Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

CD24Fc Administration to Decrease LDL and Inflammation in HIV Patients (CALIBER) (CALIBER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03960541
Recruitment Status : Not yet recruiting
First Posted : May 23, 2019
Last Update Posted : May 23, 2019
Sponsor:
Collaborator:
University of Maryland
Information provided by (Responsible Party):
OncoImmune, Inc.

Brief Summary:
This is a phase 2, randomized, single-blinded, placebo-controlled clinical trial. The intervention drug will be CD24Fc (IV infusion). A cohort of 64 patients with HIV on antiretroviral therapy will be randomized in a 1:1 fashion to be administered 7 doses of CD24Fc (240mg IV infusion) or placebo q2w during a 12-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, single-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, 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 cholesterol, leptin, 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 12-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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, single blinded, placebo controlled.
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Single-blinded, Placebo-controlled Clinical Trial on CD24Fc Administration to Decrease LDL and Inflammation in HIV Patients, Both as Markers of Efficacy and Cardiovascular Risk Reduction (CALIBER)
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: CD24Fc Treatment
The intervention drug will be CD24Fc (IV infusion). Patients with HIV on antiretroviral therapy will be administered 7 doses of CD24Fc (240mg IV infusion) q2w during a 12-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 7 doses in 12 week interval.
Other Name: CD24Fc

Placebo Comparator: Placebo
The intervention drug will be CD24Fc (IV infusion). Patients with HIV on antiretroviral therapy will be administered 7 doses of normal saline solution (150 ml, IV infusion) q2w during a 12-week window, followed by a 24-week follow-up window to assess safety and changes in LDL.
Drug: Saline Solution
Normal Saline Solution will be given as placebo with IV infusion, 150 ml per infusion, q2w, total 7 doses in 12 weeks.
Other Name: Saline




Primary Outcome Measures :
  1. To evaluate the change in LDL during 14-week dosing period of CD24Fc. [ Time Frame: 14 weeks ]
    The percentage reduction in LDL level from the baseline (predosing) to 14 weeks (2 weeks after 7 dosings of drug).


Secondary Outcome Measures :
  1. Levels of total cholesterol, HDL, and triglycerides [ Time Frame: 14 weeks. ]
    Percent change in levels of total cholesterol, HDL, and triglycerides from baseline to Weeks 14 between placebo and intervention arms.

  2. Markers of immune activation (CD4 and CD8 T cells, IFN, TNF, sCD14) [ Time Frame: 14 weeks. ]
    Percent change in markers of immune activation (CD4 and CD8 T cells, IFN, TNF, sCD14) from baseline to Week 14 between placebo and intervention arms.

  3. Size of HIV reservoirs [ Time Frame: 14 weeks. ]
    Change in proviral DNA from baseline to Week 14 between placebo and intervention arms.

  4. Myocardial damage (measured by Troponin I) [ Time Frame: 36 weeks. ]
    Percent change from baseline to week 36 in Troponin I between placebo and intervention arms.

  5. Hepatic steatosis, as determined by transient elastography [ Time Frame: 36 weeks. ]
    Change in percent of hepatic steatosis (by CAP measurement) and fibrosis (by KPA) as determined by transient elastography from baseline to week 36 between placebo and intervention arms.

  6. Level of leptin [ Time Frame: 14 weeks. ]
    Percent change in leptin from baseline to Week 14 between placebo and intervention arms.

  7. Hemoglobin A1c [ Time Frame: 14 weeks. ]
    Percent change in hemoglobin A1c from baseline to Week 14 between placebo and intervention arms.

  8. Area under the plasma concentration versus time curve (AUC) of CD24Fc in first 6 patients. [ Time Frame: 36 weeks. ]
    Area under the plasma concentration versus time curve (AUC) determined by plasma concentration of CD24Fc from different time points during entire study period of 36 weeks from the first 6 patients.

  9. The number of patients who develop Anti-drug antibody in 36 weeks of study period [ Time Frame: 36 weeks. ]
    To determine the number of patients who have new anti-CD24Fc antibody in 36 weeks.


Other Outcome Measures:
  1. To evaluate the impact of CD24Fc on arterial inflammation measured by FDG-PET. [ Time Frame: 36 weeks ]
    Change in baseline arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET as a measure of vascular inflammation, between baseline and week 36, for a subset of 12 patients. The 12 patients selected will have an LDL<125 and will not have partook 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.


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

Inclusion Criteria:

  1. Provision of signed and dated informed consent form
  2. Stated willingness to comply with all study procedures and availability for the duration of the study
  3. At least 50 years of age or older at screening
  4. Available for clinical follow-up through Week 36 after enrollment
  5. Chronic HIV infection based on documentation from a primary care physician that the patient has HIV and is on antiretroviral therapy
  6. On a stable regimen of ART. The subject is expected to continue on an accepted ART regimen for the duration of the study (through week 36).

    1. Accepted combinations

      • FTC/TAF [Descovy®], FTC/TDF [Truvada®], or ABC/3TC [Epzicom®] PLUS

      o Ritonavir (r) and darunavir (DRV), or

      o Raltegravir (RAL), or

      o Elvitegravir (EVG) ± Cobicistat (c), or

      o Dolutegravir (DTG), or

      o Rilpivirine (RPV)

    2. Accepted fixed dose combinations

      • FTC/RPV/TAF [Odefsey®]

      • FTC/RPV/TDF [Complera®]

      • EVG/c/TAF/FTC [Genvoya®]

      • EVG/c/TDF/FTC [Stribild®]

      • DTG/ABC/3TC [Triumeq®]

      • DTG/TAF/FTC [Biktarvy®]

    3. Alternative ART regimens will be considered on an individual basis, based on available DDI data at the discretion of the principal investigator
  7. At least 2 years of maintained HIV RNA < 50 copies/mL (or < LLOQ if the local laboratory assay's LLOQ is ≥50 copies/mL) prior to Screening and HIV RNA<50 at screening.
  8. CD4 count>200 cells/mm3 at Screening
  9. Ability to communicate effectively with the study investigator and other key personnel
  10. Subjects must have a primary care doctor for their medical management
  11. Willing to donate blood for sample storage to be used for future research
  12. 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 • At least one form of effective contraception from the list below, 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.: i. Intrauterine device with a failure rate of <1% per year ii. Tubal sterilization iii. Bilateral tubal occlusion iv. Vasectomy in a male v. Female barrier method (diaphragm or cervical cap) vi. Hormonal methods

1. Oral contraceptives 2. Injectable progesterone 3. Implants of levonorgestrel or etonorgestrel 4. Transdermal contraceptive patch 5. Contraceptive vaginal ring

  1. 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.

    13. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration

Exclusion Criteria:

  1. 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 subject treatment, assessment of compliance with the protocol; subjects 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 patient'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 PI may cause ongoing interference with host immunity; subjects under evaluation for malignancy are not eligible.
  2. 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. ALT or AST 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
  3. Poorly controlled diabetes as indicated by a screening glycosylated hemoglobin (HbA1c) >10
  4. 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
  5. Hyperlipidemia (defined as an LDL≥190 mg/dL), that is not being treating with a statin, since statin therapy would be the standard of care for these patients., Patients with hyperlipidemia who are deemed ineligible to be on statin therapy by a treating physician will not be excluded.
  6. 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.

    Female-specific criteria:

  7. Woman 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


Contacts
Layout table for location contacts
Contact: Poonam Mathur, DO, MPH (443) 326-0506 pmathur@ihv.umaryland.edu

Locations
Layout table for location information
United States, Maryland
Institute of Human Virology, University of Maryland Baltimore Not yet recruiting
Baltimore, Maryland, United States, 21201
Contact: Poonam Mathur, DO, MPH         
Sponsors and Collaborators
OncoImmune, Inc.
University of Maryland
Investigators
Layout table for investigator information
Principal Investigator: Shyamasundaran Kottilil, MD Institute of Human Virology, University of Maryland Baltimore

Layout table for additonal information
Responsible Party: OncoImmune, Inc.
ClinicalTrials.gov Identifier: NCT03960541     History of Changes
Other Study ID Numbers: HP-00086029
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
Inflammation
HIV Infections
Dyslipidemias
Pathologic Processes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Lipid Metabolism Disorders
Metabolic Diseases