Study to Evaluate Safety and Toxicity of Polyphenon E (EGCG) in HIV-1-Infected Individuals
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: Polyphenon E; Placebo
Intervention description: There will be 3 dose levels and for each dose level, there will be 6 subjects who will receive the study drug and 2 subjects who will be randomized to take placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding dose level will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each dose level is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
Intervention MeSH terms: Epigallocatechin gallate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV; safety; toxicity; pharmacokinetics; Polyphenon E; EGCG; green tea; CD4; viral load

Summary:

      The purpose of this study is to determine the safety, toxicity, dosing, and antiviral effects
      of epigallocatechin gallate (EGCG) in capsule form (Polyphenon® E), administered orally twice
      daily at three different doses in HIV-1-infected clinically stable, treatment-naïve and
      treatment-experienced adults not on concomitant antiretroviral (ARV) therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-infected individual as having at least two of the following in any combination
             obtained from 2 different samples: Positive HIV rapid test or ELISA and Western Blot;
             HIV RNA PCR>10,000 copies/ml; positive HIV DNA PCR; neutralizable HIV p 24 antigen

          -  Asymptomatic HIV-1 infected individuals who are either antiretroviral-naive or
             treatment-experienced. Subjects must have not been on ARV treatment for at least 12
             weeks prior to enrollment and not have plans to start ARV treatment within 8 weeks of
             study initiation.

          -  Male or female 18 to 65 years of age. Males must use barrier methods of contraception
             Females must be willing to abide by protocol specified methods to avoid becoming
             pregnant. Women of childbearing potential must use an adequate form of birth control
             determined by the investigator (e.g., oral contraceptives, double-barrier methods,
             hormonal injectable or implanted contraceptives, tubal ligation, or vasectomy).

          -  HIV-1 RNA >1,000 copies/mL at Screening.

          -  In the opinion of the investigator, subject has a stable CD4+ T lymphocyte count while
             off ARV and 250 cells/mm3 at Screening.

          -  Participants should have no clinically significant findings on screening evaluations
             (clinical, laboratory, or EKG).

          -  Be able to comprehend and willing to sign an ICF.

          -  Be able to comply with the protocol requirements.

          -  Have life expectancy > 6 months.

          -  Laboratory values obtained during screening must be within normal limits or meet the
             following requirements (Safety Labs):

          -  ANC 1000/mm3

          -  Hemoglobin 9.0 g/dL

          -  Glucose (nonfasting) <116 mg/dL

          -  Bilirubin 1.5 x upper limit of normal (ULN)

          -  Liver function tests (AST & ALT) 1.25 x ULN at screening and baseline

          -  GGT < 5.0 x ULN

          -  Negative hepatitis panel obtained less than or equal to 6 months prior to Study Entry

          -  Creatinine 1.3 x ULN

          -  Creatine phosphokinase (CPK) 5 x ULN unless further evaluation determines it to be due
             to exercise

          -  Urine protein 2+

          -  Prothrombin time (PT)1.25 x ULN

          -  Lipase 1.2 x ULN

        Exclusion Criteria:

          -  Current or recent (<3 months) history of opportunistic infection that,

          -  Acute illness within 1 week of the baseline visit.

          -  Participant is not able to comply with the dosing schedule and protocol evaluations.

          -  Participant is anticipated to begin ARV treatment during participation in the study.

          -  Pregnancy, breastfeeding or postpartum (less than 3 months).

          -  Diagnosis of diabetes.

          -  Any condition which could compromise participant safety or adherence to the protocol.

          -  Documented positive test for hepatitis B surface antigen, hepatitis B surface antibody
             (with the exception of participants who received hepatitis B vaccination and have
             hepatitis B surface antibody), hepatitis B core antibody, and hepatitis C antibody.

          -  Any grade 3 or 4 laboratory abnormality noted at screening according to the DAIDS
             grading scale (Appendix A), except for the following:

          -  Grade 3 or 4 triglyceride elevations.

          -  Grade 3 cholesterol elevation.

          -  Grade 3 non-fasting glucose elevation.

          -  Participant has a malabsorption syndrome possibly affecting drug absorption (e.g.
             Crohn's disease or chronic pancreatitis).

          -  Participant has received an HIV prophylactic or therapeutic vaccination within 6
             months prior to the first dose of study medication.

          -  Investigational therapy within 30 days prior to the Baseline visit.

          -  Radiation therapy or systemic cytotoxic chemotherapeutic agents within 12 weeks prior
             to the baseline visit or have not recovered from side effects from such therapy prior
             to the first dose of study medication.

          -  Positive urine screen for drugs of abuse at Screening, unless the investigator deems
             that the result is associated with a prescribed medication or inhaled use of THC.

          -  Inability to avoid all tea/tea products (including herbal, caffeinated, decaffeinated,
             iced tea), apples, chocolate, broad beans (fava beans), plums, prunes, cherries, fruit
             juices containing apples, cherries, or plums, dietary supplements, and herbal products
             for 1 week prior to the baseline visit and for the duration of the study.

          -  Inability to limit caffeine intake to not exceed 12 oz. of caffeinated beverage per
             day (if espresso, no more than 1 oz. or 1 shot) beginning 2 days prior and for the
             duration of the study.

          -  Prior exposure to TNX-355 (an investigational anti-HIV agent that binds to the CD4+ T
             lymphocyte surface).

          -  Participant has used proton pump inhibitors starting 14 days before Study Day 1 and is
             unable to avoid taking proton pump inhibitors for the duration of the study.

          -  Participant has used H2 blockers starting 24 hours before Study Day 1 and is unable to
             avoid taking H2 blockers for the duration of the study.