Clinical trial NCT00672191: Phase II Study of AGS-004 as an Immunotherapeutic in Antiretroviral Therapy (ART)-Treated Subjects Infected With HIV
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV
Human immunodeficiency virus
Immunodeficiency Virus, Human
HIV-1
ART
antiretroviral therapy
HAART
highly active retroviral therapy
cluster of differentiation CD 4+ T cell counts
HIV-1 Subjects successfully ART treated
Treatment Experienced
Lead sponsor: Argos Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-05-06
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Ability of AGS-004 therapy to improve immune control of HIV-1 replication
timeFrame: Study Week 26 through end of study
Secondary outcomes:
measure: Change in plasma HIV-1 RNA set point
timeFrame: Study Week 26 through end of study
measure: T cell responses to AGS-004 therapy and exploratory studies to investigate the mechanism of action of AGS-004.
timeFrame: Study Week 26 through end of study
measure: Safety and tolerability of AGS-004
timeFrame: Study Week 26 through end of study
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Practice Comprehensive Care Practice Div of Onfectious Disease & HIV Med
state: Pennsylvania
city: Calgary
country: Canada
facility: Southern Alberta Clinic
state: Alberta
city: Vancouver
country: Canada
facility: Providence Health Care Society / The University of British Columbia / BC Centre for Excellence in HIV/AIDS
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - McMaster University Medical Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Clinic
state: Ontario
city: Toronto
country: Canada
facility: UHN
state: Ontario
city: Montreal
country: Canada
facility: Clinique medicale l'Actuel
state: Quebec
city: Montreal
country: Canada
facility: Clinique Medical du Quartier Latin
state: Quebec
city: Montreal
country: Canada
facility: Montreal Chest Institute
state: Quebec
city: Montreal
country: Canada
facility: CHUM
state: Quebec
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Jean-Pierre Routy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maple Leaf Clinic
name: Mona Loutfy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHUM- Hotel Dieu de Montreal
name: Cecile Tremblay, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Southern Alberta Clinic
name: John Gill, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinque Medical du Quartier Latin
name: Jean-Guy Baril, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinque medicale l'Actuel
name: Sylvie Vezina, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Ottawa Hospital
name: Jonathan B Angel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UHN
name: Sharon Walmsley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hamilton Health Sciences Corporation
name: Fiona Smaill, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Center
name: Anita Rachlis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Providence Health Care Society
name: Julio Montaner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Partnership Comprehensive Care Practice
name: Jeffrey Jacobson, MD
role: PRINCIPAL_INVESTIGATOR
References: