HIV PositivePhase 2NCT01365065

Safety and Effect on HIV Transcription of Vorinostat in Patients Receiving Suppressive Combination Anti-retroviral Therapy

A Phase 2 study testing Vorinostat in people with HIV Positive, run by Bayside Health at 1 site in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Trial summary

The objective of the study is to assess the safety and ability of vorinostat, a drug currently licensed for the treatment of a type of lymphoma, to 'turn on' dormant HIV infected CD4 T-cells. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: HIV Positive
What is being tested?: Vorinostat
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteAustralia
Study dates: May 2011to Jan 2018
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 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

HIV -1 infected adults
HIV-1 plasma RNA <50 copies/ml for at least 3 years with at least 2 viral load measures per year, and most recent viral load within 3 months of screening. Episodes of a single HIV plasma RNA 50-199 copies/ml will not exclude participation if the subsequent HIV plasma RNA was <50 copies/ml.
Receiving combination antiretroviral therapy (at least 3 agents)
In the last 6 months have two CD4 cell count greater than 500 cell/µl
Documented subtype B HIV infection
Detectable HIV RNA on stored specimen
Able to give informed consent

Who cannot join

Any significant acute medical illness in the past 8 weeks.
Any evidence of an active AIDS-defining opportunistic infection.
Current or recent gastrointestinal disease that may impact the absorption of study drug.
Any gastrointestinal surgery that could impact upon the absorption of study drug.
Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy .
Moderate to severe hepatic impairment

Show all 17Show fewer

Hepatic transaminases (AST or ALT) > 3 x upper limit of normal (ULN)
Hepatitis B infection as indicated by the presence of Hepatitis B surface antigen or detectable DNA levels in blood.
A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes (e.g. heart failure).
History of malignancy or transplantation, including skin cancers or Kaposi sarcoma
History of diabetes mellitus
Use of an HIV protease inhibitor.
Receipt of immunomodulating agents, immunization or systemic chemotherapeutic agents within 28 days prior to screening.
Use of an agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening.
Receipt of sodium valproate or other HDAC inhibitor at any time.
Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period and for at least 4 weeks before and 4 weeks after the study.
Males who are unwilling or unable to use barrier contraception during vaginal intercourse from the time of enrollment and for 12 weeks after participation in the study are also excluded.

Trial locations and contacts

1 site in 1 country.

Australia1 site

The Alfred Hospital - Infectious Diseases Unit
Melbourne, Victoria, 3004

Other trials in Australia

About this study

Official title: A Pilot Study to Assess the Safety and Effect on HIV Transcription of Vorinostat in Patients Receiving Suppressive Combination Anti-retroviral Therapy

The objective of the study is to assess the safety and ability of vorinostat, a drug currently licensed for the treatment of a type of lymphoma, to 'turn on' dormant HIV infected CD4 T-cells.

Read the detailed description

Treatment of HIV infection with combination antiretroviral therapy (cART) has led to significant improvements in the life expectancy and quality of life of people living with HIV. Nevertheless, life expectancy is significantly lower than uninfected individuals and cART leads to several long term side effects. cART alone is not able to cure HIV infection due to persistence of HIV infection in dormant cells. One potential strategy to eradicate HIV infection is to 'wake up' these dormant infected cells by 'turning on' the cell. The small number of cells that are dormant and infected would start to produce virus and die, but infection of other cells would be prevented by cART. Ultimately this could lead to eradication of dormant infected cells and a potential cure for HIV.

This study is a pilot study in 20 individuals recruited at the Alfred Hospital only.

The hypotheses is that vorinostat will induce HIV transcription in CD4 T-cells with latent HIV infection, it is safe and well tolerated in patients receiving effective cART and will induce histone acetylation in vivo in patients with HIV infection.

The study will run over 12 weeks, involving 9 study visits for the participant. Eligible patients must be between 18 to 60 years of age with confirmed HIV infection, and receiving successful cART as indicated by 'suppressed' HIV virus in blood (plasma HIV RNA <50 copies/ml) for at least 3 years and a strong immune system (two CD4 counts greater than 500 cell/µl in the last 6 months).

Patients will be reviewed at screening and days 1 (three time points), 2, 7, 14, 21, 28 and 84 (week 12). They will have blood tests for HIV viral load assessment, CD4 cell counts, biochemistry, hematology and storage samples. An electrocardiogram of the heart (ECG) will be taken at screening, day 7 and 14.

As part of this study levels of HIV in blood and in white blood cells and the degree to which cells are 'turned on' (histone (H3) acetylation) will be measured at 3 time points on day 1, then once on days 2, 7, 14, 21 and 28. The level of one component of cART will be measured at day 1 and 14. At baseline and day 14 a sigmoidoscopy if performed for the collection of rectal biopsies.

The safety and how well vorinostat is tolerated will be determined based on physical exams, laboratory tests and questions about any problems patients may have experienced during the study. This study has an Independent Safety Monitoring Committee who in addition to evaluating the overall safety of patients will be responsible for assessing safety of the first patient enrolled prior to any recommendation to continue the study.

Conditions: HIV Positive
Being tested: Vorinostat
Medical subject headings: HIV Seropositivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VorinostatDrug
Vorinostat 400mg (4 x 100mg) orally daily for 14 days

Study groups in NCT01365065
Study group	Role	What they receive
Vorinostat	Experimental	Vorinostat 400mg ( 4 X 100mg ) orally daily for 14 days Receives: Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

To evaluate the effect of vorinostat on HIV transcription in CD4 T-cells.
The primary (efficacy) endpoint of this study is to evaluate the effect of vorinostat on HIV transcription from latently infected CD4+ T-cells as measured by HIV unspliced RNA in CD4+ T-cells.
Measured: Day 1 (before drug, 2 and 8 hours after first dose), Day 2, 7, 14, 21 and 28

Secondary outcomes (1)

1. To evaluate the safety and tolerability of vorinostat in patients receiving effective combination antiretroviral therapy (cART
1. Plasma HIV RNA (standard assay)
2. Adverse events and dose-limiting toxicity
3. CD4 T-cell count
4. Antiretroviral plasma trough concentrations will be measured before and after 14 days of treatment with vorinostat.
Measured: Screening, Day 1, 7, 14,21, and 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2011Jan 2018

First posted3 Jun 2011 (estimated)
Study startMay 2011
Primary completionDec 2011
Study completionJan 2018 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for HIV PositiveStudies 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: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01365065
Sponsor's protocol ID: U1111-1121-9077
Status last verified: Apr 2017
First submitted: 1 Jun 2011
Last updated: 25 Apr 2017
Results posted: No
Data monitoring committee: Yes

Publications

Elliott JH, Wightman F, Solomon A, Ghneim K, Ahlers J, Cameron MJ, Smith MZ, Spelman T, McMahon J, Velayudham P, Brown G, Roney J, Watson J, Prince MH, Hoy JF, Chomont N, Fromentin R, Procopio FA, Zeidan J, Palmer S, Odevall L, Johnstone RW, Martin BP, Sinclair E, Deeks SG, Hazuda DJ, Cameron PU, Sekaly RP, Lewin SR. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 2014 Nov 13;10(10):e1004473. doi: 10.1371/journal.ppat.1004473. eCollection 2014 Oct.
PubMed 25393648
Mota TM, Rasmussen TA, Rhodes A, Tennakoon S, Dantanarayana A, Wightman F, Hagenauer M, Roney J, Spelman T, Purcell DFJ, McMahon J, Hoy JF, Prince HM, Elliott JH, Lewin SR. No adverse safety or virological changes 2 years following vorinostat in HIV-infected individuals on antiretroviral therapy. AIDS. 2017 May 15;31(8):1137-1141. doi: 10.1097/QAD.0000000000001442.
PubMed 28301423

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 25 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study to Assess the Safety and Effect on HIV Transcription of Vorinostat in Patients Receiving Suppressive Combination Anti-retroviral Therapy
ClinicalTrials.gov ID: NCT01365065
Acronym / sponsor ID: U1111-1121-9077
Conditions: HIV Positive
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 20 participants (actual)
Lead sponsor: Bayside HealthOther government
Collaborators: Merck Sharp & Dohme LLC
Study start: May 2011 (actual)
Primary completion: Dec 2011 (actual)
Study completion: Jan 2018 (estimated)
First posted: 3 Jun 2011 (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 objective of the study is to assess the safety and ability of vorinostat, a drug currently licensed for the treatment of a type of lymphoma, to 'turn on' dormant HIV infected CD4 T-cells.

Detailed description

This study is a pilot study in 20 individuals recruited at the Alfred Hospital only.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Vorinostat	Experimental	Drug: VorinostatVorinostat 400mg ( 4 X 100mg ) orally daily for 14 days

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

HIV -1 infected adults
HIV-1 plasma RNA <50 copies/ml for at least 3 years with at least 2 viral load measures per year, and most recent viral load within 3 months of screening. Episodes of a single HIV plasma RNA 50-199 copies/ml will not exclude participation if the subsequent HIV plasma RNA was <50 copies/ml.
Receiving combination antiretroviral therapy (at least 3 agents)
In the last 6 months have two CD4 cell count greater than 500 cell/µl
Documented subtype B HIV infection

Key exclusion criteria (17 listed)

Any significant acute medical illness in the past 8 weeks.
Any evidence of an active AIDS-defining opportunistic infection.
Current or recent gastrointestinal disease that may impact the absorption of study drug.
Any gastrointestinal surgery that could impact upon the absorption of study drug.
Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study 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
VorinostatVorinostat 400mg (4 x 100mg) orally daily for 14 days	Drug	Vorinostat

Primary outcome

To evaluate the effect of vorinostat on HIV transcription in CD4 T-cells.
Time frame: Day 1 (before drug, 2 and 8 hours after first dose), Day 2, 7, 14, 21 and 28
The primary (efficacy) endpoint of this study is to evaluate the effect of vorinostat on HIV transcription from latently infected CD4+ T-cells as measured by HIV unspliced RNA in CD4+ T-cells.

1 secondary outcome

1. To evaluate the safety and tolerability of vorinostat in patients receiving effective combination antiretroviral therapy (cART
Time frame: Screening, Day 1, 7, 14,21, and 28

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2017.
Results publication: PubMed 25393648Elliott JH, Wightman F, Solomon A, Ghneim K, Ahlers J, Cameron MJ, Smith MZ, Spelman T, McMahon J, Velayudham P, Brown G, Roney J, Watson J, Prince MH, Hoy JF, Chomont N, Fromentin R, Procopio FA, Zeidan J, Palmer S, Odevall L, Johnstone RW, Martin BP, Sinclair E, Deeks SG, Hazuda DJ, Cameron PU, Sekaly RP, Lewin SR. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 2014 Nov 13;10(10):e1004473. doi: 10.1371/journal.ppat.1004473. eCollection 2014 Oct.
Results publication: PubMed 28301423Mota TM, Rasmussen TA, Rhodes A, Tennakoon S, Dantanarayana A, Wightman F, Hagenauer M, Roney J, Spelman T, Purcell DFJ, McMahon J, Hoy JF, Prince HM, Elliott JH, Lewin SR. No adverse safety or virological changes 2 years following vorinostat in HIV-infected individuals on antiretroviral therapy. AIDS. 2017 May 15;31(8):1137-1141. doi: 10.1097/QAD.0000000000001442.

Related trials for HIV Positive

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Pregnant HIV Positive Women
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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.

The record lists no contact. Use the official record to reach the sponsor.

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 Vorinostat in people with HIV Positive, run by Bayside Health at 1 site in Australia.

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 17 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: status not confirmed, as of the sponsor's last update on 25 Apr 2017. 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 Australia. 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?

Results are not available in the source record.

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?

To evaluate the effect of vorinostat on HIV transcription in CD4 T-cells. (time frame: Day 1 (before drug, 2 and 8 hours after first dose), Day 2, 7, 14, 21 and 28). 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 NCT01365065, which also lists 2 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 25 Apr 2017; AzTrials last refreshed its copy on 8 Nov 2026.