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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PRO 140 | Active Comparator | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PRO 140 | Drug | PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | From baseline visit to week 1 visit |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
This measure includes only the 24 participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Options |
| Measure | Description | Time Frame |
|---|---|---|
| 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# |
Inclusion Criteria:
Males and females, age ≥ 18 years
Exclusive CCR5-tropic virus at Screening Visit
Have a history of at least 3 months on current antiretroviral regimen
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.
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.
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.
Laboratory values at Screening of:
Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator
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.
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:
Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus
Patients with no viable treatment options (≤ 1 fully active drug)
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.
Laboratory test values of ≥ grade 3 DAIDS laboratory abnormality with the exception of the absolute CD4+ count criterion of < 200/mm3
Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study
Unexplained fever or clinically significant illness within 1 week prior to the first study dose
Any vaccination within 2 weeks prior to the first study dose.
Subjects weighing < 35kg
History of anaphylaxis
History of Bleeding Disorder or patients on anti-coagulant therapy
Participation in an experimental drug trial(s) within 30 days of the Screening Visit or during the study
Any known allergy or antibodies to the study drug or excipients
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:
Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy
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| Name | Affiliation | Role |
|---|---|---|
| Edwin DeJesus, MD, FACP, | Orlando Immunology Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CD02 Investigational site | Fountain Valley | California | 92708 | United States | ||
| CD02 Investigational site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39972543 | Derived | Gathe JC, Dejesus E, Ramgopal MN, Rolle CP, Yang OO, Sanchez WE, Lalezari JP, Krishen A, Sacha JB, Hansen SG, Meidling J. Leronlimab Treatment for Multidrug-Resistant HIV-1 (OPTIMIZE): A Randomized, Double-Blind, Placebo-Controlled Trial. J Acquir Immune Defic Syndr. 2025 Jun 1;99(2):185-194. doi: 10.1097/QAI.0000000000003648. |
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365 participants were screened.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part 1 One-week Randomized |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 8, 2018 | Jul 20, 2022 |
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| Placebo | Drug |
|
| Optimized Background Regimen | Drug | Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history. |
|
|
| 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: 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:
This measure includes only the 28 participants with resistance to ART drugs within three drug classes | From baseline visit to week 1 visit |
| 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. | From baseline visit to week 1 visit |
| 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 | 25 weeks |
| 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. | 25 weeks |
| 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. | 25 weeks |
| 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. | From baseline visit to week 1 visit |
| 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. | 25 weeks |
| 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 | From baseline visit to week 1 visit |
| 25 weeks |
| 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. | 25 weeks |
| 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. | 25 weeks |
| 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. | 25 weeks |
| Long Beach |
| California |
| 90813 |
| United States |
| CD02 Investigational site | Los Angeles | California | 90008 | United States |
| CD02 Investigational Site | Los Angeles | California | 90036 | United States |
| CD02 Investigational site | Palm Springs | California | 92262 | United States |
| CD02 Investigational Site | San Francisco | California | 94115 | United States |
| CD02 Investigational site | San Francisco | California | 94118 | United States |
| CD02 Investigational Site | New Haven | Connecticut | 06510 | United States |
| CD02 Investigational site | Norwalk | Connecticut | 06850 | United States |
| CD02 Investigational Site | Washington D.C. | District of Columbia | 20009 | United States |
| CD02 Investigational site | Washington D.C. | District of Columbia | 20017 | United States |
| CD02 Investigational Site | Clearwater | Florida | 33761 | United States |
| CD02 Investigational site | Ft. Pierce | Florida | 34982 | United States |
| CD02 Investigational site | Miami | Florida | 20852 | United States |
| CD02 Investigational site | Miami | Florida | 33136 | United States |
| CD02 Investigational Site | Miami | Florida | 33169 | United States |
| CD02 Investigational site | Miami Beach | Florida | 33139 | United States |
| CD02 Investigational site | Orlando | Florida | 32803 | United States |
| CD02 Investigational site | West Palm Beach | Florida | 33401 | United States |
| CD02 Investigational site | Chicago | Illinois | 60613 | United States |
| CD02 Investigational site | Wichita | Kansas | 67214 | United States |
| E Study Site | Las Vegas | Nevada | 89109 | United States |
| CD02 Investigational site | New York | New York | 10001 | United States |
| CD02 Investigational site | New York | New York | 10011 | United States |
| CD02 Investigational site | Syracuse | New York | 13210 | United States |
| CD02 Investigational site | Charlotte | North Carolina | 28226 | United States |
| CD02 Investigational site | Cincinnati | Ohio | 45267 | United States |
| CD02 Investigational Site | Austin | Texas | 78705 | United States |
| CD02 Investigational Site | Bellaire | Texas | 77301 | United States |
| CD02 Investigational site | Dallas | Texas | 75231 | United States |
| CD02 Investigational Site | Houston | Texas | 77004 | United States |
| CD02 Investigational site | Houston | Texas | 77098 | United States |
| CD02 Investigational Site | Annandale | Virginia | 22003 | United States |
| CD02 Investigational Site | Spokane | Washington | 99202 | United States |
| CD02 Investigational site | Ponce | PR | 00716-2347 | Puerto Rico |
| CD02 Investigational site | San Juan | 00909 | Puerto Rico |
| FG001 | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| Part 2 Open Label Treatment Period |
|
|
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
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Time since HIV Diagnosis | Mean | Standard Deviation | years |
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| Lowest CD4+ Cell Count | Count of Participants | Participants |
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| Number of ART Drug Exposure Prior to Enrollment | Mean | Standard Deviation | Number of ART Drugs prior to enrolment |
| |||||||||||||||
| Number of ART Drug with Documented Resistance | Mean | Standard Deviation | Number of ART drugs with resistance |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | 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 | Posted | Number | Proportion of subjects | From baseline visit to week 1 visit |
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| 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:
This measure includes only the 24 participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Options | The total number of participants in the study ITT population, 52, is further stratified into two subgroups as follows:
This measure includes only the 24 participants with Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option | Posted | Number | Proportion of participants | From baseline visit to week 1 visit |
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| 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:
This measure includes only the 28 participants with resistance to ART drugs within three drug classes | The total number of participants in the study ITT population, 52, is further stratified into two subgroups as follows:
This measure includes only the 28 participants with resistance to ART drugs within three drug classes | Posted | Number | Proportion of participants | From baseline visit to week 1 visit |
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| 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. | 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. | Posted | Mean | Standard Deviation | Log10 Copies/mL | From baseline visit to week 1 visit |
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| 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 | 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 | Posted | Count of Participants | Participants | 25 weeks |
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| 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. | 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 | Posted | Count of Participants | Participants | 25 weeks |
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| 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. | 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 | Posted | Mean | Standard Deviation | Log10 copies/mL | 25 weeks |
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| 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. | 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 | Posted | Mean | Standard Deviation | CD4 Cell Count | From baseline visit to week 1 visit |
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| 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. | 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. | Posted | Mean | Standard Deviation | CD4 Cell Count | 25 weeks |
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| 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 | 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 | Posted | Number | Proportion of participants | From baseline visit to week 1 visit |
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| 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# | 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. | Posted | Mean | Standard Deviation | Units on a scale | 25 weeks |
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| 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. | 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. | Posted | Number | Number of Adverse Events | 25 weeks |
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| 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. | Posted | Number | Number of Serious Adverse Events | 25 weeks |
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| 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. | Posted | Count of Participants | Participants | 25 weeks |
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25 weeks
Adverse events were systematically assessed through documented symptom-directed physical examinations, vital sign evaluation and injection site reaction evaluations performed at treatment and follow-up visits. All information is collected on case report forms.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
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| EG000 | Pro 140 Weekly for 1 Week | 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. | 0 | 25 | 0 | 25 | 2 | 25 |
| EG001 | Placebo Weekly for 1 Week | 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. Placebo Optimized Background Regimen: Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history. | 0 | 27 | 0 | 27 | 2 | 27 |
| EG002 | Part 2 PRO 140 Open Label for 24 Weeks | 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. | 0 | 52 | 8 | 52 | 34 | 52 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
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| Pneumonia | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Mycobacterium avium complex infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Septic shock | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
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| Malnutrition | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
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| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Systematic Assessment |
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| Convulsion | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Grand mal convulsion | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Schizoaffective disorder | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA (17.0) | Non-systematic Assessment |
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| Injection site haemorrhage | General disorders | MedDRA (17.0) | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Injection site bruising | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Acute sinusitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
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| Malnutrition | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (17.0) | Systematic Assessment |
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Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joseph Meidling Senior Director Clinical Operations | CytoDyn | (360) 980-8524 | jmeidling@cytodyn.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 9, 2018 | Jul 20, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| C420063 | leronlimab |
Not provided
Not provided
Not provided
| Subject non compliant |
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| Lost to Follow-up |
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| Adverse Event |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| 200-500 cells/mm^3 |
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| >500 cells/mm^3 |
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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. A) Resistance to ART drugs within two drug class with limited treatment option. |
| OG001 | 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 A) Resistance to ART drugs within two drug class with limited treatment option. |
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| OG001 | 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 A) Resistance to ART drugs within three drug classes |
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| OG001 | 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. |
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