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

NCT03960541 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: 7110-003CD24Fc-003HP-00086029MK-7110-003
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections; Dyslipidemias

Keywords

HIV Dyslipidemias; CD24Fc; HIV Chronic Inflammation; LDL Reduction

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline and Week 6

• 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.

  Up to approximately 28 weeks

• 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.

  Up to approximately 4 weeks

Secondary Outcomes (17)

• Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein-Cholesterol (HDL-C), and Triglycerides

  Baseline, Week 6, and Week 28

• 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

• Percent Change From Baseline in Interferon (IFN)+ Peripheral Blood Mononuclear Cells (PBMCs)

  Baseline, Week 6, and Week 28

• Percent Change From Baseline in Tumor Necrosis Factor (TNF)+ Peripheral Blood Mononuclear Cells (PBMCs)

  Baseline, Week 6, and Week 28

• Percent Change From Baseline in Whole Blood Soluble Cluster of Differentiation 14 (sCD14) Concentration

  Baseline, Week 6, and Week 28

Other Outcomes (1)

• Change From Baseline in Aortic F-fluorodeoxyglucose (FDG) Uptake

  Baseline and Week 24

Study Arms (2)

Efprezimod alfa Treatment

EXPERIMENTAL

Participants received an intravenous infusion of 240 mg of efprezimod alfa on Days 0, 14, and 28.

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

Placebo

PLACEBO COMPARATOR

Participants received an intravenous infusion of placebo (sterile saline solution) on Days 0, 14, and 28.

Drug: Saline Solution

Interventions

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

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

Also known as: CD24Fc, MK-7110

Efprezimod alfa Treatment

Saline Solution DRUG

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.

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead
• University of Maryland, Baltimore: collaborator

Study Sites (1)

Institute of Human Virology, University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location

Related Publications (2)

• 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.

  PMID: 29983395 BACKGROUND

• 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.

  PMID: 32382131 BACKGROUND

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

HIV Infections; Dyslipidemias

Interventions

Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double blinded, placebo controlled.

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 23, 2019
• Study Start: August 31, 2020
• Primary Completion: May 27, 2021
• Study Completion: May 27, 2021
• Last Updated: February 8, 2023
• Results First Posted: June 8, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)