HIV
Conditions
Brief summary
This is a Phase 2b/3, multi-center, two part study, designed to evaluate the efficacy, safety, and tolerability of PRO 140 in conjunction with existing ART (failing regimen) for one week and Optimized Background Therapy (OBT) for 24 weeks respectively. Study population includes treatment-experienced HIV-infected patients with CCR5-tropic virus who demonstrates evidence of HIV-1 replication despite ongoing antiretroviral therapy with documented genotypic or phenotypic resistance to ART drugs within three drug classes (or within two or more drug classes with limited treatment options).The options may be limited as a result of drug antiviral class cross-resistance or documented treatment intolerance.
Detailed description
PRO 140, in combination with other antiretroviral agents, is indicated for treatment experienced adult HIV-1 patients infected with CCR5-tropic virus. These patients must demonstrate evidence of HIV-1 replication despite ongoing antiretroviral therapy and have documented genotypic or phenotypic resistance to at least one ART drug within three drug classes (or within two or more drug classes with limited treatment option). The options may be limited as a result of drug antiviral class cross-resistance, documented treatment intolerance, documented objective assessments such as renal or hepatic insufficiency (e.g. high creatinine at baseline, limiting treatment options due to potential for toxicity), past adverse reactions such as hypersensitivity reactions or neuropsychiatric issues that could limit use of currently approved drugs. Study population includes treatment-experienced HIV-infected patients with CCR5-tropic virus who demonstrates evidence of HIV-1 replication despite ongoing antiretroviral therapy with documented genotypic or phenotypic resistance to ART drugs within three drug classes (or within two drug classes with limited treatment option). Enrollment will be stratified to have HIV-1 virus resistant to ART drugs within three drug classes or within two drug classes with limited treatment option. The primary objective is to assess the efficacy, clinical safety and tolerability parameters of PRO 140 compared to placebo in reducing HIV-1 viral load during the 1-week double-blind treatment period. The secondary objectives of the trial are to assess the efficacy, clinical safety and tolerability parameters of PRO 140 in combination with Optimized Background Therapy during the 24-week single-arm, open-label treatment period.
Interventions
DRUGPRO 140
PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.
DRUGPlacebo
Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history.
Sponsors
CytoDyn, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females, age ≥ 18 years 2. Exclusive CCR5-tropic virus at Screening Visit 3. Have a history of at least 3 months on current antiretroviral regimen 4. Treatment-experienced HIV-infected patients with documented genotypic or phenotypic resistance to at least one ART drug within three drug classes OR Treatment-experienced HIV-infected patients with documented genotypic or phenotypic resistance to at least one ART drug within two drug classes and have limited treatment options. The options may be limited as a result of drug antiretroviral class cross-resistance or documented treatment intolerance. 5. Be willing to remain on treatment without any changes or additions to the OBT regimen, except for toxicity management or upon meeting criteria for treatment failure. 6. Plasma HIV-1 RNA ≥ 400 copies/mL at Screening Visit and documented detectable viral load (HIV-1 RNA \>50 copies/ml) within the last 3 months prior to Screening Visit. 7. Laboratory values at Screening of: * Absolute neutrophil count (ANC) ≥ 750/mm3 * Hemoglobin (Hb) ≥ 10.5 gm/dL (male) or ≥ 9.5 gm/dL (female) * Platelets ≥ 75,000 /mm3 * Serum alanine transaminase (SGPT/ALT) \< 5 x upper limit of normal (ULN) * Serum aspartate transaminase (SGOT/AST) \< 5 x ULN * Bilirubin (total) \< 2.5 x ULN unless Gilbert's disease is present or subject is receiving atazanavir in the absence of other evidence of significant liver disease * Creatinine ≤ 1.5 x ULN 8. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator 9. Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives \[male condom, female condom, or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings\], and intrauterine devices) during the course of the study (excluding women who are not of childbearing potential and men who have been sterilized). Females of childbearing potential must have a negative serum pregnancy test at Screening visit and negative urine pregnancy test prior to receiving the first dose of study drug. 10. Willing and able to participate in all aspects of the study, including use of SC medication, completion of subjective evaluations, attendance at scheduled clinic visits, and compliance with all protocol requirements as evidenced by providing written informed consent. Note: Subjects diagnosed with either substance dependence or substance abuse or any history of a concomitant condition (e.g., medical, psychologic, or psychiatric) may be enrolled if in the opinion of site investigator these circumstances would not interfere with the subject's successful completion of the study requirements.
Exclusion criteria
1. Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus 2. Patients with no viable treatment options (≤ 1 fully active drug) 3. Any active infection or malignancy requiring acute therapy (with the exception of local cutaneous Kaposi's sarcoma) Note: Subjects infected by the hepatitis B virus or early stage hepatitis C virus will be eligible for the study. 4. Laboratory test values of ≥ grade 3 DAIDS laboratory abnormality with the exception of the absolute CD4+ count criterion of \< 200/mm3 5. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study 6. Unexplained fever or clinically significant illness within 1 week prior to the first study dose 7. Any vaccination within 2 weeks prior to the first study dose. 8. Subjects weighing \< 35kg 9. History of anaphylaxis 10. History of Bleeding Disorder or patients on anti-coagulant therapy 11. Participation in an experimental drug trial(s) within 30 days of the Screening Visit or during the study 12. Any known allergy or antibodies to the study drug or excipients 13. Treatment with any of the following: * Radiation or cytotoxic chemotherapy with 30 days prior to the Screening Visit or during the study * Immunosuppressants within 60 days prior to the Screening Visit or during the study * Immunomodulating agents (e.g., interleukins, interferons), hydroxyurea, or foscarnet within 60 days prior to the Screening Visit or during the study * Oral or parenteral corticosteroids within 30 days prior to the Screening Visit or during the study. Subjects on chronic steroid therapy \> 5 mg/day will be excluded with the following exception: * Subjects on inhaled, nasal, or topical steroids will not be excluded. 14. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period | From baseline visit to week 1 visit | The primary efficacy endpoint will be proportion of participants with a 0.5 log10 or greater reduction in HIV-1 RNA viral load from baseline at the end of the one week double-blind treatment period (Part 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving HIV-1 RNA < 400 Copies/mL at Week 25 for All Patients and Within Each Stratum | 25 weeks | The number and percentages of subjects achieving HIV-1 RNA \< 400 copies/mL at Week 25, from the open label portion of the study, are presented |
| Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at Week 25 for All Patients and Within Each Stratum | 25 weeks | The raw and change from baseline in HIV-1 RNA levels (log10 copies/mL) at Week 25 was to be summarized for each week during the treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded. |
| Mean Change From Baseline in CD4 Cell Count at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | From baseline visit to week 1 visit | The raw and change from baseline in CD4 cell count at the end of the 1-week double blind treatment period was to be summarized by treatment group for the first week during the double-blind treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded. |
| Mean Change From Baseline in CD4 Cell Count at Week 25 for All Patients and Within Each Stratum | 25 weeks | The raw and change from baseline in CD4 cell count at Week 25 was to be summarized for each week during the treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded. |
| Proportion of Participants With ≥ 1 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | From baseline visit to week 1 visit | The number and percentage of subjects with a ≥ 1log10 or greater reduction in HIV-1 RNA viral load from baseline was to be presented for the two (2) treatment groups. The analysis of change in viral load was done for subjects with ≥ 1.0 log10 reduction in HIV-1 RNA after the first week of treatment. The analysis is presented for the ITT population |
| Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option. | From baseline visit to week 1 visit | Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period, stratified to each group: a. resistance to ART drugs within two drug class with limited treatment option (N = 24). This outcome measures the proportion of participants that are classified as having a resistance to ART drugs within two drug classes and with limited treatment options with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period . The total number of participants in the study ITT population, 52, is further stratified into two subgroups: 1. Participants with resistance to ART Drugs Within Two Drug Class With Limited Treatment Option (N = 24) 2. Participants with resistance to ART Drugs Within Three Drug Classes (N = 28) This measure includes only the 24 participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Options |
| Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Three Drug Classes | From baseline visit to week 1 visit | Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period, stratified to each group: a. Resistance to ART drugs within three drug classes (N = 28) This outcome measures the proportion of participants that are classified as having a resistance to ART drugs within two drug classes and with limited treatment options with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period . The total number of participants in the study ITT population, 52, is further stratified into two subgroups as follows: 1. Participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option (N = 24) 2. Participants with resistance to ART Drugs Within Three Drug Classes (N = 28) This measure includes only the 28 participants with resistance to ART drugs within three drug classes |
| Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | From baseline visit to week 1 visit | The raw and change from baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the 1-week double-blind treatment period was to be summarized by treatment group for the first week during the double-blind treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded. The change from baseline in HIV-1 RNA levels was to be compared between the two (2) groups using Analysis of covariance (ANCOVA) with the stratification factor (i.e., Resistance to ART drugs at the time of randomization) included in the model. |
| Percentage and Number of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 25 for All Patients and Within Each Stratum | 25 weeks | The number and percentages of subjects achieving HIV-1 RNA \< 50 copies/mL at Week 25 are presented. This is from the 24 week open label portion of the of the trial. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Treatment-Emergent Serious Adverse Events | 25 weeks | The incidence of serious adverse events (SAEs) by relationship to the study treatment. In total, there were 16 SAEs reported for eight (8) subjects (15.4%, 8/52). Thirteen of the SAEs were determined to be Unrelated, three were determined to be Unlikely Related to study treatment. |
| Emergence of Dual/Mixed (D/M)- and CXCR4-tropic Virus in Patients Who Had Exclusive CCR5-tropic Virus at Study Entry. | 25 weeks | The number of study participants who had exclusive CCR5-tropic virus at study entry and subsequently developed Dual/Mixed (D/M)- and CXCR4-tropic virus at any time during study treatment while receiving PRO 140. |
| Frequency of Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale | 25 weeks | The investigator was to carefully evaluate the comments of each subject and the response to treatment in order to judge the true nature and severity of the AE. The question of the relationship of AEs to study drug should have been determined by the investigator after thorough consideration of all available facts. To assess severity, the investigator was to use the DAIDS AE grading table for adverse events as well as any injection site reactions. |
| Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | 25 weeks | Assessments of subject-perceived injection site pain using the Pain Visual Analog Scale (VAS) were performed during each visit to the clinic for a study visit. Beginning at Treatment Visit 2 (T2), subjects were asked to mark the point that best represents the average pain intensity over the past week at the injection site on a horizontal line (100 mm in length) anchored by the following word descriptors at each end, no pain on the left side and pain as bad as it could possibly be on the right side of the line. The subject marks on the line or by pointing to a position on the line the point that they feel represents their perception of their pain state. The VAS score is determined by measuring in millimeters from the left-hand end of the line to the point that the patient marks The scale range is 0mm to 100 mm, with 0 mm = No Pain and 100 mm = Pain as bad as it could possibly be. In this measurement, a lower number corresponds to less perceived pain. T# = Visit Week# |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled from U.S. sites only. The first participant was enrolled on 21 October 2015 and the last subject completed the study on 25 July 2018.
Pre-assignment details
365 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| PRO 140 PRO140 350mg weekly SC Inj. + existing ART for one week. After one week, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy.
PRO 140: PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.
Optimized Background Regimen: Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history. | 25 |
| Placebo Placebo weekly SC Inj. + existing ART for one week. After one week, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy.
Placebo
Optimized Background Regimen: Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history. | 27 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part 1 One-week Randomized | Lost to Follow-up | 0 | 1 |
| Part 2 Open Label Treatment Period | Adverse Event | 0 | 1 |
| Part 2 Open Label Treatment Period | Lost to Follow-up | 0 | 1 |
| Part 2 Open Label Treatment Period | Non-medical | 0 | 1 |
| Part 2 Open Label Treatment Period | Subject non compliant | 0 | 1 |
| Part 2 Open Label Treatment Period | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | PRO 140 |
|---|---|---|---|
| Age, Continuous | 52.4 years STANDARD_DEVIATION 7.6 | 52.4 years STANDARD_DEVIATION 6.7 | 52.4 years STANDARD_DEVIATION 8.6 |
| Lowest CD4+ Cell Count 200-500 cells/mm^3 | 27 Participants | 14 Participants | 13 Participants |
| Lowest CD4+ Cell Count <200 cells/mm^3 | 22 Participants | 12 Participants | 10 Participants |
| Lowest CD4+ Cell Count >500 cells/mm^3 | 3 Participants | 1 Participants | 2 Participants |
| Number of ART Drug Exposure Prior to Enrollment | 10.7 Number of ART Drugs prior to enrolment STANDARD_DEVIATION 4.6 | 9.6 Number of ART Drugs prior to enrolment STANDARD_DEVIATION 4.2 | 11.8 Number of ART Drugs prior to enrolment STANDARD_DEVIATION 4.8 |
| Number of ART Drug with Documented Resistance | 9.1 Number of ART drugs with resistance STANDARD_DEVIATION 4.6 | 8.8 Number of ART drugs with resistance STANDARD_DEVIATION 3.3 | 9.4 Number of ART drugs with resistance STANDARD_DEVIATION 5.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 13 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 13 Participants | 14 Participants |
| Region of Enrollment United States | 52 participants | 27 participants | 25 participants |
| Sex: Female, Male Female | 14 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 38 Participants | 21 Participants | 17 Participants |
| Time since HIV Diagnosis | 20.4 years STANDARD_DEVIATION 9.4 | 20.8 years STANDARD_DEVIATION 9.4 | 20.0 years STANDARD_DEVIATION 9.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 27 | 0 / 52 |
| other Total, other adverse events | 2 / 25 | 2 / 27 | 34 / 52 |
| serious Total, serious adverse events | 0 / 25 | 0 / 27 | 8 / 52 |
Outcome results
Primary
Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period
The primary efficacy endpoint will be proportion of participants with a 0.5 log10 or greater reduction in HIV-1 RNA viral load from baseline at the end of the one week double-blind treatment period (Part 1).
Time frame: From baseline visit to week 1 visit
Population: The primary population used for this analysis was the ITT population, defined as subjects who were randomized and had received at least one (1) dose of leronlimab (PRO 140) or placebo
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO 140 | Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period | With >= 0.5 LOG10 IN HIV-1 RNA VIRAL Load Change from Baseline | .64 Proportion of subjects |
| PRO 140 | Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period | Without >= 0.5 LOG10 IN HIV-1 RNA VIRAL Load Change from Baseline | .36 Proportion of subjects |
| Placebo | Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period | With >= 0.5 LOG10 IN HIV-1 RNA VIRAL Load Change from Baseline | .23 Proportion of subjects |
| Placebo | Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period | Without >= 0.5 LOG10 IN HIV-1 RNA VIRAL Load Change from Baseline | .77 Proportion of subjects |
p-value: 0.0032Fisher Exact
Secondary
Mean Change From Baseline in CD4 Cell Count at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum
The raw and change from baseline in CD4 cell count at the end of the 1-week double blind treatment period was to be summarized by treatment group for the first week during the double-blind treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded.
Time frame: From baseline visit to week 1 visit
Population: The Intent-to-Treat (ITT) population was defined as the set of subjects who were randomized and received at least one (1) dose of leronlimab (PRO 140) or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Mean Change From Baseline in CD4 Cell Count at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | 41.1 CD4 Cell Count | Standard Deviation 154 |
| Placebo | Mean Change From Baseline in CD4 Cell Count at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | 25 CD4 Cell Count | Standard Deviation 131 |
Comparison: The raw and change from baseline in CD4 cell count at the end of the 1-week double blind treatment period was to be summarized by treatment group for the first week during the double-blind treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded.p-value: 0.7123ANCOVA
Secondary
Mean Change From Baseline in CD4 Cell Count at Week 25 for All Patients and Within Each Stratum
The raw and change from baseline in CD4 cell count at Week 25 was to be summarized for each week during the treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded.
Time frame: 25 weeks
Population: The Intent-to-Treat (ITT) population was defined as the set of subjects who were randomized and received at least one (1) dose of leronlimab (PRO 140) or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Mean Change From Baseline in CD4 Cell Count at Week 25 for All Patients and Within Each Stratum | 85.9 CD4 Cell Count | Standard Deviation 175.2 |
Secondary
Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum
The raw and change from baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the 1-week double-blind treatment period was to be summarized by treatment group for the first week during the double-blind treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded. The change from baseline in HIV-1 RNA levels was to be compared between the two (2) groups using Analysis of covariance (ANCOVA) with the stratification factor (i.e., Resistance to ART drugs at the time of randomization) included in the model.
Time frame: From baseline visit to week 1 visit
Population: Intent-to-Treat: The Intent-to-Treat (ITT) population was defined as the set of subjects who were randomized and had received at least one (1) dose of leronlimab (PRO 140) or placebo. This population was to be used as the primary analysis population for the primary and secondary endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | 0.6 Log10 Copies/mL | Standard Deviation 0.45 |
| Placebo | Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | 0.1 Log10 Copies/mL | Standard Deviation 0.51 |
p-value: 0.0013ANCOVA
Secondary
Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at Week 25 for All Patients and Within Each Stratum
The raw and change from baseline in HIV-1 RNA levels (log10 copies/mL) at Week 25 was to be summarized for each week during the treatment phase. For change from baseline summaries, subjects with an undefined change from baseline, because of missing data, were to be excluded.
Time frame: 25 weeks
Population: The Intent-to-Treat (ITT) population was defined as the set of subjects who were randomized and received at least one (1) dose of leronlimab (PRO 140) or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at Week 25 for All Patients and Within Each Stratum | 2.4 Log10 copies/mL | Standard Deviation 1.42 |
Secondary
Percentage and Number of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 25 for All Patients and Within Each Stratum
The number and percentages of subjects achieving HIV-1 RNA \< 50 copies/mL at Week 25 are presented. This is from the 24 week open label portion of the of the trial.
Time frame: 25 weeks
Population: The Intent-to-Treat (ITT) population was defined as the set of subjects who were randomized and received at least one (1) dose of leronlimab (PRO 140) or placebo
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRO 140 | Percentage and Number of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 25 for All Patients and Within Each Stratum | With HIV-1 RNA < 50 Copies/mL at Week 25 | 32 Participants |
| PRO 140 | Percentage and Number of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 25 for All Patients and Within Each Stratum | Without HIV-1 RNA < 50 Copies/mL at Week 25 | 8 Participants |
| PRO 140 | Percentage and Number of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 25 for All Patients and Within Each Stratum | Missing | 12 Participants |
Secondary
Percentage of Participants Achieving HIV-1 RNA < 400 Copies/mL at Week 25 for All Patients and Within Each Stratum
The number and percentages of subjects achieving HIV-1 RNA \< 400 copies/mL at Week 25, from the open label portion of the study, are presented
Time frame: 25 weeks
Population: The Intent-to-Treat (ITT) population was defined as the set of subjects who were randomized and received at least one (1) dose of leronlimab (PRO 140) or placebo
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRO 140 | Percentage of Participants Achieving HIV-1 RNA < 400 Copies/mL at Week 25 for All Patients and Within Each Stratum | With HIV-1 RNA < 400 Copies/mL at Week 25 | 37 Participants |
| PRO 140 | Percentage of Participants Achieving HIV-1 RNA < 400 Copies/mL at Week 25 for All Patients and Within Each Stratum | Without HIV-1 RNA < 400 Copies/mL at Week 25 | 3 Participants |
| PRO 140 | Percentage of Participants Achieving HIV-1 RNA < 400 Copies/mL at Week 25 for All Patients and Within Each Stratum | Missing | 12 Participants |
Secondary
Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Three Drug Classes
Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period, stratified to each group: a. Resistance to ART drugs within three drug classes (N = 28) This outcome measures the proportion of participants that are classified as having a resistance to ART drugs within two drug classes and with limited treatment options with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period . The total number of participants in the study ITT population, 52, is further stratified into two subgroups as follows: 1. Participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option (N = 24) 2. Participants with resistance to ART Drugs Within Three Drug Classes (N = 28) This measure includes only the 28 participants with resistance to ART drugs within three drug classes
Time frame: From baseline visit to week 1 visit
Population: The total number of participants in the study ITT population, 52, is further stratified into two subgroups as follows:~1. Participants with resistance to ART Drugs Within Two Drug Class With Limited Treatment Options (N = 24)~2. Participants with resistance to ART Drugs Within Three Drug Classes (N = 28)~This measure includes only the 28 participants with resistance to ART drugs within three drug classes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO 140 | Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Three Drug Classes | .5714 Proportion of participants |
| Placebo | Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Three Drug Classes | .2308 Proportion of participants |
p-value: 0.1201Fisher Exact
Secondary
Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option.
Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period, stratified to each group: a. resistance to ART drugs within two drug class with limited treatment option (N = 24). This outcome measures the proportion of participants that are classified as having a resistance to ART drugs within two drug classes and with limited treatment options with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period . The total number of participants in the study ITT population, 52, is further stratified into two subgroups: 1. Participants with resistance to ART Drugs Within Two Drug Class With Limited Treatment Option (N = 24) 2. Participants with resistance to ART Drugs Within Three Drug Classes (N = 28) This measure includes only the 24 participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Options
Time frame: From baseline visit to week 1 visit
Population: The total number of participants in the study ITT population, 52, is further stratified into two subgroups as follows:~1. Participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option (N = 24)~2. Participants with resistance to ART Drugs Within Three Drug Classes (N = 28)~This measure includes only the 24 participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO 140 | Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option. | .7273 Proportion of participants |
| Placebo | Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option. | .2308 Proportion of participants |
p-value: 0.0377Fisher Exact
Secondary
Proportion of Participants With ≥ 1 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum
The number and percentage of subjects with a ≥ 1log10 or greater reduction in HIV-1 RNA viral load from baseline was to be presented for the two (2) treatment groups. The analysis of change in viral load was done for subjects with ≥ 1.0 log10 reduction in HIV-1 RNA after the first week of treatment. The analysis is presented for the ITT population
Time frame: From baseline visit to week 1 visit
Population: The Intent-to-Treat (ITT) population was defined as the set of subjects who were randomized and received at least one (1) dose of leronlimab (PRO 140) or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO 140 | Proportion of Participants With ≥ 1 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | .2 Proportion of participants |
| Placebo | Proportion of Participants With ≥ 1 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum | .0385 Proportion of participants |
p-value: 0.0993Fisher Exact
Other Pre-specified
Emergence of Dual/Mixed (D/M)- and CXCR4-tropic Virus in Patients Who Had Exclusive CCR5-tropic Virus at Study Entry.
The number of study participants who had exclusive CCR5-tropic virus at study entry and subsequently developed Dual/Mixed (D/M)- and CXCR4-tropic virus at any time during study treatment while receiving PRO 140.
Time frame: 25 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRO 140 | Emergence of Dual/Mixed (D/M)- and CXCR4-tropic Virus in Patients Who Had Exclusive CCR5-tropic Virus at Study Entry. | 2 Participants |
Other Pre-specified
Frequency of Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale
The investigator was to carefully evaluate the comments of each subject and the response to treatment in order to judge the true nature and severity of the AE. The question of the relationship of AEs to study drug should have been determined by the investigator after thorough consideration of all available facts. To assess severity, the investigator was to use the DAIDS AE grading table for adverse events as well as any injection site reactions.
Time frame: 25 weeks
Population: The Safety population was defined as all subjects who received at least one (1) dose of leronlimab (PRO 140) or placebo after randomization. This population was used for the analysis of safety parameters.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO 140 | Frequency of Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale | Moderate AEs | 40 Number of Adverse Events |
| PRO 140 | Frequency of Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale | Severe AEs | 15 Number of Adverse Events |
Other Pre-specified
Frequency of Treatment-Emergent Serious Adverse Events
The incidence of serious adverse events (SAEs) by relationship to the study treatment. In total, there were 16 SAEs reported for eight (8) subjects (15.4%, 8/52). Thirteen of the SAEs were determined to be Unrelated, three were determined to be Unlikely Related to study treatment.
Time frame: 25 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO 140 | Frequency of Treatment-Emergent Serious Adverse Events | Unrelated | 13 Number of Serious Adverse Events |
| PRO 140 | Frequency of Treatment-Emergent Serious Adverse Events | Unlikely Related | 3 Number of Serious Adverse Events |
Other Pre-specified
Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions
Assessments of subject-perceived injection site pain using the Pain Visual Analog Scale (VAS) were performed during each visit to the clinic for a study visit. Beginning at Treatment Visit 2 (T2), subjects were asked to mark the point that best represents the average pain intensity over the past week at the injection site on a horizontal line (100 mm in length) anchored by the following word descriptors at each end, no pain on the left side and pain as bad as it could possibly be on the right side of the line. The subject marks on the line or by pointing to a position on the line the point that they feel represents their perception of their pain state. The VAS score is determined by measuring in millimeters from the left-hand end of the line to the point that the patient marks The scale range is 0mm to 100 mm, with 0 mm = No Pain and 100 mm = Pain as bad as it could possibly be. In this measurement, a lower number corresponds to less perceived pain. T# = Visit Week#
Time frame: 25 weeks
Population: Assessments of subject-perceived injection site pain using the Pain Visual Analog Scale (VAS) was performed during each visit to the clinic for a study visit. The number of study participant visits varied each week and N = the number that visited the clinic and were assessed each week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T2 (Week 2) Left Side Injection Site | 1.3 Units on a scale | Standard Deviation 8.5 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T3 (Week 3) Left Side Injection Site | 0.3 Units on a scale | Standard Deviation 1.5 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T3 (Week 3) Right Side Injection Site | 0.2 Units on a scale | Standard Deviation 0.7 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T5 (Week 5) Left Side Injection Site | .7 Units on a scale | Standard Deviation 4 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T11 (Week 11) Left Side Injection Site | .3 Units on a scale | Standard Deviation 1.1 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T11 (Week 11) Right Side Injection Site | .2 Units on a scale | Standard Deviation 1 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T14 (Week 14) Left Side Injection Site | .4 Units on a scale | Standard Deviation 1.7 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T19 (Week 19) Left Side Injection Site | .3 Units on a scale | Standard Deviation 1.3 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T19 (Week 19) Right Side Injection Site | .2 Units on a scale | Standard Deviation 1.3 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T20 (Week 20) Right Side Injection Site | 1.1 Units on a scale | Standard Deviation 6 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T2 (Week 2) Right Side Injection Site | 1.0 Units on a scale | Standard Deviation 7.1 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T4 (Week 4) Left Side Injection Site | 0.4 Units on a scale | Standard Deviation 1.7 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T4 (Week 4) Right Side Injection Site | 0.3 Units on a scale | Standard Deviation 1.1 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T5 (Week 5) Right Side Injection Site | .1 Units on a scale | Standard Deviation 0.6 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T6 (Week 6) Left Side Injection Site | .8 Units on a scale | Standard Deviation 4.8 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T6 (Week 6) Right Side Injection Site | .3 Units on a scale | Standard Deviation 1.7 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T7 (Week 7) Left Side Injection Site | .2 Units on a scale | Standard Deviation 0.9 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T7 (Week 7) Right Side Injection Site | .3 Units on a scale | Standard Deviation 1.7 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T8 (Week 8) Left Side Injection Site | .3 Units on a scale | Standard Deviation 1.3 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T8 (Week 8) Right Side Injection Site | .4 Units on a scale | Standard Deviation 1.5 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T9 (Week 9) Left Side Injection Site | .2 Units on a scale | Standard Deviation 0.8 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T9 (Week 9) Right Side Injection Site | .2 Units on a scale | Standard Deviation 0.9 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T10 (Week 10) Left Side Injection Site | .3 Units on a scale | Standard Deviation 1.1 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T10 (Week 10) Right Side Injection Site | .3 Units on a scale | Standard Deviation 1.1 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T12 (Week 12) Left Side Injection Site | .9 Units on a scale | Standard Deviation 3 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T12 (Week 12) Right Side Injection Site | .8 Units on a scale | Standard Deviation 2.7 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T13 (Week 13) Left Side Injection Site | .1 Units on a scale | Standard Deviation 0.9 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T13 (Week 13) Right Side Injection Site | .1 Units on a scale | Standard Deviation 0.9 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T14 (Week 14) Right Side Injection Site | .4 Units on a scale | Standard Deviation 1.8 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T15 (Week 15) Left Side Injection Site | .1 Units on a scale | Standard Deviation 0.6 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T15 (Week 15) Right Side Injection Site | .2 Units on a scale | Standard Deviation 0.9 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T16 (Week 16) Left Side Injection Site | .4 Units on a scale | Standard Deviation 1.6 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T16 (Week 16) Right Side Injection Site | .2 Units on a scale | Standard Deviation 0.8 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T17 (Week 17) Left Side Injection Site | .1 Units on a scale | Standard Deviation 0.4 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T17 (Week 17) Right Side Injection Site | .1 Units on a scale | Standard Deviation 0.4 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T18 (Week 18) Left Side Injection Site | .2 Units on a scale | Standard Deviation 1.2 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T18 (Week 18) Right Side Injection Site | .3 Units on a scale | Standard Deviation 1.5 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T20 (Week 20) Left Side Injection Site | 1.5 Units on a scale | Standard Deviation 8.9 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T21 (Week 21) Left Side Injection Site | .8 Units on a scale | Standard Deviation 4.5 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T21 (Week 21) Right Side Injection Site | .4 Units on a scale | Standard Deviation 1.8 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T22 (Week 22) Left Side Injection Site | .2 Units on a scale | Standard Deviation 0.9 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T22 (Week 22) Right Side Injection Site | .2 Units on a scale | Standard Deviation 0.8 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T23 (Week 23) Left Side Injection Site | .3 Units on a scale | Standard Deviation 1.7 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T23 (Week 23) Right Side Injection Site | .2 Units on a scale | Standard Deviation 0.9 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T24 (Week 24) Left Side Injection Site | .2 Units on a scale | Standard Deviation 1.4 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T24 (Week 24) Right Side Injection Site | 0 Units on a scale | Standard Deviation 0.2 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T25 (Week 25) Left Side Injection Site | .1 Units on a scale | Standard Deviation 0.6 |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions | T25 (Week 25) Right Side Injection Site | 0 Units on a scale | Standard Deviation 0.3 |