Clinical trial NCT00393120: Safety/Effectiveness of Oral Chemokine Coreceptor 5 (CCR5) Antagonist INCB009471 in R5-tropic HIV Infected Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV-infection
viral load
CCR5
viral tropism
HIV-1 infection
Treatment Naive
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2006-10-26
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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:

1. Assess the safety and tolerability of 3 doses of INCB009471 or placebo when administered orally, once daily, as monotherapy for 14 days;
2. Determine the pharmacokinetics of 3 doses of INCB009471 or placebo when administered orally, once daily, as monotherapy for 14 days;
3. Evaluate the anti-retroviral activity of 3 doses of INCB009471 or placebo when administered orally, once daily, as monotherapy for 14 days


Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability will be assessed by monitoring adverse experiences.
timeFrame: 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 outcomes:
measure: 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.
timeFrame: Baseline, Days 4, 7, 10, 14, 16, 20 and 28 or the early termination study visit.
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Orlando
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Annandale
country: United States
state: Virginia
Study officials:
affiliation: Incyte Corporation
name: Richard Levy, MD
role: STUDY_DIRECTOR
References: