Therapy to Elevate CD4 Counts in HIV-1 Disease

NCT01370018 | Completed Phase 2 Results FDA Drug

• 1 other identifier: R06-005
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

For more than 20 years, alpha-1-proteinase inhibitor therapy has been the standard treatment for patients who have inherited alpha-1-proteinase inhibitor deficiency. Adult patients with this condition eventually develop emphysema. Most HIV-1 patients who have low viral load also have alpha-1-proteinase inhibitor deficiency. The number of CD4 cells in blood increases when alpha-1-proteinase inhibitor increases. Patients will be asked to participate in a pilot study to see whether the use of Zemaira® (alpha-1-proteinase inhibitor) can increase blood levels of alpha-1-proteinase inhibitor and consequently increase CD4 counts.

Conditions

HIV Disease

Keywords

CD4 counts; cholesterol

Outcome Measures

Primary Outcomes (1)

• CD4/CD8 Ratio

  9 weeks after initiation of treatment

Study Arms (1)

alpha-1 proteinase inhibitor in HIV

EXPERIMENTAL

HIV-1 infected individuals treated with Alpha-1 proteinase inhibitor

Biological: alpha-1-Proteinase Inhibitor

Interventions

alpha-1-Proteinase Inhibitor BIOLOGICAL

Alpha-1-Proteinase Inhibitor was delivered I.V. A patient weighing 150 pounds was infused with approximately ½ cup containing 8.4 grams of alpha-1-Proteinase Inhibitor. Patients were admitted to hospital for infusion. The I.V. infusion was approximately 1 teaspoon/minute. Patients received weekly infusions of alpha-1-Proteinase Inhibitor for 8-12 weeks. At the time of infusion, 40ml (3 Tablespoons) of blood was collected (IRB approval #R04-003). The blood sample was used to monitor viral load, CD4 cell numbers, and alpha-1-Proteinase Inhibitor.

Also known as: Zemaira, Prolastin

alpha-1 proteinase inhibitor in HIV

Eligibility Criteria

• Age: 30 Years - 70 Years
• Gender Eligibility Details: Female subjects were not included in this pilot study to avoid pregnancy-related issues.
• 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. Patients with inherited alpha-1 proteinase inhibitor deficiency (PIzz) must not have previously received alpha-1 proteinase inhibitor 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 (\<500 HIV-1 RNA copies/ml) and CD4 counts more than 200 and less than 400 cells/uL.
• Age at least 18 years and under 65 years.
• HIV-1 patients must have active alpha-1 proteinase inhibitor below 11uM (normal is 18-53 uM).
• HIV-1 patients must have one year history (prior to the study) with CD4 counts greater than 200 and less than 400 cells/uL.
• Volunteers must have no evidence of malignancy.

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.
• Patients with more than 500 HIV RNA copies/mL.
• Patients with more than 400 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.

Sponsors & Collaborators

• Institute for Human Genetics and Biochemistry: lead
• CSL Behring: collaborator

Study Sites (1)

Cabrini Medical Center

New York, New York, 10003, United States

Location

Related Publications (3)

• Bristow, C.L., Cortes, J., Mukhtarzad R., Trucy, M., Franklin, A., Romberg, V., Winston, R. 2010. α1Antitrypsin therapy increases CD4+ lymphocytes to normal values in HIV-1 patients. In Soluble Factors Mediating Innate Immune Responses to HIV Infection, (ed. M. Alfano). Bentham Science Publishers, http://www.alpha1biologics.com/BristowChapter.pdf

  RESULT

• Bristow CL, Modarresi R, Babayeva MA, LaBrunda M, Mukhtarzad R, Trucy M, Franklin A, Reeves RE, Long A, Mullen MP, Cortes J, Winston R. A feedback regulatory pathway between LDL and alpha-1 proteinase inhibitor in chronic inflammation and infection. Discov Med. 2013 Nov;16(89):201-18.

  PMID: 24229737 RESULT

• 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

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

Limitations and Caveats

One HIV infected patient enrolled, but entered the study with elevated inflammatory markers which were were not within the eligibility criteria.

Results Point of Contact

• Title: Cynthia L. Bristow, MS, PhD
• Organization: Institute for Human Genetics and Biochemistry

cynthia.bristow@alpha1biologics.com

6314446238

Study Officials

• Cynthia L Bristow, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Jose Cortes, MD

  Beth Israel Medical Center

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Mount Sinai School of Medicine

Study Record Dates

• First Submitted: June 6, 2011
• First Posted: June 9, 2011
• Study Start: December 1, 2006
• Primary Completion: February 1, 2007
• Study Completion: February 1, 2007
• Last Updated: September 28, 2021
• Results First Posted: September 28, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)