AzTrials
AzTrials

HIV InfectionsPhase 2CALIBERNCT03960541

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

A Phase 2 study testing Efprezimod alfa (human CD24 extracellular domain and human IgG1 Fc fusion protein) and Saline Solution in people with HIV Infections and Dyslipidemias, run by Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
HIV Infections, Dyslipidemias
What is being tested?
Efprezimod alfa (human CD24 extracellular domain and human IgG1 Fc fusion protein) and Saline Solution
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
8 participants
Where
1 siteUnited States
Study dates
31 Aug 2020to 27 May 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 18Show fewer
  • 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

Who cannot join

  • Has a current or prior history of any of the following:
  • 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
  • Poor venous access interfering with required study blood collection
  • Solid organ transplantation
  • Significant pulmonary disease, significant cardiac disease, or porphyria
  • Uncontrolled chronic hepatitis B infection (surface antigen positive with detectable HBV DNA as noted in participant's medical documentation from a treating physician)
Show all 26Show fewer
  • Chronic, current/active hepatitis C infection
  • Unstable psychiatric disease. (Subjects with psychiatric illness that is well-controlled on a stable treatment regimen or currently not requiring medication may be included.)
  • 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:
  • Neutrophil count <750 cells/mm^3
  • Hemoglobin level <10 g/dL
  • Platelet count ≤50,000 cells/mm^3
  • Estimated glomerular filtration rate, calculated by the chronic kidney disease epidemiology collaboration formula: <30 mL/min/1.73 m^2
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥5 times upper limit of normal (ULN)
  • Total bilirubin level ≥2.0 times ULN, except in subjects with Gilbert's syndrome or other clinical explanation at the discretion of the PI
  • 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:
  • Hematologic stimulating agents, erythropoiesis stimulating agents (ESAs), granulocyte colony stimulating factor (GCSF), thrombopoeitin (TPO) mimetics
  • 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)
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Institute of Human Virology, University of Maryland Baltimore

    Baltimore, Maryland, 21201

Other trials in United States

About this study

Official title: CD24Fc Administration to Decrease LDL and Inflammation in HIV Patients, Both as Markers of Efficacy and Cardiovascular Risk Reduction (CALIBER)

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.

Read the 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.

Being tested
Efprezimod alfa (human CD24 extracellular domain and human IgG1 Fc fusion protein), Saline Solution
Keywords
HIV Dyslipidemias, CD24Fc, HIV Chronic Inflammation, LDL Reduction
Medical subject headings
HIV Infections, Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Efprezimod alfa (human CD24 extracellular domain and human IgG1 Fc fusion protein)Drug

    Also called CD24Fc, MK-7110

    Efprezimod alfa will be given as IV infusion, 240 mg per infusion, on Days 0, 14, and 28.

  • Saline SolutionDrug

    Also called Saline

    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.

Study groups in NCT03960541
Study groupRoleWhat they receive
Efprezimod alfa TreatmentExperimentalParticipants received an intravenous infusion of 240 mg of efprezimod alfa on Days 0, 14, and 28.
Receives: Drug: Efprezimod alfa (human CD24 extracellular domain and human IgG1 Fc fusion protein)
PlaceboPlacebo comparatorParticipants received an intravenous infusion of placebo (sterile saline solution) on Days 0, 14, and 28.
Receives: Drug: Saline Solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and Week 6

  2. 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.

    Measured: Up to approximately 28 weeks

  3. 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.

    Measured: Up to approximately 4 weeks

Secondary outcomes (17)

  1. 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.

    Measured: Baseline, Week 6, and Week 28

  2. 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.

    Measured: Baseline, Week 6, and Week 28

  3. 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.

    Measured: Baseline, Week 6, and Week 28

  4. 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.

    Measured: Baseline, Week 6, and Week 28

  5. 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.

    Measured: Baseline, Week 6, and Week 28

  6. 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.

    Measured: Baseline, Week 6, and Week 28

  7. 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.

    Measured: Baseline and Week 28

  8. 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.

    Measured: Baseline and Week 28

  9. 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.

    Measured: Baseline and Week 28

  10. 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.

    Measured: Baseline, Week 6, and Week 28

  11. 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.

    Measured: Baseline, Week 6, and Week 28

  12. 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.

    Measured: Predose and 2 hours postdose at the Week 0, 2, and 4 visits; Any time during the Week 6, 16, and 28 visits.

  13. 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.

    Measured: Baseline, Week 6, and Week 28

  14. 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.

    Measured: Baseline and Week 28

  15. 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.

    Measured: Baseline and Week 28

  16. 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.

    Measured: Baseline and Week 28

  17. 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.

    Measured: Baseline and Week 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2019
  2. Study start31 Aug 2020
  3. Primary completion27 May 2021
  4. Study completion27 May 2021

Why it stopped: Business Reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, double blinded, placebo controlled.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03960541
Sponsor's protocol ID
7110-003
Other IDs
CD24Fc-003, HP-00086029, MK-7110-003
Acronym
CALIBER
Status last verified
Jan 2023
First submitted
15 May 2019
Last updated
8 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Tian RR, Zhang MX, Zhang LT, Zhang P, Ma JP, Liu M, Devenport M, Zheng P, Zhang XL, Lian XD, Ye M, Zheng HY, Pang W, Zhang GH, Zhang LG, Liu Y, Zheng YT. CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS. Antiviral Res. 2018 Sep;157:9-17. doi: 10.1016/j.antiviral.2018.07.004. Epub 2018 Jul 3.

    PubMed 29983395

  • Tian RR, Zhang MX, Liu M, Fang X, Li D, Zhang L, Zheng P, Zheng YT, Liu Y. CD24Fc protects against viral pneumonia in simian immunodeficiency virus-infected Chinese rhesus monkeys. Cell Mol Immunol. 2020 Aug;17(8):887-888. doi: 10.1038/s41423-020-0452-5. Epub 2020 May 7. No abstract available.

    PubMed 32382131

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Efprezimod alfa (human CD24 extracellular domain and human IgG1 Fc fusion protein) and Saline Solution in people with HIV Infections and Dyslipidemias, run by Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (time frame: Baseline and Week 6). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03960541, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in