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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Biological: AGS-004; Biological: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	38 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	38 weeks
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)	38 weeks (62 weeks for subjects continuing ATI in Step 4)
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)	38 weeks (62 weeks for subjects continuing ATI in Step 4)
Evaluate AGS-004 versus Placebo for change from Baseline in TEAEs, clinical laboratory evaluations, and clinical assessments.	2 years
Evaluate AGS-004 versus Placebo for change in inflammatory markers over treatment period and ATI	38 Weeks (62 weeks for subjects continuing ATI in Step 4)
Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline in T-cell response.	2 years
Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline of the extent of viral evolution.	2 years
Study immunogenicity and mechanism of action by evaluating AGS-004 versus Placebo for change from Baseline in the chromosomally integrated viral reservoir.	2 years

Collaborators and Investigators

• Sponsor: Argos Therapeutics
• Investigators: Principal Investigator: Jeffery Jacobson, MD, Drexel University

Publications and helpful links

Helpful Links

• Sponsor Website

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2010
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: February 16, 2010
• First Submitted That Met QC Criteria: February 16, 2010
• First Posted (Estimate): February 17, 2010

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: AGS-004-003; HHSN266200600019C (Other Identifier: NIH Contract); ES-11702 (Other Identifier: DAIDS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No