HIV -1 Infection, HIV Infections
Conditions
Keywords
HIV, Treatment Naïve
Brief summary
The purpose of this study is: 1. To assess the antiviral activity of PRO 140 2. To assess the safety and tolerability of PRO 140 3. To generate additional PK, PD and safety data of PRO 140
Interventions
DRUGPRO 140 (humanized monoclonal antibody to CCR5)
DRUGPlacebo Comparator
Sponsors
CytoDyn, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males & females, age ≥ 18 years (or minimum adult age as determined by local regulatory authorities) 2. Screening plasma HIV-1 RNA ≥ 5,000 copies/mL 3. CD4+ lymphocyte cell count ≥ 300 cells/mm3 and no documented count \< or = 250 cells/mm3 4. Has not taken any antiretroviral therapy (ART) w/in 12 wks of Early Screening Visit 5. Exclusive CCR5-tropic virus as determined by Trofile™ Assay at Early Screening Visit 6. Clinically normal or not clinically significant (NCS) resting electrocardiogram 7. Women of reproductive potential must have a negative serum pregnancy test at Late Screening Visit & a negative urine pregnancy test w/in 72 hrs prior to first dose of study medication, & be non-lactating. Male & female subjects must agree not to participate in a conception process from Early Screening Visit through Day 59.
Exclusion criteria
1. CXCR4 tropic virus or dual/mixed tropic (R5X4) virus determined by the Trofile™ Assay. 2. Females who are pregnant, lactating or breastfeeding, or who plan to become pregnant during the study. 3. History of active hepatitis within the previous 24 wks 4. Prior use of any entry, attachment, CCR5 co-receptor or fusion inhibitor, including PRO 140, experimental or approved. 5. Any immunization or vaccination (including influenza vaccine) within 30 days prior to administration of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Change in Viral Load Following Initiation of Treatment (Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL). | 59 days | The primary end point was the maximum change from baseline in viral load following initiation of treatment, defined as HIV-1 copies/mL, measured by the Roche Amplicor HIV-1 Monitor UltraSensitive™ Test (lower limit of detection \[LLD\] = 48 copies/mL). |
Countries
United States
Participant flow
Recruitment details
Recruitment started March 2008 and ended November 2008
Pre-assignment details
There was a screening period of up to 12 weeks. Subjects had to be infected with CCR5-tropic human immunodeficiency virus type 1 (HIV-1)or they were excluded from the study.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 PRO 140 - 162 mg for three single SC doses: Days 1, 8, and 15 | 11 |
| Arm 2 PRO 140 - 324 mg for three single SC doses: Days 1, 8 and 15 | 11 |
| Arm 3 PRO 140 - 324 mg for two single SC doses: Days 1 and 15 plus one SC dose of placebo at Day 8 | 12 |
| Arm 4 Placebo for three single SC doses: Days 1, 8 and 15 | 10 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1 | Arm 2 | Arm 3 | Arm 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 11 Participants | 12 Participants | 10 Participants | 44 Participants |
| Age, Continuous | 38.5 years STANDARD_DEVIATION 5.13 | 41.9 years STANDARD_DEVIATION 5.46 | 46.4 years STANDARD_DEVIATION 8.18 | 42.4 years STANDARD_DEVIATION 7.44 | 42.4 years STANDARD_DEVIATION 7.09 |
| Region of Enrollment United States | 11 participants | 11 participants | 12 participants | 10 participants | 44 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 11 Participants | 9 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 11 | 10 / 11 | 11 / 12 | 10 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 3 / 12 | 0 / 10 |
Outcome results
Primary
Maximum Change in Viral Load Following Initiation of Treatment (Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL).
The primary end point was the maximum change from baseline in viral load following initiation of treatment, defined as HIV-1 copies/mL, measured by the Roche Amplicor HIV-1 Monitor UltraSensitive™ Test (lower limit of detection \[LLD\] = 48 copies/mL).
Time frame: 59 days
Population: All randomized subjects who received one dose of study drug were considered intent-to-treat (ITT) subjects and were analyzed for efficacy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Maximum Change in Viral Load Following Initiation of Treatment (Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL). | -0.99 Log10copies/HIV-1 RNA/mL | Standard Deviation 0.558 |
| Arm 2 | Maximum Change in Viral Load Following Initiation of Treatment (Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL). | -1.65 Log10copies/HIV-1 RNA/mL | Standard Deviation 0.571 |
| Arm 3 | Maximum Change in Viral Load Following Initiation of Treatment (Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL). | -1.37 Log10copies/HIV-1 RNA/mL | Standard Deviation 0.891 |
| Arm 4 | Maximum Change in Viral Load Following Initiation of Treatment (Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL). | -0.23 Log10copies/HIV-1 RNA/mL | Standard Deviation 0.285 |