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

NCT01731691 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: Prolastin-C in HIV disease
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Disease

Outcome Measures

Primary Outcomes (7)

• CD4 Counts

  It has been observed that CD4 counts and cholesterol levels are correlated and that there is cyclic variation in individuals with and without HIV.

  9 weeks after initiation of treatment

• CD8

  It has been observed that CD4 counts and cholesterol levels are correlated and that there is cyclic variation in individuals with and without HIV.

  9 weeks after initiation of treatment

• CD4/CD8 Ratio

  It has been observed that CD4 counts and cholesterol levels are correlated and that there is cyclic variation in individuals with and without HIV.

  9 weeks after initiation of treatment

• Alpha-1 Proteinase Inhibitor

  weekly for 8 weeks

• sj/betaTrec Ratio

  weekly for 8 weeks

• High Density Lipoprotein (HDL)

  weekly for 8 weeks

• Low Density Lipoprotein (LDL)

  weekly for 8 weeks

Study Arms (3)

α1 Proteinase Inhibitor in HIV disease

EXPERIMENTAL

α1Proteinase Inhibitor (120mg/kg Prolastin-C) weekly for 8 weeks

Biological: α1 Proteinase Inhibitor

Placebo in HIV disease

PLACEBO COMPARATOR

Placebos weekly for 8 weeks

Drug: Placebos

Uninfected controls

NO INTERVENTION

Blood collection only for 8 weeks

Interventions

α1 Proteinase Inhibitor BIOLOGICAL

Prolastin-C treatment in HIV disease will be compared with placebo treatment in HIV disease and no treatment in uninfected volunteers.

Also known as: Prolastin, Prolastin-C, Zemaira, Glassia

α1 Proteinase Inhibitor in HIV disease

Placebos DRUG

Placebo treatment in HIV disease will be compared with Prolastin-C treatment in HIV disease and no treatment in uninfected volunteers.

Also known as: Saline

Placebo in HIV disease

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Not have previously received α1PI augmentation therapy
• Age at least 18 years and under 65 years
• Capacity for and commitment to attend all protocol scheduled visits at ACRIA
• Life expectancy of greater than 5 years
• 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
• HIV-1 patients must have active α1PI below 11 uM (normal is 18-53 uM)
• 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

You may not qualify if:

• Recent illness that will prevent the patient from participating in required study activities
• Patients receiving other investigational agents
• Patients with known malignancies
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Prolastin-C
• IgA deficient patients
• Patients with ≥1000 HIV-1 RNA copies/ mL
• Patients with \>600 CD4 cells/uL
• 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
• Pregnant and breastfeeding women
• Refusal to give informed consent

Sponsors & Collaborators

• Institute for Human Genetics and Biochemistry: lead
• AIDS Community Research Initiative of America: collaborator
• Grifols Biologicals, LLC: collaborator

Study Sites (1)

ACRIA

New York, New York, 10018, United States

Location

Related Publications (3)

• Bristow CL, Babayeva MA, LaBrunda M, Mullen MP, Winston R. alpha1Proteinase inhibitor regulates CD4+ lymphocyte levels and is rate limiting in HIV-1 disease. PLoS One. 2012;7(2):e31383. doi: 10.1371/journal.pone.0031383. Epub 2012 Feb 17.

  PMID: 22363634 BACKGROUND

• Bristow CL, Patel H, Arnold RR. Self antigen prognostic for human immunodeficiency virus disease progression. Clin Diagn Lab Immunol. 2001 Sep;8(5):937-42. doi: 10.1128/CDLI.8.5.937-942.2001.

  PMID: 11527807 BACKGROUND

• Bristow CL, Ferrando-Martinez S, Ruiz-Mateos E, Leal M, Winston R. Development of Immature CD4+CD8+T Cells Into Mature CD4+ T Cells Requires Alpha-1 Antitrypsin as Observed by Treatment in HIV-1 Infected and Uninfected Controls. Front Cell Dev Biol. 2019 Nov 21;7:278. doi: 10.3389/fcell.2019.00278. eCollection 2019.

  PMID: 31824943 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

alpha 1-Antitrypsin; Sodium Chloride

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed; Technical problems with measurement leading to unreliable or uninterpretable data.

Results Point of Contact

• Title: Dr. Cynthia L. Bristow
• Organization: Institute for Human Genetics and Biochemistry

cynthia.bristow@stonybrook.edu

631-444-6238

Study Officials

• Cynthia Bristow, PhD

  Institute for Human Genetics and Biochemistry

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Study Start: April 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: August 31, 2020
• Results First Posted: August 31, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)