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| Name | Class |
|---|---|
| AbbVie | INDUSTRY |
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The study was conducted to determine if cenicriviroc mesylate (CVC) would decrease vascular inflammation as measured by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging of the aorta and carotid arteries.
This was a double-blind, placebo-controlled phase II clinical trial comparing the intervention of CVC versus placebo for a duration of 24 weeks on arterial inflammation evaluated by FDG-PET/CT imaging.
A total of 110 participants were randomized 2:1 to the CVC arm (Arm A) or placebo for CVC arm (Arm B). Stratification by statin use at randomization ensured even distribution of statin use between the treatment groups.
Analyses were based on the efficacy population: all enrolled participants who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
Analysis of the primary outcome utilized multiple imputation by regression to impute missing data.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CVC arm (Arm A) | Experimental | Participants with pre-existing ART regimen of efavirenz (EFV) took CVC 300 mg. Participants with all other pre-existing ART regimens took CVC 150 mg. |
|
| Placebo for CVC arm (Arm B) | Placebo Comparator | Participants with pre-existing ART regimen of efavirenz (EFV) took placebo for CVC 300 mg. Participants with all other pre-existing ART regimens took placebo for CVC 150 mg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CVC 150 mg | Drug | Administered as one 150-mg tablet by mouth once a day with food. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel. | Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standardized Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR means a reduction in the target arterial wall inflammation over time. Index vessel is the vessel with the highest vessel TBR at baseline. The most diseased segment is the approximately 1-cm section of the vessel with the highest activity at baseline. The results are expressed as the ratio of TBR at week 24 to baseline. For the statistical analyses, results for the 6 and 9 missing values in Arm A and Arm B, respectively, were imputed using multiple imputation by regression. | Measured at baseline and week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs) | Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standard Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of TBR at week 24 to baseline. |
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Key Inclusion Criteria:
Documented to be living with HIV-1 infection.
Currently on a stable, continuous NNRTI-based or unboosted INSTI-based ART regimen for ≥48 weeks prior to study entry with no plans to change ART during the course of the study.
At least a year of controlled HIV-1 RNA levels.
Current CD4+ cell count >200 cells/mm^3.
Elevated cardiovascular risk defined as at least one of the following:
Key Exclusion Criteria:
Acute coronary syndrome
A current diagnosis of latent or active tuberculosis (TB) infection
Current diagnosis with other intracellular pathogens (Mycobacterium avium complex, Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans).
Untreated hepatitis B virus (HBV) infection
Current hepatitis C virus (HCV) infection
Current, acute or clinically significant infection or illness requiring IV antibiotics or hospitalization
History of cirrhosis with severe hepatic impairment and/or hepatic decompensation
Active malignancy, except squamous cell skin cancer.
Hemoglobin A1c >8% within 90 days prior to study entry.
Initiation of statin therapy or change in statin dose within 90 days prior to study entry.
Current use of any of the statins at the doses indicated:
Concurrent use of drugs with potential drug-drug interactions with CVC within 90 days prior to study entry.
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| Name | Affiliation | Role |
|---|---|---|
| Janet Lo, MD, MMSc | Massachusetts General Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Los Angeles CARE Center CRS (Site # 601) | Los Angeles | California | 90035 | United States | ||
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| Label | URL |
|---|---|
| Specific table used in the study protocol. For example, "The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009)." | View source |
| Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010 | View source |
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Results will be published in a manuscript and supporting information submitted to NHLBI BioData Catalyst® (BDC) (including data dictionaries and case report forms).
Within 3 years of final participant follow-up.
Data will be available by request in the NHLBI repository.
Participants were randomized 2:1 to CVC arm (Arm A) or placebo for CVC arm (Arm B) and stratified by statin use status (current statin use or no current statin use) at study entry (enrollment).
110 participants were enrolled from 19 US clinical research sites between May 30, 2023 and January 5, 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | CVC Arm (Arm A) | Participants with pre-existing ART regimen of EFV took CVC 300 mg. Participants with all other pre-existing ART regimens took CVC 150 mg. CVC 150 mg: Administered as one 150-mg tablet by mouth once a day with food. CVC 300 mg: Administered as two 150-mg tablets by mouth once a day with food. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Study Completion |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form: Protocol Version 2.0 | Mar 22, 2024 |
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At study entry, participants were randomized 2:1 to oral CVC (Arm A) or oral placebo for CVC (Arm B) once a day. The study treatment was added to the participants' pre-existing antiretroviral treatment (ART) regimens.
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| CVC 300 mg |
| Drug |
Administered as two 150-mg tablets by mouth once a day with food. |
|
| Placebo for CVC 150 mg | Other | Administered as one 150-mg matching placebo tablets by mouth once a day with food. |
|
| Placebo for CVC 300 mg | Other | Administered as two 150-mg matching placebo tablets by mouth once a day with food. |
|
| Measured at baseline and week 24 |
| Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta | Standard Uptake Value (SUV) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid). Specifically, it is the average of all evaluable SUV for a given arterial vessel. A negative number for the change in SUV implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of SUV at week 24 to baseline. | Measured at baseline and week 24 |
| Change in Fasting Glucose | Fasting glucose (mg/dL) measures the level of sugar (glucose) in the blood after fasting (no eating or drinking except water) for at least 8 hours. Higher value of change means an increase in glucose levels over time. The results are expressed as the change in fasting glucose from baseline to week 24. | Measured at baseline and week 24 |
| Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | Insulin is a hormone crucial in regulating blood sugar levels. HOMA-IR is a calculation used to assess insulin resistance and is calculated with the formula: insulin (uIU/mL) * glucose (mg/dL) / 405. Higher value of change in insulin and HOMA-IR means an increase in insulin resistance over time. The results are expressed as the ratio of fasting insulin or HOMA-IR at week 24 to baseline. | Measured at baseline and week 24 |
| Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | The cytokine, Interleukin-6 (IL-6, pg/mL); protein, high-sensitivity C Reactive Protein (hsCRP, mg/L); and chemokine, monocyte chemoattractant protein-1 (MCP-1, pg/mL) are all markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. MCP-1 is a ligand of CCR2 that was expected to increase with CVC. The results are expressed as the ratio of hsCRP, IL-6, or MCP-1 at week 24 to baseline. | Measured at baseline and week 24 |
| Change in Biomarkers of Immune Activation (sCD14 and sCD163) | The soluble proteins soluble-CD14 (sCD14, ng/mL) and soluble-CD163 (sCD163, ng/mL) are all markers of monocyte/macrophage activation. Higher value of change means an increase in the biomarker levels over time. Higher levels of sCD14 and sCD163 occur in response to inflammation and infection. The results are expressed as the difference between sCD14 or sCD163 from baseline to week 24. | Measured at baseline and week 24 |
| Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta) | The chemokines macrophage inflammatory protein-1 alpha and beta (MIP-1 alpha and beta, pg/mL) as well as the chemokine, RANTES (ng/mL), are markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. RANTES and MIP-1 beta are ligands of CCR5 that were expected to increase with CVC. The results are expressed as the ratio of RANTES or MIP-1 beta at week 24 to baseline. | Measured at baseline and week 24 |
| UCSD Antiviral Research Center CRS (Site # 701) |
| San Diego |
| California |
| 92103 |
| United States |
| UCSF HIV/AIDS CRS (Site # 801) | San Francisco | California | 94110 | United States |
| Harbor University of California Los Angeles Center CRS (Site # 603) | Torrance | California | 90502 | United States |
| Northwestern University CRS (Site # 2701) | Chicago | Illinois | 60611 | United States |
| Massachusetts General Hospital CRS (MGH CRS) (Site # 101) | Boston | Massachusetts | 02114 | United States |
| Brigham and Women's Hospital Therapeutics (BWH TCRS) CRS (Site # 107) | Boston | Massachusetts | 02115 | United States |
| Washington University Therapeutics (WT) CRS (Site # 2101) | St Louis | Missouri | 63110-1010 | United States |
| Weill Cornell Chelsea CRS (Site # 7804) | New York | New York | 10010 | United States |
| Weill Cornell Uptown CRS (Site # 7803) | New York | New York | 10065 | United States |
| University of Rochester Adult HIV Therapeutic Strategies Network CRS (Site # 31787) | Rochester | New York | 14642 | United States |
| Chapel Hill CRS (Site # 3201) | Chapel Hill | North Carolina | 27599-7215 | United States |
| Cincinnati CRS (Site # 2401) | Cincinnati | Ohio | 45267-0405 | United States |
| Case CRS (Site # 2501) | Cleveland | Ohio | 44106 | United States |
| Ohio State University CRS (Site # 2301) | Columbus | Ohio | 43210-1282 | United States |
| University of Pittsburgh CRS (Site # 1001) | Pittsburgh | Pennsylvania | 15213 | United States |
| Vanderbilt Therapeutics (VT) CRS (Site # 3652) | Nashville | Tennessee | 37204 | United States |
| Houston AIDS Research Team CRS (Site # 31473) | Houston | Texas | 77030 | United States |
| University of Washington Positive Research CRS (Site # 1401) | Seattle | Washington | 98104 | United States |
| Placebo for CVC Arm (Arm B) |
Participants with pre-existing ART regimen of EFV took placebo for CVC 300 mg. Participants with all other pre-existing ART regimens took placebo for CVC 150 mg. Placebo for CVC 150 mg: Administered as one 150-mg matching placebo tablets by mouth once a day with food. Placebo for CVC 300 mg: Administered as two 150-mg matching placebo tablets by mouth once a day with food. |
| COMPLETED | Participants who have been in the study for at least 22 weeks are considered to have completed the study. |
|
| NOT COMPLETED |
|
|
| Efficacy Analysis Population Set |
|
|
Population is based on enrolled participants who initiated study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | CVC Arm (Arm A) | Participants with pre-existing ART regimen of EFV took CVC 300 mg. Participants with all other pre-existing ART regimens took CVC 150 mg. CVC 150 mg: Administered as one 150-mg tablet by mouth once a day with food. CVC 300 mg: Administered as two 150-mg tablets by mouth once a day with food. |
| BG001 | Placebo for CVC Arm (Arm B) | Participants with pre-existing ART regimen of EFV took placebo for CVC 300 mg. Participants with all other pre-existing ART regimens took placebo for CVC 150 mg. Placebo for CVC 150 mg: Administered as one 150-mg matching placebo tablets by mouth once a day with food. Placebo for CVC 300 mg: Administered as two 150-mg matching placebo tablets by mouth once a day with food. |
| 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 | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Gender Identity | Count of Participants | Participants |
| ||||||||||||||||
| Body Mass Index (BMI) | Median | Inter-Quartile Range | kg/m^2 |
| |||||||||||||||
| BMI Groups | Count of Participants | Participants |
| ||||||||||||||||
| Estimated Glomerular Filtration Rate (eGFR) | Estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation. | Median | Inter-Quartile Range | mL/min/1.73m^2 |
| ||||||||||||||
| eGFR Groups | Estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation. | Count of Participants | Participants |
| |||||||||||||||
| CD4 Count | Median | Inter-Quartile Range | cells/mm^3 |
| |||||||||||||||
| CD4 Percent | Median | Inter-Quartile Range | % |
| |||||||||||||||
| HIV-1 RNA | HIV-1 RNA levels were quantified at Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory using an ultrasensitive viral load (VL) assay. Assays with lower limit of quantification (LLQ) of 20, 30, 40, and 50 copies/mL were reported. | Count of Participants | Participants |
| |||||||||||||||
| Antiretroviral Therapy (ART) Class | Count of Participants | Participants |
| ||||||||||||||||
| Count of High-Risk Cardiovascular Risk Factors | Count of Participants | Participants |
| ||||||||||||||||
| Statin-use at Entry | Count of Participants | Participants |
| ||||||||||||||||
| Index Vessel | Index vessel is the most inflamed vessel (highest target vessel target-to-background ratio (TBR) between aorta, left, or right carotid) at study entry. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Count of Participants | Participants |
| ||||||||||||||
| Index Vessel Most-Diseased Segment (MDS) Target-to-Background Ratio (TBR) | Index vessel MDS TBR is the most-diseased (inflamed) segment of the index vessel. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | Ratio |
| |||||||||||||
| Aorta Vessel TBR | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | Ratio |
| ||||||||||||||
| Left Carotid Artery Vessel TBR | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | Ratio |
| ||||||||||||||
| Right Carotid Artery Vessel TBR | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | Ratio |
| ||||||||||||||
| Bilateral Carotid Arteries Vessel TBR | Obtained by averaging the right carotid and left carotid artery vessel TBR for a given participant. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | Ratio |
| |||||||||||||
| Aorta Vessel Standard Uptake Value (SUV) | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | SUV |
| ||||||||||||||
| Bilateral Carotid Arteries Vessel SUV | Obtained by averaging the right carotid and left carotid artery vessel SUV for a given participant. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | SUV |
| |||||||||||||
| C-Reactive Protein (hsCRP) | Measured using high-sensitivity CRP (hsCRP) test to detect smaller changes in CRP levels. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | mg/L |
| |||||||||||||
| Interleukin-6 | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | pg/mL |
| ||||||||||||||
| Soluble CD14 | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | ng/mL |
| ||||||||||||||
| Soluble CD163 | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | ng/mL |
| ||||||||||||||
| MCP-1 | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | pg/mL |
| ||||||||||||||
| MIP-1 alpha | Assay lower limit of quantification (LLQ) is 46.9 pg/mL. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Count of Participants | Participants |
| ||||||||||||||
| MIP-1 beta | Assay lower limit of quantification (LLQ) is 31.3 pg/mL. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Count of Participants | Participants |
| ||||||||||||||
| MIP-1 beta | Records below LLQ are imputed as half of LLQ. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | pg/mL |
| |||||||||||||
| RANTES | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | ng/mL |
| ||||||||||||||
| Fasting Glucose | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | mg/dL |
| ||||||||||||||
| Fasting Insulin | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | uIU/mL |
| ||||||||||||||
| Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | HOMA-IR is a calculation used to assess insulin resistance and is calculated with the formula: insulin (uIU/mL) * glucose (mg/dL) / 405. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Median | Inter-Quartile Range | HOMA-IR Index |
|
| 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 | Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel. | Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standardized Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR means a reduction in the target arterial wall inflammation over time. Index vessel is the vessel with the highest vessel TBR at baseline. The most diseased segment is the approximately 1-cm section of the vessel with the highest activity at baseline. The results are expressed as the ratio of TBR at week 24 to baseline. For the statistical analyses, results for the 6 and 9 missing values in Arm A and Arm B, respectively, were imputed using multiple imputation by regression. | Efficacy population: all enrolled participants who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Posted | Median | Inter-Quartile Range | Fold-change | Measured at baseline and week 24 |
|
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs) | Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standard Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of TBR at week 24 to baseline. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Posted | Median | Inter-Quartile Range | Fold-change | Measured at baseline and week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta | Standard Uptake Value (SUV) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid). Specifically, it is the average of all evaluable SUV for a given arterial vessel. A negative number for the change in SUV implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of SUV at week 24 to baseline. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Posted | Median | Inter-Quartile Range | Fold-change | Measured at baseline and week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Fasting Glucose | Fasting glucose (mg/dL) measures the level of sugar (glucose) in the blood after fasting (no eating or drinking except water) for at least 8 hours. Higher value of change means an increase in glucose levels over time. The results are expressed as the change in fasting glucose from baseline to week 24. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Posted | Median | Inter-Quartile Range | mg/dL | Measured at baseline and week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | Insulin is a hormone crucial in regulating blood sugar levels. HOMA-IR is a calculation used to assess insulin resistance and is calculated with the formula: insulin (uIU/mL) * glucose (mg/dL) / 405. Higher value of change in insulin and HOMA-IR means an increase in insulin resistance over time. The results are expressed as the ratio of fasting insulin or HOMA-IR at week 24 to baseline. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Posted | Median | Inter-Quartile Range | Fold-change | Measured at baseline and week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | The cytokine, Interleukin-6 (IL-6, pg/mL); protein, high-sensitivity C Reactive Protein (hsCRP, mg/L); and chemokine, monocyte chemoattractant protein-1 (MCP-1, pg/mL) are all markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. MCP-1 is a ligand of CCR2 that was expected to increase with CVC. The results are expressed as the ratio of hsCRP, IL-6, or MCP-1 at week 24 to baseline. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Posted | Median | Inter-Quartile Range | Fold-change | Measured at baseline and week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Biomarkers of Immune Activation (sCD14 and sCD163) | The soluble proteins soluble-CD14 (sCD14, ng/mL) and soluble-CD163 (sCD163, ng/mL) are all markers of monocyte/macrophage activation. Higher value of change means an increase in the biomarker levels over time. Higher levels of sCD14 and sCD163 occur in response to inflammation and infection. The results are expressed as the difference between sCD14 or sCD163 from baseline to week 24. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Posted | Median | Inter-Quartile Range | ng/mL | Measured at baseline and week 24 |
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| Secondary | Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta) | The chemokines macrophage inflammatory protein-1 alpha and beta (MIP-1 alpha and beta, pg/mL) as well as the chemokine, RANTES (ng/mL), are markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. RANTES and MIP-1 beta are ligands of CCR5 that were expected to increase with CVC. The results are expressed as the ratio of RANTES or MIP-1 beta at week 24 to baseline. | Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. | Posted | Median | Inter-Quartile Range | Fold-change | Measured at baseline and week 24 |
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From study entry to completion at Week 24 or premature study discontinuation.
All adverse events (AE) that met reporting criteria as defined in Protocol v2.0 Section 7.2 were collected. The DAIDS AE Grading Table (v2.1) was used. All eligible participants who initiated study treatment are included.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CVC Arm (Arm A) | Participants with pre-existing ART regimen of EFV took CVC 300 mg. Participants with all other pre-existing ART regimens took CVC 150 mg. CVC 150 mg: Administered as one 150-mg tablet by mouth once a day with food. CVC 300 mg: Administered as two 150-mg tablets by mouth once a day with food. | 0 | 74 | 4 | 74 | 44 | 74 |
| EG001 | Placebo for CVC Arm (Arm B) | Participants with pre-existing ART regimen of EFV took placebo for CVC 300 mg. Participants with all other pre-existing ART regimens took placebo for CVC 150 mg. Placebo for CVC 150 mg: Administered as one 150-mg matching placebo tablets by mouth once a day with food. Placebo for CVC 300 mg: Administered as two 150-mg matching placebo tablets by mouth once a day with food. | 0 | 36 | 2 | 36 | 20 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Respiratory tract infection viral | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Blood triglycerides increased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
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| Myelopathy | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
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| Intentional self-injury | Psychiatric disorders | MedDRA 27.1 | Systematic Assessment |
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| Urinary retention | Renal and urinary disorders | MedDRA 27.1 | Systematic Assessment |
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| Priapism | Reproductive system and breast disorders | MedDRA 27.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 27.1 | Systematic Assessment |
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| Anal fissure | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 27.1 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Onychomycosis | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Oropharyngeal gonococcal infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Paronychia | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
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| Immunisation reaction | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
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| Amylase increased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Blood cholesterol increased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Blood creatinine decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Blood glucose decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Blood glucose increased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Blood sodium increased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Blood triglycerides increased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Creatinine renal clearance decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Glomerular filtration rate decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Low density lipoprotein increased | Investigations | MedDRA 27.1 | Systematic Assessment |
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| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
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| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
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| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
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| Cervical radiculopathy | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
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| Drug abuse | Psychiatric disorders | MedDRA 27.1 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA 27.1 | Systematic Assessment |
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| Endometrial hyperplasia | Reproductive system and breast disorders | MedDRA 27.1 | Systematic Assessment |
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| Uterine polyp | Reproductive system and breast disorders | MedDRA 27.1 | Systematic Assessment |
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| Obstructive sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 27.1 | Systematic Assessment |
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In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| ACTG Clinicaltrials.gov Coordinator | ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company | (301) 628-3348 | ACTGCT.gov@fstrf.org |
| Mar 7, 2025 |
| Prot_ICF_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 18, 2024 | Apr 28, 2025 | SAP_001.pdf |
Not provided
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Estimate obtained from regression on log10-transformed scale was back-transformed to the original scale and rounded to 3 decimal places. It reflects the relative geometric mean fold-change in the TBR from baseline for CVC compared to placebo.
| Superiority |
| Evaluates whether CVC, compared to placebo, changes arterial inflammation in the MDS of the index vessel differently by statin-use at study entry (use versus no-use). | Regression, Linear | Outcome was log10-transformed. Model adjusted for statin-use and its interaction with treatment. Analysis used multiple imputation for missing data. | 0.40 | P-value for modification of the CVC treatment effect by subgroups defined by statin-use is presented. A-priori threshold for statistical significance is at p < 0.05. No adjustments for multiple comparisons were done. | Other | Statistical test for interaction. |
| Evaluates whether CVC, compared to placebo, changes arterial inflammation in the MDS of the index vessel differently by sex (female versus male). | Regression, Linear | Outcome was log10-transformed. Model adjusted for sex (F vs M) and its interaction with treatment. Analysis used multiple imputation for missing data. | 0.63 | P-value for modification of the CVC treatment effect by subgroups defined by sex is presented. A-priori threshold for statistical significance is at p < 0.05. No adjustments for multiple comparisons were done. | Other | Statistical test for interaction. |
| Evaluates whether CVC, compared to placebo, changes arterial inflammation in the MDS of the index vessel differently by race (Black/African-American versus Non-Black/African-American). | Regression, Linear | Outcome was log10-transformed. Model adjusted for race and its interaction with treatment. Analysis used multiple imputation for missing data. | 0.71 | P-value for modification of the CVC treatment effect by subgroups defined by race is presented. A-priori threshold for statistical significance is at p < 0.05. No adjustments for multiple comparisons were done. | Other | Statistical test for interaction. |
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