
- Investigators
- Mathias Lichterfeld, MD, PhD, Principal investigator, Massachusetts General HospitalDaniel R Kuritzkes, MD, Principal investigator, Massachusetts General HospitalRajesh T Gandhi, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02471430
- Sponsor's protocol ID
- U01 2015P000858
- Other IDs
- 12049
- Acronym
- ACTIVATE
- Status last verified
- Feb 2024
- First submitted
- 11 Jun 2015
- Last updated
- 28 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, Winckelmann A, Palmer S, Dinarello C, Buzon M, Lichterfeld M, Lewin SR, Ostergaard L, Sogaard OS. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV. 2014 Oct;1(1):e13-21. doi: 10.1016/S2352-3018(14)70014-1. Epub 2014 Sep 15.
PubMed 26423811
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Pilot Study to Assess the Safety and Efficacy of Combined Administration With Pegylated Interferon-alpha2a and the Histone Deacetylase Inhibitor (HDACi) Panobinostat for Reducing the Residual Reservoir of HIV-1 Infected Cells in cART-Treated HIV-1 Positive Individuals
- ClinicalTrials.gov ID
- NCT02471430
- Acronym / sponsor ID
- ACTIVATE / U01 2015P000858
- Conditions
- HIV Infection
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Novartis, Genentech, Inc.
- Study start
- May 2016 (actual)
- Primary completion
- Aug 2022 (actual)
- Study completion
- Dec 2023 (actual)
- First posted
- 15 Jun 2015 (estimated)
- Results
- Posted 28 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a prospective, open-label, randomized, three-arm, dose-escalation exploratory pilot clinical trial involving HIV-1 infected participants treated with suppressive combination antiretroviral combination therapy (cART). The study will test whether combined treatment with the histone deacetylase inhibitor panobinostat and the immunomodulatory cytokine Interferon-alpha2a can reduce the residual reservoir of HIV-1 infected cells that persist during treatment with currently available antiretroviral drugs.
Detailed description
This study is a prospective, triple-arm, randomized, open-label, dose-escalation exploratory clinical trial involving HIV-1 infected participants treated with suppressive combination antiretroviral combination therapy (cART). The primary objective of this study is to evaluate a new strategy for reducing the residual reservoir of HIV-1 infected cells that persists despite treatment with current HIV drugs. The clinical trial is conducted in the Infectious Diseases Clinical Trials Unit (CTU) at the Massachusetts General Hospital.
The study medication includes two agents: panobinostat is an oral tablet that can reverse HIV-1 latency and awaken HIV from a "sleeping" condition during which it is protected from the human immune system. The second drug is pegylated interferon-alpha2a (IFN-alpha2a), an injectable cytokine that activates the immune system. The combined use of both agents may lead to immune-mediated elimination of HIV-1 infected cells in which viral latency has been reversed by panobinostat.
Participants will be randomized to receive a treatment course with panobinostat alone (Arm A, 4 participants total), panobinostat in combination with pegylated IFN-alpha2a (Arm B, 9 participants total), or pegylated IFN-alpha2a alone (Arm C, 4 participants total). Participants receiving panobinostat will undergo one week of treatment (15mg, dosed every second day on Monday, Wednesday, Friday), followed by three weeks off-treatment. Subcutaneous injections with pegylated IFN-alpha2a will be administered at the start of the week-long treatment course (simultaneously with the first dose of panobinostat for Arm B). ART will be continued during the entire treatment duration in all study participants.
Participants will undergo close monitoring for side effects during the entire time of study participation. The total study duration will be 2 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: PanobinostatParticipants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet. |
| Arm B | Experimental | Drug: Panobinostat, Drug: Pegylated Interferon-alpha2aParticipants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week. |
| Arm C | Experimental | Drug: Pegylated Interferon-alpha2aParticipants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Ability and willingness to provide informed consent
- HIV-1 infection prior to entry
- Receiving suppressive ART therapy for a minimum of 24 consecutive months prior to screening with no interruption of therapy (same ART regimen for at least 12 weeks prior to screening)
- Documented suppressed HIV-1 RNA (plasma HIV-1 RNA values <50 copies/ml)
- CD4 T cell count ≥ 400 cells/mm3
Key exclusion criteria (18 listed)
- HIV-1 RNA > 50 copies/mL within 24 months of screening
- Severe psychiatric disease, chronic liver disease, past or current evidence of immunologically mediated disease
- Severe retinopathy due to diabetes, hypertension, cytomegalovirus or macular degeneration
- Evidence of coronary heart disease
- History of active thyroid disease requiring medication
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 |
|---|---|---|
| PanobinostatAlso: Farydak, LBH589Panobinostat will be administered orally. | Drug | Arm A, Arm B |
| Pegylated Interferon-alpha2aAlso: PegasysPegylated Interferon-alpha2a will be administered subcutaneously in one shot. | Drug | Arm B, Arm C |
Primary outcome
Occurrence of Grade ≥ 1 Adverse Events (AEs)
Time frame: All adverse events measured from day 1 until day 28 after administration of the first dose of panobinostat and/or interferon-alpha2a was recorded.
Cumulative frequency and severity of Grade ≥ 1 adverse events, Grade ≥ 1 lab abnormalities or serious adverse events
Change in CD4 T Cell-Associated Proviral HIV-1 DNA From Baseline
Time frame: Measured through week 4 after administration of panobinostat and/or interferon-alpha2a
Operational measurement of CD4 T cells harboring genome-intact HIV-1 DNA, determined by the IPDA assay.
3 secondary outcomes
Change From Baseline in Histone H3 Acetylation in CD4 T Cells
Time frame: measured after last dose of PBT on day 4
Change From Baseline in Levels of CD4 T Cell-associated HIV-1 RNA
Time frame: measured after last dose of PBT on day 4
Change From Baseline in Frequency of Activated NKp30+ NK Cells.
Time frame: measured after last dose of PBT on day 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26423811Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, Winckelmann A, Palmer S, Dinarello C, Buzon M, Lichterfeld M, Lewin SR, Ostergaard L, Sogaard OS. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV. 2014 Oct;1(1):e13-21. doi: 10.1016/S2352-3018(14)70014-1. Epub 2014 Sep 15.
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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.
Mathias Lichterfeld, MD, PhD principal investigator
Massachusetts General Hospital
Daniel R Kuritzkes, MD principal investigator
Massachusetts General Hospital
Rajesh T Gandhi, MD principal investigator
Massachusetts General Hospital
1 site 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 Panobinostat and Pegylated Interferon-alpha2a in people with HIV Infection, run by Massachusetts General Hospital 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 18 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 28 Feb 2024. 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 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?
Yes. Results are posted in the registry (first posted 28 Feb 2024). 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?
Occurrence of Grade ≥ 1 Adverse Events (AEs) (time frame: All adverse events measured from day 1 until day 28 after administration of the first dose of panobinostat and/or interferon-alpha2a was recorded.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02471430, which also lists 1 linked publication.
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 Feb 2024.