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

Purpose

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

Condition	Intervention	Phase
HIV Infections	Drug: INCB009471 Drug: Placebo comparator	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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.

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by Incyte Corporation:

Primary Outcome Measures:

Safety and tolerability will be assessed by monitoring adverse experiences. [ Time Frame: Baseline, every 1-7 days following the initiation of treatment through Day 28 and then at Day 42 or the early study termination visit. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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. [ Time Frame: Baseline, Days 4, 7, 10, 14, 16, 20 and 28 or the early termination study visit. ] [ Designated as safety issue: No ]

Enrollment:	45
Study Start Date:	October 2006
Study Completion Date:	September 2007
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment A - INCB009471 100mg IR INCB009471, 100 mg IR orally once daily	Drug: INCB009471 100mg SR (sustained release) orally once daily
Experimental: Treatment B - INCB009471 300mg SR INCB009471, 300 mg SR orally once daily	Drug: INCB009471 300mg SR (sustained release) orally once daily
Placebo Comparator: Treatment C - Placebo Placebo matching INCB009471	Drug: Placebo comparator Orally once daily

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00393120

Locations

United States, California

Los Angeles, California, United States, 90069
United States, District of Columbia

Washington, District of Columbia, United States, 20007
United States, Florida

Orlando, Florida, United States, 32803

Vero Beach, Florida, United States, 32960
United States, Massachusetts

Boston, Massachusetts, United States, 02130
United States, Virginia

Annandale, Virginia, United States, 20037

Sponsors and Collaborators

Incyte Corporation

Investigators

Study Director:

Richard Levy, MD

Incyte Corporation

More Information

No publications provided

Responsible Party:	Rich Levy, MD, Incyte Corporation
ClinicalTrials.gov Identifier:	NCT00393120 History of Changes
Other Study ID Numbers:	INCB 9471-201, INCB 9471-201, IND No.69,030
Study First Received:	October 24, 2006
Last Updated:	January 20, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Incyte Corporation:

HIV-infection
viral load
CCR5

viral tropism
HIV-1 infection
Treatment Naive

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases

Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on May 19, 2013