Safety and Efficacy of an Antibody to CCR5 in Individuals With HIV Who Are Not Currently on Antiretroviral Therapy

HIV Infections Clinical Trial

Official title:

A Phase 1, Randomized, Placebo-Controlled, Single-Injection, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ccr5mab004 (Human Monoclonal Igg4 Antibody To Ccr5) in Hiv-1 Seropositive Individuals Who Are Not Receiving Concurrent Antiretroviral Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114699
• Other study ID #: CCR5-HV01
• Status: Completed
• Phase: Phase 1
• First received: June 16, 2005
• Last updated: August 1, 2013
• Start date: April 2005
• Est. completion date: April 2006

Study information

• Verified date: August 2013
• Source: Human Genome Sciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a phase 1, randomized, placebo-controlled, dose-escalation study of CCR5mAb004 in HIV-1 seropositive individuals who are not receiving concurrent antiretroviral therapy. Subjects will be randomly assigned to receive a single intravenous (IV) infusion of one of four dose levels of CCR5mAb004 or matching placebo. A minimum of 10 subjects will be randomized to each cohort at a ratio of 4:1 (active:placebo). A minimum of 40 and maximum of 60 subjects will be enrolled. This study will be conducted at up to 10 sites in the United States.

Subjects in each cohort will be followed for 56 days after study agent administration. The safety, tolerability, and immunogenicity of CCR5mAb004 will be evaluated based on physical examination, adverse event (AE) reporting, and clinical laboratory tests. Blood will be collected at specified times for the determination of CCR5mAb004 serum concentrations, HIV-1 RNA levels, and CD4+ and CD8+ cell counts. If CD4+ cell counts are less than 200 during the study period, the subject should be offered standard-of-care per HIV treatment guidelines that may include the initiation of appropriate anti-retroviral therapy (AVR). CCR5mAb004 pharmacokinetic (PK) and pharmacodynamics (PD) will be measured over the 56-day study period. Anti-CCR5mAb004 antibody titers will be assessed prior to dosing on Day 0 and on Day 28 and Day 56.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• HIV-1 infection confirmed by enzyme immunoassay (EIA) and Western blot.

• Age 18 to 64 years.

• HIV-1 RNA > 5000 copies/mL.

• CD4+ T cell count > 250 cells/uL.

• Treatment naïve, or off antiretroviral treatment for at least 30 days prior to screening and 60 days prior to Day 0

• CCR5 tropism confirmed by R5 PhenoSense assays.

Exclusion Criteria:

• CXCR4 tropic or dual tropic virus at screening.

• Laboratory values of Grade 3 or greater according to the Modified Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Tables.

• History of Category C AIDS-defining illness according to the 1993 Centers for Disease Control and Prevention (CDC) AIDS surveillance definition.

• History of any medical disease or condition that makes the subject (in the opinion of the investigator) unsuitable for the study.

• Malignancy within the past 5 years (except for basal carcinomas of the skin and in situ cancers of the cervix).

• Females who are pregnant or breastfeeding, or who plan to become pregnant during the study.

• Subjects whose dosage or number of prescription medications has changed within 30 days prior to screening

• Positive for hepatitis B surface antigen (HBsAg) or antibody to hepatitis C virus (HCV).

• Positive alcohol or drug screen

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• CCR5mAb004

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	OSU Medical Center	Columbus	Ohio
United States	AIDS Research Alliance	Los Angeles	California
United States	The Orlando Immunology Center	Orlando	Florida
United States	Quest Clinical Research	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Human Genome Sciences Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The major safety endpoints are AE rates and laboratory abnormalities through Day 56.
Secondary	The efficacy endpoints include change from baseline HIV-1 RNA levels (including viral kinetics) through Day 56, and change from baseline CD4+ and CD8+ cell counts through Day 56.