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Oral Auranofin for Reduction of Latent Viral Reservoir in Patients With HIV Infection

Information source: Vaccine and Gene Therapy Institute, Florida
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV

Intervention: Auranofin (Drug)

Phase: Phase 1/Phase 2

Status: Withdrawn

Sponsored by: Vaccine and Gene Therapy Institute, Florida

Official(s) and/or principal investigator(s):
Patrick D Yeramian, MD, Study Director, Affiliation: Vaccine and Gene Therapy Institute, Florida

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

Clinical Details

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

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Safety and Tolerability

Secondary outcome: Change from baseline in measures of the HIV latent reservoir during auranofin therapy

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.

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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. Exclusion Criteria:

- 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

- 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.

Locations and Contacts

University of Miami - AIDS Clinical Research Unit, Miami, Florida 33136, United States
Additional Information


Last updated: February 25, 2015

Page last updated: August 23, 2015

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