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

Incyte

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: Placebo comparator; Drug: INCB009471

Study type: Interventional

Funder types: Industry

Identifiers

NCT00393120

INCB 9471-201 (Other Identifier)

IND No.69,030

Details and patient eligibility

About

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

Enrollment: 45 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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45 participants in 3 patient groups, including a placebo group

Treatment A - INCB009471 100mg IR

Experimental group

Description:

INCB009471, 100 mg IR orally once daily

Treatment:

Drug: INCB009471

Drug: INCB009471

Treatment B - INCB009471 300mg SR

Experimental group

Description:

INCB009471, 300 mg SR orally once daily

Treatment:

Drug: INCB009471

Drug: INCB009471

Treatment C - Placebo

Placebo Comparator group

Description:

Placebo matching INCB009471

Treatment:

Drug: Placebo comparator