HIVPhase 1/2GoldrakeNCT02176135
Oral Auranofin for Reduction of Latent Viral Reservoir in Patients With HIV Infection
A Phase 1/2 study testing Auranofin in people with HIV, run by Vaccine and Gene Therapy Institute, Florida at 1 site in United States.
Trial summary
The main purpose of the study is to evaluate the safety of oral auranofin, a gold compound, in patients with HIV infection whose viral load has been suppressed by antiretroviral therapy for no less than 3 years and have a CD4+ cell count over 500 cells/uL Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- HIV
- What is being tested?
- Auranofin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Start not givento Jan 2017
- 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Participant is willing and able to give informed consent for participation in the study.
- Male or female, between 18 and 55 years of age.
- Stable dose of ART (defined as at least 2 nucleoside/nucleotide reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor, integrase inhibitor, or a protease inhibitor) for at least 2 years from study consent and with no modifications expected during the study.
- HIV plasma viral load <50 copies/ml for at least 3 years with several measurements per year and most recent viral load within 3 months of screening.8
- No previous failure of ART, understood as a rebound in viral load that can be detected after having reached undetectable levels. Low-grade increases (<200 copies of HIV RNA/mL) and transitory increases (blips) resolved without modifying ART are acceptable.
- Did not experience AIDS defining event
- Two CD4+ T cell counts greater than 500 cell/µl in the six months prior to screening
- Able (in the Investigators' opinion) and willing to comply with all study requirements.
Who cannot join
- Contraindication to auranofin therapy, including congestive heart failure, renal dysfunction, history of blood dyscrasias; History of gold induced disorders (e.g. necrotising enterocolitis, pulmonary fibrosis, exfoliative dermatitis, bone marrow aplasia or other sever hematologic disorders), porphyria; History of severe allergic or anaphylactic reactions or hypersensitivity to auranofin or other gold compounds.
- Treatment with nucleoside/nucleotide analogs with higher risk of mitochondrial toxicity: zidovudine (ZDV), Stavudine (d4T), didanosine (ddI), di-deoxy-cytidine (ddC) or abacavir (ABC).
- Presence of clinically significant skin/mucosal disease such as hives or dermatitis, pruritus or rash, eczema, stomatitis or conjunctivitis
- Significant acute medical illness in the past 4 weeks
- Inflammatory bowel disease, Crohn's disease or ulcerative colitis
- Current or recent (i.e. within 2 weeks) gastrointestinal disease or GI disturbances, including vomiting, abdominal pain, diarrhea, which may impact the absorption of the investigational drug
Show all 21Show fewer
- History of gastrointestinal surgery that could impact upon the absorption of Auranofin
- Scheduled elective surgery or other procedures requiring general anesthesia during the study
- Participant has the following laboratory values within 2 weeks before starting the investigational drug (laboratory tests may be repeated, as clinically indicated, to obtain acceptable values before failure at screening is concluded)
- Known hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood
- Receipt of immunomodulating therapy, EPO or G-CSF, immunization or systemic chemotherapeutic agents within 12 weeks prior to study entry
- Anticipated requirement for treatment with drugs that may interfere with auranofin as outlined in Appendix 7.
- Receipt of RBC or platelet transfusion or receipt of cell product within 24 weeks prior to study entry
- Insulin dependent diabetes
- Systemic Lupus Erythematosus (SLE)
- Current or history of seizure disorder
- Previous diagnosis of lymphoma or other HIV related cancers.
- Any other significant disease or disorder (including psychiatric disorders) which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
- 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 24 weeks after study treatment
- Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the entire study period, including at least 4 weeks before, 4 weeks after study treatment, and when plasma HIV-RNA is detectable using standard assays
- Subjects who have participated in another research study involving an investigational product in the past 12 weeks.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Miami - AIDS Clinical Research Unit
Miami, Florida, 33136
About this study
Official title: A Dose Escalation Phase I Study to Evaluate the Safety and Tolerability of Oral Auranofin Therapy in HIV-infected Subjects Receiving Suppressive Antiretroviral Therapy
The main purpose of the study is to evaluate the safety of oral auranofin, a gold compound, in patients with HIV infection whose viral load has been suppressed by antiretroviral therapy for no less than 3 years and have a CD4+ cell count over 500 cells/uL
Read the detailed description
The investigators proposed a novel approach in order to reduce the HIV viral reservoir. This approach exploits the effects of auranofin, a gold based compound which has been used in the treatment of rheumatoid arthritis. Auranofin induces partially selective apoptosis and differentiation towards short-lived phenotypes of the T lymphocyte memory subsets that encompass the main viral reservoir in patients. The hypothesis is that the targeted memory cells would either die or decrease their persistence in the body, with the associated latent viral reservoir being reduced.
The study will be conducted in two phases: A sequential dose-escalation phase to evaluate two doses of auranofin, followed by an expansion at the maximum tolerated dose (MTD). A total of 20 patients are to be treated at the MTD. Auranofin treatment is administered for 12 weeks.
Safety and tolerability will be evaluated by repeated laboratory panel and physcial examination during the 12 weeks of auranofin therapy and 8 for weeks thereafter. The latent reservoir will be measured by assessment of the inegrated viral DNA in CD4+ cells in the circulating blood and in gut biopsies.
- Conditions
- HIV
- Being tested
- Auranofin
- Keywords
- HIV, HAART suppressed, Auranofin, HIV latent reservoir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AuranofinDrug
Also called Ridaura
3 mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | Auranofin 3 to 6 mg/day oral administration for 12 weeks Receives: Drug: Auranofin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
Adverse event frequency and severity per NIAID ACTG grading tables
Measured: 12 weeks treatment and 8 weeks post-therapy
Secondary outcomes (1)
Change from baseline in measures of the HIV latent reservoir during auranofin therapy
The size of the latent reservoir will be measured by the frequency of CD4+ T cells harboring total and integrated HIV DNA and by the frequency of CD4+ T-cells cells harboring inducible HIV multiply-spliced RNA upon maximal stimulation (expressed as infected cells per million CD4+ T cells).
Measured: 12 weeks therapy and 8 weeks post-therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2014 (estimated)
- Primary completionJan 2016 (estimated)
- Study completionJan 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vaccine and Gene Therapy Institute, Florida
- Sponsor type
- University, hospital or other
- Collaborators
- University of Miami
- Responsible party
- Sponsor
- Investigators
- Patrick D Yeramian, MD, Study director, Vaccine and Gene Therapy Institute, Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02176135
- Sponsor's protocol ID
- AUR-001
- Acronym
- Goldrake
- Status last verified
- Feb 2015
- First submitted
- 24 Jun 2014
- Last updated
- 26 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Phase I Study to Evaluate the Safety and Tolerability of Oral Auranofin Therapy in HIV-infected Subjects Receiving Suppressive Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT02176135
- Acronym / sponsor ID
- Goldrake / AUR-001
- Conditions
- HIV
- Keywords
- HIV, HAART suppressed, Auranofin, HIV latent reservoir
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vaccine and Gene Therapy Institute, FloridaUniversity, hospital or other
- Collaborators
- University of Miami
- Primary completion
- Jan 2016 (estimated)
- Study completion
- Jan 2017 (estimated)
- First posted
- 26 Jun 2014 (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 main purpose of the study is to evaluate the safety of oral auranofin, a gold compound, in patients with HIV infection whose viral load has been suppressed by antiretroviral therapy for no less than 3 years and have a CD4+ cell count over 500 cells/uL
Detailed description
The investigators proposed a novel approach in order to reduce the HIV viral reservoir. This approach exploits the effects of auranofin, a gold based compound which has been used in the treatment of rheumatoid arthritis. Auranofin induces partially selective apoptosis and differentiation towards short-lived phenotypes of the T lymphocyte memory subsets that encompass the main viral reservoir in patients. The hypothesis is that the targeted memory cells would either die or decrease their persistence in the body, with the associated latent viral reservoir being reduced.
The study will be conducted in two phases: A sequential dose-escalation phase to evaluate two doses of auranofin, followed by an expansion at the maximum tolerated dose (MTD). A total of 20 patients are to be treated at the MTD. Auranofin treatment is administered for 12 weeks.
Safety and tolerability will be evaluated by repeated laboratory panel and physcial examination during the 12 weeks of auranofin therapy and 8 for weeks thereafter. The latent reservoir will be measured by assessment of the inegrated viral DNA in CD4+ cells in the circulating blood and in gut biopsies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: AuranofinAuranofin 3 to 6 mg/day oral administration for 12 weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Participant is willing and able to give informed consent for participation in the study.
- Male or female, between 18 and 55 years of age.
- Stable dose of ART (defined as at least 2 nucleoside/nucleotide reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor, integrase inhibitor, or a protease inhibitor) for at least 2 years from study consent and with no modifications expected during the study.
- HIV plasma viral load <50 copies/ml for at least 3 years with several measurements per year and most recent viral load within 3 months of screening.8
- No previous failure of ART, understood as a rebound in viral load that can be detected after having reached undetectable levels. Low-grade increases (<200 copies of HIV RNA/mL) and transitory increases (blips) resolved without modifying ART are acceptable.
Key exclusion criteria (21 listed)
- Contraindication to auranofin therapy, including congestive heart failure, renal dysfunction, history of blood dyscrasias; History of gold induced disorders (e.g. necrotising enterocolitis, pulmonary fibrosis, exfoliative dermatitis, bone marrow aplasia or other sever hematologic disorders), porphyria; History of severe allergic or anaphylactic reactions or hypersensitivity to auranofin or other gold compounds.
- Treatment with nucleoside/nucleotide analogs with higher risk of mitochondrial toxicity: zidovudine (ZDV), Stavudine (d4T), didanosine (ddI), di-deoxy-cytidine (ddC) or abacavir (ABC).
- Presence of clinically significant skin/mucosal disease such as hives or dermatitis, pruritus or rash, eczema, stomatitis or conjunctivitis
- Significant acute medical illness in the past 4 weeks
- Inflammatory bowel disease, Crohn's disease or ulcerative colitis
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 |
|---|---|---|
| AuranofinAlso: Ridaura3 mg tablets | Drug | Dose escalation |
Primary outcome
Safety and Tolerability
Time frame: 12 weeks treatment and 8 weeks post-therapy
Adverse event frequency and severity per NIAID ACTG grading tables
1 secondary outcome
Change from baseline in measures of the HIV latent reservoir during auranofin therapy
Time frame: 12 weeks therapy and 8 weeks post-therapy
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 26 Feb 2015.
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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.
Patrick D Yeramian, MD study director
Vaccine and Gene Therapy Institute, Florida
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 Auranofin in people with HIV, run by Vaccine and Gene Therapy Institute, Florida 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 8 inclusion and 21 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 26 Feb 2015. 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?
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.
What does the primary outcome measure?
Safety and Tolerability (time frame: 12 weeks treatment and 8 weeks post-therapy). 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 26 Feb 2015.