Safety/Effectiveness of Oral Chemokine Coreceptor 5 (CCR5) Antagonist INCB009471 in R5-tropic HIV Infected Patients

Study Overview
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Brief Summary
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This study will evaluate the safety, pharmacokinetics and efficacy of the CCR5 antagonist INCB009471 in HIV-1 infected patients who are antiretroviral therapy naïve, or who are not currently on a HAART regimen and have not received any antiretroviral agents for 3 months prior to the Screening visit. Subjects will receive study medication (INCB009471) admnistered orally or placebo once daily with food for 14 days. Clinical safety laboratories, 12-lead electrocardiograms, physical examinations and virologic assessments, including viral load, viral tropism and CD4+ cell count determinations will be performed at the Screening visit and at regularly scheduled visits throughout the study. A blood sample will also be obtained and stored to potentially determine the genotype of the CCR5 receptor. The primary objectives are: Assess the safety and tolerability of 3 doses of INCB009471 or placebo when administered orally, once daily, as monotherapy for 14 days; Determine the pharmacokinetics of 3 doses of INCB009471 or placebo when administered orally, once daily, as monotherapy for 14 days; Evaluate the anti-retroviral activity of 3 doses of INCB009471 or placebo when administered orally, once daily, as monotherapy for 14 days

Official Title
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A Randomized, Double-blind, Placebo-controlled Study Exploring the Safety, Tolerability, PK & Virological Effect of Once Daily Oral Dosing of INCB009471 as Monotherapy for 14 Days in ARV-naïve/Limited ARV-experienced, HIV-1 Infected Pts.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: INCB009471
* Drug: INCB009471
* Drug: Placebo comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asymptomatic HIV-1 infected individuals that are treatmen naïve (ie less than 2 weeks prior ARV exposure) or treatment experienced subjects who are not currently on HAART and have not received any ARVs for 3 months prior to Screening. Males between 18 years and 65 years of age, utilizing adequate contraceptive methods. Post menopausal or surgically sterile females between 18 years and 65 years of age. Women of childbearing potential, utilizing adequate contraceptive methods. CD4-lymphocyte count >350 cells/mm3 HIV-1 RNA copies/ml > 10,000. HIV-1 is CCR5 tropic virus only. CCR5 antagonist treatment naive. BMI > 16 to < 32 kg/m2. Have no clinically significant findings on screening evaluations, which in the opinion of the Investigator would interfere with the subject's ability to comply with the protocol. Able to comprehend and willing to sign an Informed Consent Form. Exclusion Criteria: Current or recent (<30 days) opportunistic infection. Presence of CXCR4- or dual-tropic HIV-1 virus at Screening or Baseline assessments. Subjects with chronic renal insufficiency Personal history of cardiac diseases. History or presence of an abnormal ECG. History of unstable ischemic heart disease or uncontrolled hypertension. History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin. Subjects who have received radiation therapy or cytotoxic chemotherapeutic agents and have not recovered from side effects. Current treatment or treatment within 30 days or 5 half-lives with another investigational medication or current enrollment in another investigational drug protocol. Subjects with unstable medical condition (s), which , in the opinion of the Investigator would compromise their participation in the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A - INCB009471 100mg IR<br>INCB009471, 100 mg IR orally once daily | Drug: INCB009471<br>* 100mg SR (sustained release) orally once daily<br>|
| Experimental: Treatment B - INCB009471 300mg SR<br>INCB009471, 300 mg SR orally once daily | Drug: INCB009471<br>* 300mg SR (sustained release) orally once daily<br>|
| Placebo Comparator: Treatment C - Placebo<br>Placebo matching INCB009471 | Drug: Placebo comparator<br>* Orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability will be assessed by monitoring adverse experiences. |  | Baseline, every 1-7 days following the initiation of treatment through Day 28 and then at Day 42 or the early study termination visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The virological response to INCB009471 as monotherapy will be assessed by measuring HIV-1 RNA levels by the Roche Amplicor HIV-1 Monitor® Test, v1.5 - Quantitative. |  | Baseline, Days 4, 7, 10, 14, 16, 20 and 28 or the early termination study visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-infection, viral load, CCR5, viral tropism, HIV-1 infection, Treatment Naive