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CD24Fc Administration to Decrease Low-Density Lipoprotein (LDL) and Inflammation in Human Immunodeficiency Virus (HIV) Patients (CALIBER) (MK-7110-003) (CALIBER)

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ClinicalTrials.gov Identifier: NCT03960541
Recruitment Status : Terminated (Business Reasons)
First Posted : May 23, 2019
Last Update Posted : July 15, 2021
Sponsor:
Collaborator:
University of Maryland, Baltimore
Information provided by (Responsible Party):
OncoImmune, Inc.

Brief Summary:
This is a phase 2, randomized, double-blinded, placebo-controlled clinical trial. The intervention drug will be CD24Fc (intravenous [IV] infusion). A cohort of 64 patients with HIV on antiretroviral therapy will be randomized in a 1:1 fashion to be administered 3 doses of CD24Fc (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.

Condition or disease Intervention/treatment Phase
HIV Infections Dyslipidemias Drug: CD24Fc (human CD24 extracellular domain and human IgG1 Fc fusion protein) Drug: Saline Solution Phase 2

Detailed Description:

This study is a phase 2, randomized, placebo-control, double-blinded clinical trial to assess the effect of CD24Fc on reduction in low-density lipoprotein (LDL) among patients with HIV. The effect of CD24Fc 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 CD24Fc will result in significant decreases in LDL in HIV patients. In addition, CD24Fc may reduce leptin and cholesterol, HbA1c, hepatic steatosis and fibrosis, and markers of inflammation in patients with chronic HIV who are virally suppressed on antiretroviral therapy (ART).

In this phase 2 study, a cohort of 64 HIV patients virally suppressed on antiretroviral therapy will be randomized in a 1:1 fashion to receive an intravenous infusion of 240 mg of CD24Fc 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double blinded, placebo controlled.
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: CD24Fc Administration to Decrease LDL and Inflammation in HIV Patients, Both as Markers of Efficacy and Cardiovascular Risk Reduction (CALIBER)
Actual Study Start Date : August 31, 2020
Actual Primary Completion Date : May 27, 2021
Actual Study Completion Date : May 27, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: CD24Fc Treatment
Participants with HIV on antiretroviral therapy will be administered 3 doses of CD24Fc (240mg IV infusion) q2w during a 4-week window, followed by a 24-week follow-up window to assess safety and changes in LDL.
Drug: CD24Fc (human CD24 extracellular domain and human IgG1 Fc fusion protein)
CD24Fc will be given as IV infusion, 240 mg per infusion, q2w, total 3 doses in 4 week interval.
Other Name: CD24Fc

Placebo Comparator: Placebo
Patients with HIV on antiretroviral therapy will be administered 3 doses of normal saline solution (150 ml, IV infusion) q2w during a 4-week window, followed by a 24-week follow-up window to assess safety and changes in LDL.
Drug: Saline Solution
Sterile saline solution (0.9% sodium chloride) will be given as placebo with IV infusion, 150 ml per infusion, q2w, total 3 doses in 4 weeks.
Other Name: Saline




Primary Outcome Measures :
  1. Change from baseline in LDL [ Time Frame: Baseline and Week 6 ]
    The percentage reduction in LDL level from baseline to Week 6 will be reported.

  2. Number of participants with ≥1 adverse event (AE) [ Time Frame: Up to 28 weeks ]
    An AE is any untoward medical occurrence associated with the use of an intervention in participants, whether or not considered intervention-related.

  3. Number of participants withdrawing from study treatment due to AEAE) [ Time Frame: Up to 4 weeks ]
    An AE is any untoward medical occurrence associated with the use of an intervention in participants, whether or not considered intervention-related.


Secondary Outcome Measures :
  1. Change from baseline in total cholesterol, HDL, and triglycerides [ Time Frame: Baseline and Week 6 ]
    The percent change from baseline in levels of total cholesterol, HDL, and triglycerides will be reported.

  2. Change from baseline in total cholesterol, HDL, and triglycerides [ Time Frame: Baseline and Week 28 ]
    The percent change from baseline in levels of total cholesterol, HDL, and triglycerides will be reported.

  3. Change from baseline in markers of immune activation [ Time Frame: Baseline and Week 6 ]
    The percent change in markers of immune activation (CD4 and CD8 T cells, IFN, TNF, sCD14) from baseline to Week 6 will be reported. Cytokine levels will be determined with the Luminex platform.

  4. Change from baseline in markers of immune activation [ Time Frame: Baseline and Week 28 ]
    The percent change in markers of immune activation (CD4 and CD8 T cells, IFN, TNF, sCD14) from baseline to Week 28 will be reported. Cytokine levels will be determined with the Luminex platform.

  5. Change from baseline in size of HIV reservoirs [ Time Frame: Baseline and Week 6 ]
    The change in proviral deoxyribonucleic acid (DNA) from baseline to Week 6 will be reported. Proviral DNA will be quantified by droplet digital polymerase chain reaction (PCR).

  6. Change from baseline in size of HIV reservoirs [ Time Frame: Baseline and Week 28 ]
    The change in proviral DNA from baseline to Week 28 will be reported. Proviral DNA will be quantified by droplet digital PCR.

  7. Myocardial damage (measured by Troponin I) [ Time Frame: Baseline and Week 28 ]
    Percent change from baseline to Week 28 in Troponin I between placebo and intervention arms.

  8. Myocardial damage (measured by Troponin T) [ Time Frame: Baseline and Week 28 ]
    Percent change from baseline to Week 28 in Troponin T between placebo and intervention arms.

  9. Hepatic steatosis and fibrosis, as determined by transient elastography [ Time Frame: Baseline and Week 28 ]
    Change in percent of hepatic steatosis (by CAP measurement) and fibrosis (by KPA) as determined by transient elastography from baseline to week 28 between placebo and intervention arms.

  10. Change from baseline in leptin level [ Time Frame: Baseline and Week 6 ]
    Percent change in leptin from baseline to Week 6 between placebo and intervention arms.

  11. Change from baseline in leptin level [ Time Frame: Baseline and Week 28 ]
    Percent change in leptin from baseline to Week 28 between placebo and intervention arms.

  12. Change from baseline to Week 6 in hemoglobin A1c (HbA1c) [ Time Frame: Baseline and Week 6 ]
    The percent change from baseline to Week 6 in HbA1c will be reported.

  13. Change from baseline to Week 28 in hemoglobin A1c (HbA1c) [ Time Frame: Baseline and Week 28 ]
    The percent change from baseline to Week 28 in HbA1c will be reported.

  14. Area under the plasma concentration versus time curve (AUC) of CD24Fc [ Time Frame: Day 0, Week 2, Week 4, Week 6, Week 16, and Week 28 ]
    The AUC of CD24Fc will be determined from different time points during entire study period of 28 weeks from the first 6 patients.

  15. Number of participants with new anti-drug antibodies [ Time Frame: Up to 28 weeks ]
    The number of participants who have new anti-CD24Fc antibody at Week 28 will be reported.

  16. Change from before to after treatment in interluekin-6 (IL-6) [ Time Frame: Baseline and Week 6 ]
    The change from before treatment (baseline) to after treatment (Week 6) in IL-6 will be reported.

  17. Change from before to after treatment in apolipoprotein B (apoB) [ Time Frame: Baseline and Week 6 ]
    The change from before treatment (baseline) to after treatment (Week 6) in apoB will be reported.

  18. Change from before to after treatment in lipoprotein(a) (Lp[a]) [ Time Frame: Baseline and Week 6 ]
    The change from before treatment (baseline) to after treatment (Week 6) in Lp(a) will be reported.

  19. Change from before to after treatment in urine albumin to creatinine ratio [ Time Frame: Baseline and Week 6 ]
    The change from before treatment (baseline) to after treatment (Week 6) in urine albumin to creatinine ratio will be reported.


Other Outcome Measures:
  1. Effect of CD24Fc on arterial inflammation [ Time Frame: Baseline and Week 28 ]
    Change from baseline to Week 28 in arterial inflammation will be reported. Uptake of fluorodeoxyglucose (FDG) will be assessed by positron emission tomography (PET) in a subset of 12 participants. The 12 participants selected will have an LDL<125 and will not have participated in the PK portion of the study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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 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/mm3
    2. Hemoglobin level <10 g/dL
    3. Platelet count ≤50,000 cells/mm3
    4. Estimated glomerular filtration rate, calculated by the chronic kidney disease epidemiology collaboration formula: <30 mL/min/1.73 m2
    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 treating with 2018 ACC/AHA Cholesterol Clinical Practice guidelines (statins, Ezetimibe, PCSK0 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03960541


Locations
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United States, Maryland
Institute of Human Virology, University of Maryland Baltimore
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
OncoImmune, Inc.
University of Maryland, Baltimore
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
Publications:
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Responsible Party: OncoImmune, Inc.
ClinicalTrials.gov Identifier: NCT03960541    
Other Study ID Numbers: 7110-003
CD24Fc-003 ( Other Identifier: OncoImmune, Inc. )
HP-00086029 ( Other Identifier: OncoImmune, Inc. )
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: July 15, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by OncoImmune, Inc.:
HIV Dyslipidemias
CD24Fc
HIV Chronic Inflammation
LDL Reduction
Additional relevant MeSH terms:
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Dyslipidemias
Inflammation
Pathologic Processes
Lipid Metabolism Disorders
Metabolic Diseases