A Phase Ib Randomized, Double-blind, Placebo-controlled, Ascending Sequential Dose, Adaptive Design Study to Evaluate the Safety, Antiretroviral Activity, and Pharmacokinetics of Intravenous Deferiprone in Treatment-Naïve HIV-Positive Subjects
Overview
- Phase
- Phase 1
- Intervention
- Intravenous deferiprone
- Conditions
- Asymptomatic HIV Infection
- Sponsor
- ApoPharma
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Number of subjects with adverse events
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This study will evaluate the safety, tolerability, antiretroviral activity, pharmacokinetics, and pharmacodynamics of an intravenous formulation of deferiprone in HIV-infected subjects.
Detailed Description
This is a double-blind, placebo-controlled, randomized trial in 30 asymptomatic HIV-positive adults. There are two sequential cohorts, in which subjects will receive either one of 2 doses of deferiprone or placebo twice daily.
Investigators
Eligibility Criteria
Inclusion Criteria
- •HIV-1 positive
- •HIV treatment-naïve: no previous treatment with a combination anti-retroviral therapy (cART) or highly active anti-retroviral therapy (HAART) regimen
- •HIV-1 RNA \> 10,000 copies/mL
- •ALT or AST ≤ 2.0 x upper limit of normal range, and bilirubin within normal range
- •Body mass index (BMI) of 18.5 to 30.0 kg/m\^2
- •Absolute neutrophil count at baseline of ≥1.0 x 10\^9/L (black African population only) or ≥1.5 x 10\^9/L (all other races)
Exclusion Criteria
- •Evidence of AIDS-associated illness, excluding superficial candidiasis
- •CD4+ T-cell count of \< 350/mm\^3
- •Positive for active or latent tuberculosis, as determined by the QuantiFERON®-TB Gold test
- •Active, serious infections (other than HIV-1 infection) within the 30 days prior to screening
- •Positive for hepatitis B surface antigen (HBsAg) and/or hepatitis virus C (HCV) antibodies
- •History or presence of malignancy
- •A serious, unstable chronic illness during the past 3 months before screening
- •A serious, unresolved acute illness at screening
Arms & Interventions
Intravenous deferiprone, 1.5 g
Subjects in this arm will receive an infusion of intravenous deferiprone at a dose of 1.5 g, twice-daily
Intervention: Intravenous deferiprone
Intravenous deferiprone, 2 g
Subjects in this arm will receive an infusion of intravenous deferiprone at a dose of 2 g, twice-daily
Intervention: Intravenous deferiprone
Placebo
Subjects in this arm will receive an infusion of placebo twice-daily for 10 days, at a volume equivalent to that of the active product in the respective cohort
Intervention: Placebo
Outcomes
Primary Outcomes
Number of subjects with adverse events
Time Frame: Day 1 to Day 56
Change from baseline in level of HIV DNA in peripheral blood mononucleated cells
Time Frame: Day 1 to Day 56
Proportion of subjects withdrawn due to the need for rescue medication
Time Frame: Day 1 to Day 56
Change from baseline in HIV viral load
Time Frame: Day 1 to Day 56
Change from baseline in CD4+ T-cell count
Time Frame: Day 1 to Day 56
Secondary Outcomes
- The pharmacokinetics parameters of Cmax, Tmax, and AUC0-∞, and T1/2 for deferiprone will be determined pre-dose and at specified time points post-dose(10-hour interval)