Phase II Study of AGS-004 as an Immunotherapeutic in Antiretroviral Therapy (ART)-Treated Subjects Infected With HIV

A Phase II Study Testing the Activity and Safety of AGS-004 as an Immunotherapeutic in Successfully ART-Treated Subjects Infected With HIV-1 in Combination With ART Followed by ART Interruption

The purpose of this study is to examine the ability of AGS-004 to control HIV-1 replication and to determine if HIV-1 immunotherapy made with dendritic cells is safe and well tolerated, to determine if immunotherapy increases the body's immune response to HIV-1; and, to determine if after stopping anti-HIV drugs, immunotherapy can control the HIV-1 virus.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: AGS-004

Detailed Description

Although chronic ART raises cluster of differentiation CD 4+ T cell counts and improves immune function, the immune systems' ability to control HIV-1 replication is not improved. AGS-004 is an immunotherapeutic agent made from autologous DCs co electroporated with amplified in vitro transcribed (IVT) ribonucleic acid (RNA) encoding CD40L and with IVT RNA encoding three or four autologous HIV-1 antigens. The HIV-1 RNA is derived from the plasma sample taken immediately prior to the initiation of ART.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2R0X7
      • Southern Alberta Clinic
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • Providence Health Care Society / The University of British Columbia / BC Centre for Excellence in HIV/AIDS
  • Ontario
    • Hamilton, Ontario, Canada, L7R3X5
      • Hamilton Health Sciences - McMaster University Medical Centre
    • Ottawa, Ontario, Canada, K1H8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M4N3M5
      • Sunnybrook Health Sciences Center
    • Toronto, Ontario, Canada, M5B 1L6
      • Maple Leaf Clinic
    • Toronto, Ontario, Canada, M5G2C4
      • UHN
  • Quebec
    • Montreal, Quebec, Canada, H2X 2P4
      • Montreal Chest Institute
    • Montreal, Quebec, Canada
      • CHUM
    • Montreal, Quebec, Canada, H2L4P9
      • Clinique Médicale l'Actuel
    • Montreal, Quebec, Canada, H2L5B1
      • Clinique Médical du Quartier Latin
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Practice Comprehensive Care Practice Div of Onfectious Disease & HIV Med

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:

• 18 to 60 years of age
• HIV-1 infection
• Subjects must be on their first ART regimen for at least 3 months: 2 NRTIs together with an NNRTI and/or at least 1 PI (prior changes to ART regimen are allowed if due to tolerability, guideline change, or to simply dosing but not for viral control)
• Durable viral suppression (below limit of detection) for at least 3 months prior ot Screening
• CD4+ T cell count ≥ 450 cells/mm3 for at least 90 days immediately prior to Screening
• Availability of ≥ 1.2 mL of continually frozen plasma (may have been thawed and refrozen only once) drawn no more than 90 days before starting ART and preferably within 30 days.
• Pre-ART plasma HIV-1 RNA levels of ≥ 15,000 copies/mL at the time the plasma was archived before commencing ART
• Pre-ART nadir CD4+ T cell count ≥ 200 cells/mm3 (cell count of < 200 cells/mm3 on one occasion is allowed if subsequent pre-ART CD4+ cell counts were > 200 cells/mm3 on at least two time points.

• Laboratory values obtained at Screening and confirmed just prior to Baseline Day 1:

  • Creatinine ≤ 1.5 x upper limit of normal (ULN);
  • AST (SGOT), ALT (SG'PT), and alkaline phosphatase ≤ 3 x ULN;
  • ANC ≥ 750 cells/mm3;
  • Hemoglobin ≥ 10 g/dL; and,
  • Platelet count ≥ 75,000/mm3
• Female subjects of reproductive potential must have a negative serum or urine pregnancy test with a sensitivity of at most 50 mIU/mL performed within 30 days prior to Screening.
• All subjects must agree not to participate in a conception process and use contraception.
• Ability to communicate effectively with study personnel; considered reliable, willing, and cooperative in terms of compliance with the Protocol requirements.
• Voluntary informed consent given to participate in the study.
• Successful RNA amplification of at least 3 antigens (must include Gag).

Exclusion Criteria:

• HIV-2 antibody positive.

• Positive test for other infectious diseases including:

  • clinically active, untreated syphilis (positive rapid plasma regain test (RPR)
  • clinically active hepatitis B infection (positive Hep B surface antigen HBsAg)
  • active hepatitis C infection or any history of hepatitis C infection
  • positive test for HTLV Type I or Type II antibody
• Any acute infection or serious medical illness within 14 days prior to study entry
• History of lymph node irradiation or dissection
• Pregnancy or breast-feeding
• Previous use of any HIV-1 immunotherapy, including IL-2
• Use of hydroxyurea within 30 days prior to Screening
• Immunodeficiency other than HIV-1 or requirements to take immuno-modulating concomitant medications
• Known allergy or sensitivity to the investigational immunotherapy or its formulation
• Use of systemic corticosteroids and use of topical steroids over a total area exceeding 15 cm2 within 4 weeks of Screening or anticipated need for periodic use of corticosteroids during the study
• Receipt of any immune modulators or suppressors within 30 days of Screening

• Active autoimmune disease such as:

  • Rheumatoid arthritis
  • Inflammatory bowel disease
  • Systemic lupus erythematosis
  • Ankylosing spondylitis
  • Hashimoto's disease
  • Scleroderma
  • Multiple sclerosis
  • Autoimmune hemolytic anemia
  • Immune thrombocytopenic purpura
• Type I diabetes mellitus (insulin therapy for Type II diabetes is permitted)
• Participation in another clinical trial within 30 days of Screening or use of investigational agents (previous use of expanded access ARTs is permitted)
• Body weight less than 30 kg.
• Changes in ART regimen due to virologic failure (not including toxicities)
• Presence of factors predicting insufficient adherence to the protocol.
• Any condition that in the assessment of the investigator would indicate that it is not in the best interest of the subject or incompatible with the any aspect of the study design, treatment plan, and study objectives for a subject to participate.
• History or other evidence of severe illness, malignancy, or any other condition that would make the subject, in the opinion of the investigator, unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Biological: AGS-004; HIV-1 Immune Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ability of AGS-004 therapy to improve immune control of HIV-1 replication	Study Week 26 through end of study

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in plasma HIV-1 RNA set point	Study Week 26 through end of study
T cell responses to AGS-004 therapy and exploratory studies to investigate the mechanism of action of AGS-004.	Study Week 26 through end of study
Safety and tolerability of AGS-004	Study Week 26 through end of study

Collaborators and Investigators

• Sponsor: Argos Therapeutics
• Investigators: Principal Investigator: Jean-Pierre Routy, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre; Principal Investigator: Mona Loutfy, MD, Maple Leaf Clinic; Principal Investigator: Cecile Tremblay, MD, CHUM- Hotel Dieu de Montreal; Principal Investigator: John Gill, MD, Southern Alberta Clinic; Principal Investigator: Jean-Guy Baril, MD, Clinque Medical du Quartier Latin; Principal Investigator: Sylvie Vezina, MD, Clinque medicale l'Actuel; Principal Investigator: Jonathan B Angel, MD, The Ottawa Hospital; Principal Investigator: Sharon Walmsley, MD, UHN; Principal Investigator: Fiona Smaill, MD, Hamilton Health Sciences Corporation; Principal Investigator: Anita Rachlis, MD, Sunnybrook Health Sciences Center; Principal Investigator: Julio Montaner, MD, Providence Health Care Society; Principal Investigator: Jeffrey Jacobson, MD, Partnership Comprehensive Care Practice

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 5, 2008
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (Estimate): May 6, 2008

Study Record Updates

• Last Update Posted (Estimate): January 29, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: HIV; Human immunodeficiency virus; HIV-1; Treatment Experienced; HAART; ART; Immunodeficiency Virus, Human; antiretroviral therapy; highly active retroviral therapy; cluster of differentiation CD 4+ T cell counts; HIV-1 Subjects successfully ART treated
• 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-004-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No