search
Back to results

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

Primary Purpose

HIV Infection

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AGS-004
Placebo
Sponsored by
Argos Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infection

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCDavis Research Office at CARES
  • Jacobi & North Central Bronx Hospitals
  • AIDS Clinical Trials Unit
  • Duke University Medical Center
  • Division of Infectious Disease and HIV Medicine Partnership Comprehensive Care Practice
  • The Ottawa Hospital
  • Clinique médicale l'Actuel
  • Clinique Médical du Quartier Latin
  • Montreal Chest Institute, Immunodeficiency Dept.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AGS-004

Inactive Injection

Arm Description

HIV-1 Immune Therapy

Inactive Placebo Injection

Outcomes

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

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.
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)
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)
Evaluate AGS-004 versus Placebo for change from Baseline in TEAEs, clinical laboratory evaluations, and clinical assessments.
Evaluate AGS-004 versus Placebo for change in inflammatory markers over treatment period and ATI
Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline in T-cell response.
Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline of the extent of viral evolution.
Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline in the chromosomally integrated viral reservoir.

Full Information

First Posted
February 16, 2010
Last Updated
January 23, 2017
Sponsor
Argos Therapeutics
search

1. Study Identification

Unique Protocol Identification Number
NCT01069809
Brief Title
Safety and Efficacy Study of AGS-004 During Analytical Treatment Interruption
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
July 2010 (Actual)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Argos Therapeutics

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AGS-004
Arm Type
Experimental
Arm Description
HIV-1 Immune Therapy
Arm Title
Inactive Injection
Arm Type
Placebo Comparator
Arm Description
Inactive Placebo Injection
Intervention Type
Biological
Intervention Name(s)
AGS-004
Intervention Description
HIV-1 Immune Therapy
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Inactive Placebo Injection
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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)
Title
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)
Title
Evaluate AGS-004 versus Placebo for change from Baseline in TEAEs, clinical laboratory evaluations, and clinical assessments.
Time Frame
2 years
Title
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)
Title
Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline in T-cell response.
Time Frame
2 years
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and females ≥ 18 to 60 years of age. HIV infection. Stable ART regimen for ≥ 3 months prior to Screening. HIV VL level ≤ 400 copies/mL for ≥ 2 months prior to Screening. HIV VL level ≤ 50 copies/mL at Screening. CD4+ T cell count ≥ 450 cells/mm3 at Screening. Pre-ART nadir CD4+ T cell counts ≥ 200 cells/mm³. Availability of an adequate sample of frozen plasma most recently collected (no more than 90 days and preferably within 30 days) before starting ART. Laboratory values within pre-defined limits at Screening and Eligibility. 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. 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: HIV-2 antibody positive at Screening Visit. Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody (if positive HCV antibody, HCV RNA must be negative). Untreated syphilis infection (positive rapid plasma reagin [RPR]). Changes in ART regimen due to virologic breakthrough. History of lymph node irradiation or dissection. Prior use of any HIV immunotherapy or vaccine within 9 months prior to Screening. Prior participation in an AGS-004 clinical study. Treatment interruption of ART for > 1 month since starting the ART from which the pre-ART plasma sample was drawn. Any acute infection or medical illness within 14 days prior to Screening and throughout the pre-treatment evaluation phase (Step 1). 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). Pregnancy or breast-feeding. Receipt of any immune modulators or suppressors within 30 days prior to Screening and throughout the pre-treatment evaluation phase (Step 1). 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. 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. 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. Prior history of an acquired immunodeficiency syndrome (AIDS) defining condition. 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. Known allergy or sensitivity to the components of the investigational immunotherapy. Active drug or alcohol use or dependence that would interfere with adherence to study requirements in the opinion of the investigator. Use of systemic corticosteroids and use of topical steroids over a total area exceeding 15 cm² within 30 days prior to Screening. Any investigational antiretroviral agents or use of a CCR5 inhibitor at Screening. Active autoimmune disease or condition. Participation in another investigational clinical study within the previous 30 days or use of investigational agents. Body weight less than 30 kg.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffery Jacobson, MD
Organizational Affiliation
Drexel University
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCDavis Research Office at CARES
City
Sacramento
State/Province
California
ZIP/Postal Code
95811
Country
United States
Facility Name
Jacobi & North Central Bronx Hospitals
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
AIDS Clinical Trials Unit
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Division of Infectious Disease and HIV Medicine Partnership Comprehensive Care Practice
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191002
Country
United States
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 816
Country
Canada
Facility Name
Clinique médicale l'Actuel
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2L4P9
Country
Canada
Facility Name
Clinique Médical du Quartier Latin
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2L5B1
Country
Canada
Facility Name
Montreal Chest Institute, Immunodeficiency Dept.
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X 2P4
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.argostherapeutics.com/
Description
Sponsor Website

Learn more about this trial

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

We'll reach out to this number within 24 hrs