Safety and Efficacy Study of AGS-004 During Analytical Treatment Interruption

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Argos Therapeutics
ClinicalTrials.gov Identifier:
NCT01069809
First received: February 16, 2010
Last updated: September 23, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to determine the safety and effectiveness of AGS-004, an immune therapy, for HIV-infected individuals. Safety and effectiveness will be tested while the individuals are both taking antiretroviral therapy (ART) medication and interrupting ART medication.


Condition Intervention Phase
HIV Infection
Biological: AGS-004
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Phase 2B Study Testing the Efficacy and Safety of AGS-004 on Host Control of HIV Replication During Analytical Treatment Interruption

Resource links provided by NLM:


Further study details as provided by Argos Therapeutics:

Primary Outcome Measures:
  • Compare the anti-HIV effects of AGS-004 versus Placebo as measured by new HIV Viral Load setpoint after a 12 week Analytical Treatment Interruption [ Time Frame: 38 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate AGS-004 versus Placebo for change in plasma HIV Viral Load levels from the value just before initiation of ART to the value at the end of the 12 week ATI. [ Time Frame: 38 weeks ] [ Designated as safety issue: No ]
  • Evaluate AGS-004 versus Placebo for change from Baseline in CD4 T-Cell absolute and percentage values at Week 26 and at the end of Step 4 (for subjects continuing ATI) [ Time Frame: 38 weeks (62 weeks for subjects continuing ATI in Step 4) ] [ Designated as safety issue: Yes ]
  • Evaluate AGS-004 versus Placebo for effects on HIV viral kinetics during the 12 week ATI, as measured my mean or median levels of plasma HIV Viral Load; assessed throughout and at the end of Step 4 (for subjects continuing ATI) [ Time Frame: 38 weeks (62 weeks for subjects continuing ATI in Step 4) ] [ Designated as safety issue: No ]
  • Evaluate AGS-004 versus Placebo for change from Baseline in TEAEs, clinical laboratory evaluations, and clinical assessments. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Evaluate AGS-004 versus Placebo for change in inflammatory markers over treatment period and ATI [ Time Frame: 38 Weeks (62 weeks for subjects continuing ATI in Step 4) ] [ Designated as safety issue: Yes ]
  • Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline in T-cell response. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline of the extent of viral evolution. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline in the chromosomally integrated viral reservoir. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: July 2010
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AGS-004
HIV-1 Immune Therapy
Biological: AGS-004
HIV-1 Immune Therapy
Placebo Comparator: Inactive Injection
Inactive Placebo Injection
Biological: Placebo
Inactive Placebo Injection

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females ≥ 18 to 60 years of age.
  2. HIV infection.
  3. Stable ART regimen for ≥ 3 months prior to Screening.
  4. HIV VL level ≤ 400 copies/mL for ≥ 2 months prior to Screening.
  5. HIV VL level ≤ 50 copies/mL at Screening.
  6. CD4+ T cell count ≥ 450 cells/mm3 at Screening.
  7. Pre-ART nadir CD4+ T cell counts ≥ 200 cells/mm³.
  8. Availability of an adequate sample of frozen plasma most recently collected (no more than 90 days and preferably within 30 days) before starting ART.
  9. Laboratory values within pre-defined limits at Screening and Eligibility.
  10. Negative serum pregnancy test at Screening and Eligibility for females with reproductive potential, and agreement of all subjects to use a reliable form of contraception during the study and for 12 weeks after the last dose of study drug.
  11. Able and willing to give adequate written informed consent, to communicate effectively with study personnel, and willing to be compliant with protocol requirements.

Exclusion Criteria:

  1. HIV-2 antibody positive at Screening Visit.
  2. Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody (if positive HCV antibody, HCV RNA must be negative).
  3. Untreated syphilis infection (positive rapid plasma reagin [RPR]).
  4. Changes in ART regimen due to virologic breakthrough.
  5. History of lymph node irradiation or dissection.
  6. Prior use of any HIV immunotherapy or vaccine within 9 months prior to Screening.
  7. Prior participation in an AGS-004 clinical study.
  8. Treatment interruption of ART for > 1 month since starting the ART from which the pre-ART plasma sample was drawn.
  9. Any acute infection or medical illness within 14 days prior to Screening and throughout the pre-treatment evaluation phase (Step 1).
  10. Initiation of ART during the acute HIV infection stage, if date of infection known (acute infection defined as < 6 months between date of HIV infection and ART start date).
  11. Pregnancy or breast-feeding.
  12. Receipt of any immune modulators or suppressors within 30 days prior to Screening and throughout the pre-treatment evaluation phase (Step 1).
  13. Evidence of hepatic decompensation in cirrhotic subjects: history of ascites, hepatic encephalopathy, or bleeding esophageal varices, or screening laboratory results of any of the following:

    • International Normalized Ratio (INR) of ≥ 1.5 X upper limit of normal (ULN);
    • Serum albumin < 3.3 g/dL;
    • Serum total bilirubin > 1.8 X ULN, unless history of Gilbert's disease or deemed related to treatment with atazanavir.
  14. History or other clinical evidence of significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction, significant arrhythmia) or clinically significant electrocardiogram (ECG) abnormalities.
  15. History of moderate or severe renal impairment (i.e., persistent history of creatinine clearance < 50 mL/min) or any other renal disorder deemed clinically significant by the investigator.
  16. Prior history of an acquired immunodeficiency syndrome (AIDS) defining condition.
  17. History or other evidence of severe illness, malignancy, immunodeficiency other than HIV, or any other condition that would make the subject unsuitable for the study in the opinion of the investigator.
  18. Known allergy or sensitivity to the components of the investigational immunotherapy.
  19. Active drug or alcohol use or dependence that would interfere with adherence to study requirements in the opinion of the investigator.
  20. Use of systemic corticosteroids and use of topical steroids over a total area exceeding 15 cm² within 30 days prior to Screening.
  21. Any investigational antiretroviral agents or use of a CCR5 inhibitor at Screening.
  22. Active autoimmune disease or condition.
  23. Participation in another investigational clinical study within the previous 30 days or use of investigational agents.
  24. Body weight less than 30 kg.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01069809

Locations
United States, California
UCDavis Research Office at CARES
Sacramento, California, United States, 95811
United States, New York
Jacobi & North Central Bronx Hospitals
Bronx, New York, United States, 10461
United States, North Carolina
AIDS Clinical Trials Unit
Chapel Hill, North Carolina, United States, 27514
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Division of Infectious Disease and HIV Medicine Partnership Comprehensive Care Practice
Philadelphia, Pennsylvania, United States, 191002
Canada, Ontario
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 816
Canada, Quebec
Clinique médicale l'Actuel
Montréal, Quebec, Canada, H2L4P9
Clinique Médical du Quartier Latin
Montréal, Quebec, Canada, H2L5B1
Montreal Chest Institute, Immunodeficiency Dept.
Montréal, Quebec, Canada, H2X 2P4
Sponsors and Collaborators
Argos Therapeutics
Investigators
Principal Investigator: Jeffery Jacobson, MD Drexel University
  More Information

Additional Information:
No publications provided

Responsible Party: Argos Therapeutics
ClinicalTrials.gov Identifier: NCT01069809     History of Changes
Obsolete Identifiers: NCT00595192
Other Study ID Numbers: AGS-004-003, HHSN266200600019C, ES-11702
Study First Received: February 16, 2010
Last Updated: September 23, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on April 16, 2014