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

This study has been completed.
Sponsor:
Information provided by:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT00393120
First received: October 24, 2006
Last updated: January 20, 2012
Last verified: January 2012
  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:

  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

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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 20, 2014