PRO 140 for Human Immunodeficiency Virus Infection

Study Overview
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Brief Summary
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PRO 140 2103 is a multicenter, randomized parallel group study, conducted in male and female adult subjects infected with CCR5-tropic HIV-1.

Detailed Description
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Protocol PRO 140 2103 is a multicenter, randomized parallel group study, conducted in approximately 40 male and female adult subjects (n=10/treatment group) infected with CCR5-tropic HIV-1. Subjects will be randomized into one of four treatment groups. Blood samples for drug concentrations, PD variables, and efficacy variables will be obtained over a 59-day period following initiation of dosing. Safety will be monitored throughout the course of the study.

Official Title
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PRO 140 2103: A Phase 2a, Randomized Study of PRO 140 by Subcutaneous Injection in Adult Subjects With Human Immunodeficiency Virus Type 1 Infection

Conditions
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HIV

Intervention / Treatment
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* Biological: PRO 140


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, age ≥18 years Has not taken any antiretroviral therapy (ART) within 12 weeks of the early screening visit Screening plasma HIV-1 RNA ≥ 5,000 copies/mL CD4+ lymphocyte cell count ≥500 cells/mm3 and no documented count less than or equal to 250 cells/mm3 Exclusive CCR5-tropic virus as determined by as determined by the Enhanced Sensitivity Trofile™ HIV Tropism Assay Clinically normal resting 12-lead ECG at screening visit Women of reproductive potential must have a negative serum pregnancy test at Late Screening Visit. Within hours prior to receiving the first dose of study drug, women of reproductive potential must have a negative urine pregnancy test. Male and female subjects must agree not to participate in a conception process and agree to use one barrier method of contraception plus one other highly reliable contraceptive method from the early screening visit through three weeks after the last administered subcutaneous dose of PRO 140. Exclusion Criteria: CXCR4-tropic virus, dual/mixed tropic (R5X4) virus as determined by the Enhanced Sensitivity Trofile™ HIV Tropism Assay Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study Diagnosis of acute viral hepatitis (defined as any active infection with hepatitis A or a new diagnosis of hepatitis B or C within 24 weeks of dosing) Chronic hepatitis Prior use of any entry, attachment, CCR5 coreceptor, or fusion inhibitor, including PRO 140, experimental or approved Any immunization or vaccination (including influenza vaccine) within 30 days prior to administration of study drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Arm 1<br>PRO 140: one SC dose, 350 mg (day 1), followed by two single SC doses, 350 mg each (days 8 and 15) Intervention: Drug: PRO 140 (humanized monoclonal antibody to CCR5) | Biological: PRO 140<br>* Humanized monoclonal antibody to CCR5<br>|
| Active Comparator: Treatment Arm 2<br>PRO 140: one SC loading dose, 700 mg (day 1), followed by two single SC doses, 350 mg each (days 8 and 15) Intervention: Drug: PRO 140 (humanized monoclonal antibody to CCR5) | Biological: PRO 140<br>* Humanized monoclonal antibody to CCR5<br>|
| Active Comparator: Treatment Arm 3<br>PRO 140: one SC loading dose, 700 mg (day 1), followed by one single SC dose 350 mg (day 15) Intervention: Drug: PRO 140 (humanized monoclonal antibody to CCR5) | Biological: PRO 140<br>* Humanized monoclonal antibody to CCR5<br>|
| Active Comparator: Treatment Arm 4<br>PRO 140: one SC dose, 700 mg (day 1) Intervention: Drug: PRO 140 (humanized monoclonal antibody to CCR5) | Biological: PRO 140<br>* Humanized monoclonal antibody to CCR5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum change in viral load following initiation of different dosing regimens of PRO140 | Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL | 59 days |