Evaluation of the Safety, Efficacy, and Pharmacokinetics of Intravenous Deferiprone in HIV-Positive Subjects

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, antiretroviral activity, pharmacokinetics, and pharmacodynamics of an intravenous formulation of deferiprone in HIV-infected subjects.

Detailed Description
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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.

Official Title
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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

Conditions
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Asymptomatic HIV Infection

Intervention / Treatment
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* Drug: Intravenous deferiprone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous deferiprone, 1.5 g<br>Subjects in this arm will receive an infusion of intravenous deferiprone at a dose of 1.5 g, twice-daily | Drug: Intravenous deferiprone<br>* In Cohort 1, the subjects who were randomized to get active product will receive deferiprone at a dose of 1.5 g per infusion, and if there are no significant safety concerns, the subjects in Cohort 2 who were randomized to get active product will receive it a a dose of 2 g per infusion.<br>* Other names: Deferiprone injection, solution;|
| Experimental: Intravenous deferiprone, 2 g<br>Subjects in this arm will receive an infusion of intravenous deferiprone at a dose of 2 g, twice-daily | Drug: Intravenous deferiprone<br>* In Cohort 1, the subjects who were randomized to get active product will receive deferiprone at a dose of 1.5 g per infusion, and if there are no significant safety concerns, the subjects in Cohort 2 who were randomized to get active product will receive it a a dose of 2 g per infusion.<br>* Other names: Deferiprone injection, solution;|
| Placebo Comparator: Placebo<br>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 | Drug: Placebo<br>* In both cohorts, the subjects who were randomized to get placebo will receive an infusion of placebo solution that is equal in volume to that of the active product.<br>* Other names: Normal saline solution (0.9% w/v NaCl);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HIV viral load |  | Day 1 to Day 56 | 
| Change from baseline in CD4+ T-cell count |  | Day 1 to Day 56 | 
| Change from baseline in level of HIV DNA in peripheral blood mononucleated cells |  | Day 1 to Day 56 | 
| Proportion of subjects withdrawn due to the need for rescue medication |  | Day 1 to Day 56 | 
| Number of subjects with adverse events |  | Day 1 to Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, HIV infection, antiretroviral drugs, deferiprone