Safety and Efficacy of (α1Proteinase Inhibitor, α1PI) in HIV Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Institute for Human Genetics and Biochemistry
Sponsor:
Collaborators:
AIDS Community Research Initiative of America
Grifols Biologicals Inc.
Information provided by (Responsible Party):
Institute for Human Genetics and Biochemistry
ClinicalTrials.gov Identifier:
NCT01731691
First received: November 19, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

Our primary objective is to further characterize the mechanism by which alpha-1PI regulates CD4 counts.

HIV-1 infected patients will be initiated on PROLASTIN®-C (Alpha-1 Proteinase Inhibitor [Human], Grifols Biotherapeutics Inc.) or placebo. Uninfected volunteers will be untreated and will be monitored for comparison.


Condition Intervention Phase
HIV Disease
Biological: α1 Proteinase Inhibitor
Biological: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Double Blind, Randomized Trial to Evaluate the Safety and Efficacy of 8 Weekly Doses of Prolastin®-C (α1Proteinase Inhibitor, α1PI) in Human Immunodeficiency Virus-Infected Subjects Who Are 18 to 65 Years of Age and on Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by Institute for Human Genetics and Biochemistry:

Primary Outcome Measures:
  • CD4 counts [ Time Frame: 9 weeks after initiation of treatment ] [ Designated as safety issue: No ]
    It has been observed that CD4 counts and cholesterol levels are correlated and that there is cyclic variation in individuals with and without HIV.


Secondary Outcome Measures:
  • cholesterol levels [ Time Frame: 9 weeks after initiation of treatment ] [ Designated as safety issue: No ]
    CD4 T cells transport lipoproteins through blood and lymph and are correlated with cholesterol levels. Regulation of CD4 counts includes regulation of cholesterol levels.


Estimated Enrollment: 20
Study Start Date: April 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: α1 Proteinase Inhibitor in HIV disease
α1Proteinase Inhibitor (120mg/kg Prolastin-C) weekly for 8 weeks
Biological: α1 Proteinase Inhibitor
Prolastin-C treatment in HIV disease will be compared with placebo treatment in HIV disease and no treatment in uninfected volunteers.
Other Names:
  • Prolastin
  • Prolastin-C
  • Zemaira
  • Glassia
Placebo Comparator: Placebo in HIV disease
Placebo (saline) weekly for 8 weeks
Biological: Placebo
No Intervention: Uninfected controls
Blood collection only for 8 weeks

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. HIV-1 patients must have confirmed HIV-1 disease, diagnosed using the standard criteria and be on antiretroviral therapy. Uninfected volunteers will be age and gender matched.
  2. HIV-1 patients must have measurable disease, defined as HIV-1 infected patients on antiretroviral therapy with undetectable HIV RNA (<1000 HIV RNA copies/ml) and CD4 counts more than 200 and less than 600 cells/uL.
  3. Not have previously received α1PI augmentation therapy
  4. Age at least 18 years and under 65 years
  5. Capacity for and commitment to attend all protocol scheduled visits at ACRIA
  6. Life expectancy of greater than 5 years
  7. Patients must have lab values within the limits defined below:

    • WBC >4,1000/uL
    • ANC >1,000/uL
    • platelets >100,000//uL
    • total bilirubin 2-12 mg/dL
    • AST(SGOT)/ALT(SGPT) < or = 2.5 X upper limit of normal
    • creatinine Male : 0.50-1.30 mg/dL Female: 0.40-1.20 mg/dL
  8. HIV-1 patients must have active α1PI below 11 uM (normal is 18-53 uM)
  9. HIV-1 patients must have one year history (prior to the study) with CD4+ lymphocytes at levels greater than 200 and less than 400 cells/uL
  10. HIV-1 patients must have absence of symptoms suggestive of HIV-1 disease progression
  11. HIV-1 patients must have adequate suppression of virus (<400 HIV RNA/mL)
  12. HIV-1 patients must have a history of compliance with antiretroviral medication based on undetectable virus levels
  13. No evidence of malignancy
  14. The effects of Prolastin-C on the developing human fetus at the recommended therapeutic dose are unknown: At any time throughout the study, from the signing of the informed consent form until after the last study visit, all female and male subjects who are biologically capable of having children must agree and commit to use a reliable method of birth control.
  15. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  1. Recent illness that will prevent the patient from participating in required study activities
  2. Patients receiving other investigational agents
  3. Patients with known malignancies
  4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Prolastin-C
  5. IgA deficient patients
  6. Patients with ≥1000 HIV-1 RNA copies/ mL
  7. Patients with >600 CD4 cells/uL
  8. Uncontrolled illness including, but not limited to, ongoing or active infection, myeloid dysplastic syndrome, anemia, bone marrow failure, DiGeorge Syndrome, thymic disorders, or psychiatric illness/social situations that would limit compliance with study requirements
  9. Pregnant and breastfeeding women
  10. Refusal to give informed consent
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01731691

Contacts
Contact: Cynthia Bristow, PhD 631 444 6238 cynthia.bristow@stonybrook.edu
Contact: Jerry Ernst, MD 212 924 3934 JErnst@amidacareny.org

Locations
United States, New York
ACRIA Recruiting
New York, New York, United States, 10018
Contact: Yuriy Akulov, MD, PhD    212-924-3934 ext 124    yakulov@acria.org   
Contact: Jerry Ernst, MD    (212) 924-3934    JErnst@amidacareny.org   
Sub-Investigator: Jerry Ernst, MD         
Principal Investigator: Cynthia L Bristow, PhD         
Sponsors and Collaborators
Institute for Human Genetics and Biochemistry
AIDS Community Research Initiative of America
Grifols Biologicals Inc.
Investigators
Principal Investigator: Cynthia Bristow, PhD Institute for Human Genetics and Biochemistry
  More Information

Additional Information:
Publications:
Responsible Party: Institute for Human Genetics and Biochemistry
ClinicalTrials.gov Identifier: NCT01731691     History of Changes
Other Study ID Numbers: Prolastin-C in HIV disease
Study First Received: November 19, 2012
Last Updated: June 23, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Alpha 1-Antitrypsin
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serine Proteinase Inhibitors
Trypsin Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014