Efprezimod Alfa (CD24Fc, MK-7110) Administration to Decrease Low-Density Lipoprotein (LDL) and Inflammation in Human Immunodeficiency Virus (HIV) Patients (CALIBER) (MK-7110-003)
Condition: HIV Infections; Dyslipidemias
MeSH terms: Dyslipidemias; Inflammation
Intervention: Efprezimod alfa (human CD24 extracellular domain and human IgG1 Fc fusion protein); Saline Solution
Intervention description: Efprezimod alfa will be given as IV infusion, 240 mg per infusion, on Days 0, 14, and 28.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double blinded, placebo controlled.
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 8.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: HIV Dyslipidemias; CD24Fc; HIV Chronic Inflammation; LDL Reduction

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.
    

Eligibility 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 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.