Dyslipidemias, HIV Infections
Conditions
Keywords
HIV Dyslipidemias, CD24Fc, HIV Chronic Inflammation, LDL Reduction
Brief summary
This is a phase 2, randomized, double-blinded, placebo-controlled clinical trial. The intervention drug will be efprezimod alfa (intravenous \[IV\] infusion). A cohort of 64 patients with HIV on antiretroviral therapy (ART) will be randomized in a 1:1 fashion to be administered 3 doses of efprezimod alfa (240mg IV infusion) or placebo once every 2 weeks (q2w) during a 4-week window, followed by a 24-week follow-up window to assess the changes in LDL.
Detailed description
This study is a phase 2, randomized, placebo-control, double-blinded clinical trial to assess the effect of efprezimod alfa on reduction in low-density lipoprotein (LDL) among patients with HIV. The effect of efprezimod alfa on total cholesterol and triglycerides, markers of immune activation (T cell activation, sCD14, and inflammatory cytokines), size of HIV reservoirs, hemoglobin (HbA1c) and leptin, and hepatic steatosis will be evaluated. It is hypothesized that therapy with efprezimod alfa will result in significant decreases in LDL in HIV patients. In addition, efprezimod alfa may reduce leptin and cholesterol, HbA1c, hepatic steatosis and fibrosis, and markers of inflammation in patients with chronic HIV who are virally suppressed on ART. In this phase 2 study, a cohort of 64 HIV patients virally suppressed on ART will be randomized in a 1:1 fashion to receive an intravenous infusion of 240 mg of efprezimod alfa vs. placebo administered every 2 weeks during a 4-week treatment window, followed by a 24- week follow-up period. Patients will be followed for safety and adverse events as well as changes in lipid metabolism and inflammatory markers during a 24-week follow-up period. This investigation will take place at the University of Maryland.
Interventions
DRUGEfprezimod alfa (human CD24 extracellular domain and human IgG1 Fc fusion protein)
Efprezimod alfa will be given as IV infusion, 240 mg per infusion, on Days 0, 14, and 28.
DRUGSaline Solution
Sterile saline solution (0.9% sodium chloride) will be given as placebo via IV infusion, 100 ml per infusion, on Days 0, 14, and 28.
Sponsors
University of Maryland, Baltimore
Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Randomized, double blinded, placebo controlled.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provides signed and dated informed consent form * Is willing to comply with all study procedures and availability for the duration of the study * Is at least 50 years of age or older at screening * Has LDL-C \> 70 mg/dL. * Has a median American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) ACC/AHA ASCVD risk score ≥ 7.5%. * Is available for clinical follow-up through Week 28 after enrollment. * Has chronic HIV infection based on documentation from a primary care physician that the participant has HIV and is on antiretroviral therapy (ART). * Is on a stable regimen of ART. * Has at least 2 years of maintained HIV ribonucleic acid (RNA) \< 50 copies/mL (or \< lower limit of quantification \[LLOQ\] if the local laboratory assay's LLOQ is ≥50 copies/mL) prior to Screening and HIV RNA\<50 at screening. * Has CD4 cell count ≥350 cells/mm\^3 at Screening. * Is able to communicate effectively with the study investigator and other key personnel * Has a primary care doctor for their medical management * Is willing to donate blood for sample storage to be used for future research * Female study participants with childbearing potential (defined below) and male study participants with female partners of childbearing potential must be willing to practice either: * Complete abstinence from sexual intercourse with a member of the opposite sex OR * Uses at least one form of effective contraception, in addition to correct use of either a male or female condom throughout dosing and for a defined period following the last dose (30 days for women, 14 days for men) of study medication * Definition of Childbearing Potential: For the purposes of this study, a female subject is considered of childbearing potential from menarche until becoming post-menopausal, unless permanently sterile or with medically documented ovarian failure. Women are considered to be in a post-menopausal state when they are ≥ 54 years of age with cessation of previously occurring menses for ≥ 12 months without an alternative cause. Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral salpingectomy in a female subject of any age. * Agrees to adhere to Lifestyle Considerations throughout study duration
Exclusion criteria
* Has a current or prior history of any of the following: 1. Clinically significant illness (other than HIV) or any other major medical disorder that may, in the opinion of the investigator, interfere with the participant treatment, assessment of compliance with the protocol; participants currently under evaluation for a clinically-significant illness (other than HIV) are also excluded 2. Poor venous access interfering with required study blood collection 3. Solid organ transplantation 4. Significant pulmonary disease, significant cardiac disease, or porphyria 5. Uncontrolled chronic hepatitis B infection (surface antigen positive with detectable HBV DNA as noted in participant's medical documentation from a treating physician) 6. Chronic, current/active hepatitis C infection 7. Unstable psychiatric disease. (Subjects with psychiatric illness that is well-controlled on a stable treatment regimen or currently not requiring medication may be included.) 8. Any malignancy or its treatment that in the opinion of the Principal Investigator (PI) may cause ongoing interference with host immunity; subjects under evaluation for malignancy are not eligible. * Has abnormal hematological and biochemical parameters at screening, unless the test has been repeated and at least one subsequent result is within the acceptable range prior to study drug administration, including: 1. Neutrophil count \<750 cells/mm\^3 2. Hemoglobin level \<10 g/dL 3. Platelet count ≤50,000 cells/mm\^3 4. Estimated glomerular filtration rate, calculated by the chronic kidney disease epidemiology collaboration formula: \<30 mL/min/1.73 m\^2 5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥5 times upper limit of normal (ULN) 6. Total bilirubin level ≥2.0 times ULN, except in subjects with Gilbert's syndrome or other clinical explanation at the discretion of the PI 7. Albumin level \<3 g/dL * Has poorly controlled diabetes as indicated by a screening glycosylated hemoglobin (HbA1c) \>10 * Has need for the use of the following medications from 21 days prior to the start of study drugs through the end of treatment: 1. Hematologic stimulating agents, erythropoiesis stimulating agents (ESAs), granulocyte colony stimulating factor (GCSF), thrombopoeitin (TPO) mimetics 2. Chronic systemic antineoplastic or immunomodulatory treatment including supraphysiologic doses of immunosuppressants such as corticosteroids (e.g., prednisone equivalent \>10 mg/day for \>2 weeks), azathioprine or monoclonal antibodies (e.g., infliximab) 3. Investigational agents or devices for any indication * Has hyperlipidemia (defined as an LDL ≥190 mg/dL), that is not being treated with 2018 ACC/AHA Cholesterol Clinical Practice guidelines (statins, Ezetimibe, PCSK9 inhibitors) * Has a known history of cardiac arrhythmia or baseline ECG with arrhythmia including but not limited to atrial fibrillation (with or without rapid ventricular rate), supraventricular tachycardia or ventricular tachycardia. * Has any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent. * Is a female who is breast-feeding or planning to become pregnant during the first 24 weeks after study drug administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Withdrew From Study Treatment Due to an AE | Up to approximately 4 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any worsening of a preexisting condition which is temporally associated with the use of the study treatment is also considered an AE. The number of participants who withdrew from study treatment due to an AE is presented. |
| Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | Baseline and Week 6 | LDL-C was measured in participant serum. The percent change from baseline at Week 6 is presented. |
| Number of Participants With ≥1 Adverse Event (AE) | Up to approximately 28 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any worsening of a preexisting condition which is temporally associated with the use of the study treatment is also considered an AE. The number of participants who experienced an AE is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Tumor Necrosis Factor (TNF)+ Peripheral Blood Mononuclear Cells (PBMCs) | Baseline, Week 6, and Week 28 | The percent change from baseline in the percentage of PBMCs that were TNF+ at Weeks 6 and 28 was to be presented. |
| Percent Change From Baseline in Whole Blood Soluble Cluster of Differentiation 14 (sCD14) Concentration | Baseline, Week 6, and Week 28 | The percent change from baseline in sCD14 concentration in whole blood at Weeks 6 and 28 was to be presented. |
| Change From Baseline in Human Immunodeficiency Virus (HIV) Proviral Deoxyribonucleic Acid (DNA) | Baseline, Week 6, and Week 28 | Blood was collected at baseline, Week 6, and Week 28 for the determination of the number of copies of HIV proviral DNA in PBMCs. The change from baseline at Weeks 6 and 28 was to be presented. |
| Percent Change From Baseline in Troponin I and Troponin T Serum Levels | Baseline and Week 28 | Troponin I and troponin T blood concentrations were to be measured. The percent change from baseline at Week 28 was to be presented. |
| Percent Change From Baseline in Controlled Attenuation Parameter (CAP) as Determined by Transient Elastography of the Liver | Baseline and Week 28 | CAP is a measure related to hepatic steatosis. CAP was measured in decibels per meter (dB/m) at baseline and Week 28. The percent change is presented. |
| Percent Change From Baseline in Liver Stiffness as Determined by Transient Elastography of the Liver | Baseline and Week 28 | Liver stiffness is a measure related to hepatic fibrosis. Liver stiffness was measured in kilopascals (kPa) at baseline and Week 28. The percent change is presented. |
| Percent Change From Baseline in Leptin | Baseline, Week 6, and Week 28 | Leptin concentration was measured in participant serum. The percent change from baseline at Weeks 6 and 28 is presented. |
| Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Baseline, Week 6, and Week 28 | Total cholesterol, HDL-C, and triglycerides were measured in participant serum. The percent change from baseline at Weeks 6 and 28 for these lipid panel results is presented. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of CD24Fc | Predose and 2 hours postdose at the Week 0, 2, and 4 visits; Any time during the Week 6, 16, and 28 visits. | AUC was defined as the area of plasma concentration versus time curve from time zero to Week 28. Assessment of AUC was to be based on CD24Fc concentration measured in plasma samples collected at each study visit starting with Week 0. |
| Number of Participants With New Anti-Drug Antibodies | Baseline, Week 6, and Week 28 | Anti-CD24Fc antibodies were to be quantified in participant blood samples. The number of participants who demonstrated development of new anti-drug antibodies were to be presented. |
| Change From Baseline in Interluekin-6 (IL-6) Levels Following CD24Fc Treatment | Baseline and Week 28 | Levels of IL-6 were to be measured in participant blood samples collected at baseline and Week 28. The change from baseline in IL-6 levels were to be presented. |
| Change From Baseline in Apolipoprotein B (apoB) Levels | Baseline and Week 28 | Levels of apoB were measured in participant blood samples collected at baseline and Week 28. The change from baseline level is presented. |
| Change From Baseline in Lipoprotein(a) (Lp[a]) Levels | Baseline and Week 28 | Levels of Lp(a) were measured in participant blood samples collected at baseline and Week 28. The change from baseline level is presented. |
| Change From Baseline in Urine Albumin:Creatinine Ratio | Baseline and Week 28 | The ratio between levels of albumin and creatine was measured in participant urine at baseline and Week 28. The change from baseline in the ratio is presented. |
| Percent Change From Baseline in Glycated Hemoglobin (HbA1c) | Baseline, Week 6, and Week 28 | Glycated hemoglobin (HbA1c) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage HbA1c is the ratio of glycated hemoglobin to total hemoglobin x 100. The percent change from baseline at Weeks 6 and 28 is presented. |
| Percent Change From Baseline in Cluster of Differentiation 4 (CD4)+ and Cluster of Differentiation 8 (CD8)+ T Cell Percentage | Baseline, Week 6, and Week 28 | The percent change from baseline in the percentage of T Cells in whole blood that are CD4+ and CD8+ at Weeks 6 and 28 was to be presented. |
| Percent Change From Baseline in Interferon (IFN)+ Peripheral Blood Mononuclear Cells (PBMCs) | Baseline, Week 6, and Week 28 | The percent change from baseline in the percentage of PBMCs that were INF+ at Weeks 6 and 28 was to be presented. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Aortic F-fluorodeoxyglucose (FDG) Uptake | Baseline and Week 24 | Arterial FDG uptake is used to evaluate arterial inflammation. Arterial FDG uptake was to be measured by positron emission tomography-computed tomography (PET/CT) scan at Baseline and Week 24 in the aortic root and the same superior vena cava, then reported as the aortic uptake value divided by the superior vena cava uptake value, the target-to-background ratio (TBR). The change from baseline at Week 24 was to be presented. |
Countries
United States
Participant flow
Recruitment details
8 participants were randomized at 1 study site in the United States.
Participants by arm
| Arm | Count |
|---|---|
| CD24Fc 240 mg Participants received an intravenous infusion of 240 mg of CD24Fc on Days 0, 14, and 28. | 4 |
| Placebo Participants received an intravenous infusion of placebo (sterile saline solution) on Days 0, 14, and 28. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Total | Placebo | CD24Fc 240 mg |
|---|---|---|---|
| Age, Continuous | 55.6 Years STANDARD_DEVIATION 6.09 | 58.8 Years STANDARD_DEVIATION 7.59 | 52.5 Years STANDARD_DEVIATION 1.73 |
| Controlled Attenuation Parameter (CAP) | 226.5 Decibels/meter (dB/m) STANDARD_DEVIATION 78.3 | 215.5 Decibels/meter (dB/m) STANDARD_DEVIATION 27.26 | 237.5 Decibels/meter (dB/m) STANDARD_DEVIATION 115.07 |
| Liver Stiffness | 5.53 Kilopascal (kPa) STANDARD_DEVIATION 2.462 | 5.40 Kilopascal (kPa) STANDARD_DEVIATION 1.699 | 5.65 Kilopascal (kPa) STANDARD_DEVIATION 3.348 |
| Low-Density Lipoprotein-Cholesterol (LDL-C) | 112.4 mg/dL STANDARD_DEVIATION 33.72 | 116.0 mg/dL STANDARD_DEVIATION 46.01 | 108.8 mg/dL STANDARD_DEVIATION 22.38 |
| Percent Glycated Hemoglobin (HbA1c) | 5.76 Percentage of Hemoglobin STANDARD_DEVIATION 0.655 | 5.55 Percentage of Hemoglobin STANDARD_DEVIATION 0.191 | 5.98 Percentage of Hemoglobin STANDARD_DEVIATION 0.918 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Serum High-Density Lipoprotein-Cholesterol (HDL-C) | 50.6 mg/dL STANDARD_DEVIATION 14.58 | 49.3 mg/dL STANDARD_DEVIATION 8.18 | 52.0 mg/dL STANDARD_DEVIATION 20.59 |
| Serum Leptin | 23.14 µg/L STANDARD_DEVIATION 27.322 | 18.63 µg/L STANDARD_DEVIATION 30.388 | 27.65 µg/L STANDARD_DEVIATION 27.641 |
| Serum Total Cholesterol | 186.3 mg/dL STANDARD_DEVIATION 40.96 | 190.0 mg/dL STANDARD_DEVIATION 47.57 | 182.5 mg/dL STANDARD_DEVIATION 40.17 |
| Serum Triglycerides | 131.6 mg/dL STANDARD_DEVIATION 55.36 | 141.8 mg/dL STANDARD_DEVIATION 68.01 | 121.5 mg/dL STANDARD_DEVIATION 47.47 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
Number of Participants Who Withdrew From Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any worsening of a preexisting condition which is temporally associated with the use of the study treatment is also considered an AE. The number of participants who withdrew from study treatment due to an AE is presented.
Time frame: Up to approximately 4 weeks
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CD24Fc 240 mg | Number of Participants Who Withdrew From Study Treatment Due to an AE | 0 Participants |
| Placebo | Number of Participants Who Withdrew From Study Treatment Due to an AE | 0 Participants |
Primary
Number of Participants With ≥1 Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any worsening of a preexisting condition which is temporally associated with the use of the study treatment is also considered an AE. The number of participants who experienced an AE is presented.
Time frame: Up to approximately 28 weeks
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CD24Fc 240 mg | Number of Participants With ≥1 Adverse Event (AE) | 4 Participants |
| Placebo | Number of Participants With ≥1 Adverse Event (AE) | 4 Participants |
Primary
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C)
LDL-C was measured in participant serum. The percent change from baseline at Week 6 is presented.
Time frame: Baseline and Week 6
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CD24Fc 240 mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | 6.24 Percent Change | Standard Deviation 6.392 |
| Placebo | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | 6.51 Percent Change | Standard Deviation 19.69 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of CD24Fc
AUC was defined as the area of plasma concentration versus time curve from time zero to Week 28. Assessment of AUC was to be based on CD24Fc concentration measured in plasma samples collected at each study visit starting with Week 0.
Time frame: Predose and 2 hours postdose at the Week 0, 2, and 4 visits; Any time during the Week 6, 16, and 28 visits.
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. The estimated time to set up new validated assays exceeds the known stability of collected samples; therefore the samples will not be analyzed. Therefore, no participants were analyzed.
Secondary
Change From Baseline in Apolipoprotein B (apoB) Levels
Levels of apoB were measured in participant blood samples collected at baseline and Week 28. The change from baseline level is presented.
Time frame: Baseline and Week 28
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD24Fc 240 mg | Change From Baseline in Apolipoprotein B (apoB) Levels | Baseline | 109.0 mg/dL | Standard Deviation 19.34 |
| CD24Fc 240 mg | Change From Baseline in Apolipoprotein B (apoB) Levels | Change from Baseline | -9.8 mg/dL | Standard Deviation 14.75 |
| Placebo | Change From Baseline in Apolipoprotein B (apoB) Levels | Baseline | 105.0 mg/dL | Standard Deviation 29.31 |
| Placebo | Change From Baseline in Apolipoprotein B (apoB) Levels | Change from Baseline | 6.5 mg/dL | Standard Deviation 25.09 |
Secondary
Change From Baseline in Human Immunodeficiency Virus (HIV) Proviral Deoxyribonucleic Acid (DNA)
Blood was collected at baseline, Week 6, and Week 28 for the determination of the number of copies of HIV proviral DNA in PBMCs. The change from baseline at Weeks 6 and 28 was to be presented.
Time frame: Baseline, Week 6, and Week 28
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. Data for this outcome measure could not be collected because the laboratory was unable to run the assay. Therefore, no participants were analyzed.
Secondary
Change From Baseline in Interluekin-6 (IL-6) Levels Following CD24Fc Treatment
Levels of IL-6 were to be measured in participant blood samples collected at baseline and Week 28. The change from baseline in IL-6 levels were to be presented.
Time frame: Baseline and Week 28
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. No samples were collected for Week 28, so the change from baseline analysis could not be performed and no participants were analyzed.
Secondary
Change From Baseline in Lipoprotein(a) (Lp[a]) Levels
Levels of Lp(a) were measured in participant blood samples collected at baseline and Week 28. The change from baseline level is presented.
Time frame: Baseline and Week 28
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD24Fc 240 mg | Change From Baseline in Lipoprotein(a) (Lp[a]) Levels | Baseline | 60.38 mg/dL | Standard Deviation 39.443 |
| CD24Fc 240 mg | Change From Baseline in Lipoprotein(a) (Lp[a]) Levels | Change from Baseline | -15.03 mg/dL | Standard Deviation 9.662 |
| Placebo | Change From Baseline in Lipoprotein(a) (Lp[a]) Levels | Baseline | 301.45 mg/dL | Standard Deviation 140.645 |
| Placebo | Change From Baseline in Lipoprotein(a) (Lp[a]) Levels | Change from Baseline | 8.40 mg/dL | Standard Deviation 70.528 |
Secondary
Change From Baseline in Urine Albumin:Creatinine Ratio
The ratio between levels of albumin and creatine was measured in participant urine at baseline and Week 28. The change from baseline in the ratio is presented.
Time frame: Baseline and Week 28
Population: All randomized participants who received ≥1 dose of study drug and had data available for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD24Fc 240 mg | Change From Baseline in Urine Albumin:Creatinine Ratio | Baseline | 6.0 Ratio (g Albumin/mol Creatinine) | Standard Deviation 2.65 |
| CD24Fc 240 mg | Change From Baseline in Urine Albumin:Creatinine Ratio | Change from Baseline | 0.5 Ratio (g Albumin/mol Creatinine) | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio | Baseline | 796.3 Ratio (g Albumin/mol Creatinine) | Standard Deviation 1322.45 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio | Change from Baseline | -357.0 Ratio (g Albumin/mol Creatinine) | Standard Deviation 434.16 |
Secondary
Number of Participants With New Anti-Drug Antibodies
Anti-CD24Fc antibodies were to be quantified in participant blood samples. The number of participants who demonstrated development of new anti-drug antibodies were to be presented.
Time frame: Baseline, Week 6, and Week 28
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. The estimated time to set up new validated assays exceeds the known stability of collected samples; therefore the samples will not be analyzed. Therefore, no participants were analyzed.
Secondary
Percent Change From Baseline in Cluster of Differentiation 4 (CD4)+ and Cluster of Differentiation 8 (CD8)+ T Cell Percentage
The percent change from baseline in the percentage of T Cells in whole blood that are CD4+ and CD8+ at Weeks 6 and 28 was to be presented.
Time frame: Baseline, Week 6, and Week 28
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. Data for this outcome measure could not be collected because the laboratory was unable to run the assay. Therefore, no participants were analyzed.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Percent Change From Baseline in Cluster of Differentiation 4 (CD4)+ and Cluster of Differentiation 8 (CD8)+ T Cell Percentage | Percent Change from Baseline in CD4+ T Cell Percentage at Week 6 | — |
| Unknown | Percent Change From Baseline in Cluster of Differentiation 4 (CD4)+ and Cluster of Differentiation 8 (CD8)+ T Cell Percentage | Percent Change from Baseline in CD4+ T Cell Percentage at Week 28 | — |
| Unknown | Percent Change From Baseline in Cluster of Differentiation 4 (CD4)+ and Cluster of Differentiation 8 (CD8)+ T Cell Percentage | Percent Change from Baseline in CD8+ T Cell Percentage at Week 6 | — |
| Unknown | Percent Change From Baseline in Cluster of Differentiation 4 (CD4)+ and Cluster of Differentiation 8 (CD8)+ T Cell Percentage | Percent Change from Baseline in CD8+ T Cell Percentage at Week 28 | — |
Secondary
Percent Change From Baseline in Controlled Attenuation Parameter (CAP) as Determined by Transient Elastography of the Liver
CAP is a measure related to hepatic steatosis. CAP was measured in decibels per meter (dB/m) at baseline and Week 28. The percent change is presented.
Time frame: Baseline and Week 28
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CD24Fc 240 mg | Percent Change From Baseline in Controlled Attenuation Parameter (CAP) as Determined by Transient Elastography of the Liver | 23.98 Percent Change | Standard Deviation 34.167 |
| Placebo | Percent Change From Baseline in Controlled Attenuation Parameter (CAP) as Determined by Transient Elastography of the Liver | -5.86 Percent Change | Standard Deviation 33.756 |
Secondary
Percent Change From Baseline in Glycated Hemoglobin (HbA1c)
Glycated hemoglobin (HbA1c) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage HbA1c is the ratio of glycated hemoglobin to total hemoglobin x 100. The percent change from baseline at Weeks 6 and 28 is presented.
Time frame: Baseline, Week 6, and Week 28
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD24Fc 240 mg | Percent Change From Baseline in Glycated Hemoglobin (HbA1c) | Percent Change from Baseline at Week 6 | 0.69 Percent Change | Standard Deviation 3.665 |
| CD24Fc 240 mg | Percent Change From Baseline in Glycated Hemoglobin (HbA1c) | Percent Change from Baseline at Week 28 | 4.65 Percent Change | Standard Deviation 2.585 |
| Placebo | Percent Change From Baseline in Glycated Hemoglobin (HbA1c) | Percent Change from Baseline at Week 6 | -2.71 Percent Change | Standard Deviation 1.07 |
| Placebo | Percent Change From Baseline in Glycated Hemoglobin (HbA1c) | Percent Change from Baseline at Week 28 | 0.03 Percent Change | Standard Deviation 2.557 |
Secondary
Percent Change From Baseline in Interferon (IFN)+ Peripheral Blood Mononuclear Cells (PBMCs)
The percent change from baseline in the percentage of PBMCs that were INF+ at Weeks 6 and 28 was to be presented.
Time frame: Baseline, Week 6, and Week 28
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. Data for this outcome measure could not be collected because the laboratory was unable to run the assay. Therefore, no participants were analyzed.
Secondary
Percent Change From Baseline in Leptin
Leptin concentration was measured in participant serum. The percent change from baseline at Weeks 6 and 28 is presented.
Time frame: Baseline, Week 6, and Week 28
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD24Fc 240 mg | Percent Change From Baseline in Leptin | Percent Change from Baseline at Week 28 | 83.03 Percent Change | Standard Deviation 117.848 |
| CD24Fc 240 mg | Percent Change From Baseline in Leptin | Percent Change from Baseline at Week 6 | 46.72 Percent Change | Standard Deviation 36.104 |
| Placebo | Percent Change From Baseline in Leptin | Percent Change from Baseline at Week 28 | 29.84 Percent Change | Standard Deviation 84.316 |
| Placebo | Percent Change From Baseline in Leptin | Percent Change from Baseline at Week 6 | 22.43 Percent Change | Standard Deviation 73.205 |
Secondary
Percent Change From Baseline in Liver Stiffness as Determined by Transient Elastography of the Liver
Liver stiffness is a measure related to hepatic fibrosis. Liver stiffness was measured in kilopascals (kPa) at baseline and Week 28. The percent change is presented.
Time frame: Baseline and Week 28
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CD24Fc 240 mg | Percent Change From Baseline in Liver Stiffness as Determined by Transient Elastography of the Liver | -0.81 Percent Change | Standard Deviation 52.168 |
| Placebo | Percent Change From Baseline in Liver Stiffness as Determined by Transient Elastography of the Liver | 16.16 Percent Change | Standard Deviation 27.449 |
Secondary
Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides
Total cholesterol, HDL-C, and triglycerides were measured in participant serum. The percent change from baseline at Weeks 6 and 28 for these lipid panel results is presented.
Time frame: Baseline, Week 6, and Week 28
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD24Fc 240 mg | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in Total Cholesterol at Week 6 | 4.66 Percent Change | Standard Deviation 5.85 |
| CD24Fc 240 mg | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in HDL-C at Week 6 | 6.69 Percent Change | Standard Deviation 12.25 |
| CD24Fc 240 mg | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in Triglycerides at Week 6 | -8.42 Percent Change | Standard Deviation 24.982 |
| CD24Fc 240 mg | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in Total Cholesterol at Week 28 | 5.61 Percent Change | Standard Deviation 21.672 |
| CD24Fc 240 mg | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in HDL-C at Week 28 | 0.30 Percent Change | Standard Deviation 0.61 |
| CD24Fc 240 mg | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in Triglycerides at Week 28 | -2.77 Percent Change | Standard Deviation 48.32 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in HDL-C at Week 28 | 3.20 Percent Change | Standard Deviation 19.512 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in Total Cholesterol at Week 6 | 1.53 Percent Change | Standard Deviation 10.947 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in Total Cholesterol at Week 28 | 2.40 Percent Change | Standard Deviation 18.037 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in HDL-C at Week 6 | 0.88 Percent Change | Standard Deviation 6.655 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in Triglycerides at Week 28 | -1.80 Percent Change | Standard Deviation 46.31 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides | Percent Change from Baseline in Triglycerides at Week 6 | -7.30 Percent Change | Standard Deviation 23.607 |
Secondary
Percent Change From Baseline in Troponin I and Troponin T Serum Levels
Troponin I and troponin T blood concentrations were to be measured. The percent change from baseline at Week 28 was to be presented.
Time frame: Baseline and Week 28
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. Results for baseline and/or Week 28 were not quantifiable for any participants, so the change from baseline analysis could not be performed and no participants were analyzed.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Percent Change From Baseline in Troponin I and Troponin T Serum Levels | Percent Change from Baseline in Troponin I | — |
| Unknown | Percent Change From Baseline in Troponin I and Troponin T Serum Levels | Percent Change from Baseline in Troponin T | — |
Secondary
Percent Change From Baseline in Tumor Necrosis Factor (TNF)+ Peripheral Blood Mononuclear Cells (PBMCs)
The percent change from baseline in the percentage of PBMCs that were TNF+ at Weeks 6 and 28 was to be presented.
Time frame: Baseline, Week 6, and Week 28
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. Data for this outcome measure could not be collected because the laboratory was unable to run the assay. Therefore, no participants were analyzed.
Secondary
Percent Change From Baseline in Whole Blood Soluble Cluster of Differentiation 14 (sCD14) Concentration
The percent change from baseline in sCD14 concentration in whole blood at Weeks 6 and 28 was to be presented.
Time frame: Baseline, Week 6, and Week 28
Population: The intended analysis population was all randomized participants who received ≥1 dose of study drug. Data for this outcome measure could not be collected because the laboratory was unable to run the assay. Therefore, no participants were analyzed.
Other Pre-specified
Change From Baseline in Aortic F-fluorodeoxyglucose (FDG) Uptake
Arterial FDG uptake is used to evaluate arterial inflammation. Arterial FDG uptake was to be measured by positron emission tomography-computed tomography (PET/CT) scan at Baseline and Week 24 in the aortic root and the same superior vena cava, then reported as the aortic uptake value divided by the superior vena cava uptake value, the target-to-background ratio (TBR). The change from baseline at Week 24 was to be presented.
Time frame: Baseline and Week 24
Population: The intended analysis population was the first 12 randomized participants who received ≥1 dose of study drug, had LDL levels greater than 125 mg/dL, and volunteered for this optional measurement. No participants volunteered for the PET/CT scans required for this outcome measure. Therefore, no participants were analyzed.