Assessment of VAC-3S Therapeutic Properties When Combined With Standard ART in the Course of HIV-1 Infection

Assessment of VAC-3S Therapeutic Properties When Combined With Standard Antiretroviral Therapy (ART) in the Course of HIV-1 Infection. A European, Randomized, Double Blind Placebo-controlled Phase II Study

The purpose of this study is to evaluate the protective effect of VAC-3S in controlled HIV patients receiving standard of care antiretroviral treatment.

Study Overview

• Status: Unknown
• Conditions: HIV
• Intervention / Treatment: Biological: VAC-3S

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Corbeil-Essonne, France, 91106
    • Hôpital Sud Francilien
  • Lyon, France, 69317
    • Hôpital de La Croix Rousse
  • Montpellier, France, 34295
    • Hôpital Gui de Chauliac
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Paris, France, 75018
    • Hôpital Bichat - Claude Bernard
  • Paris, France, 75012
    • Hôpital Saint-Antoine
  • Paris, France, 75020
    • Hopital Tenon
  • Paris, France, 75013
    • Hopital Pitie Salpetriere
  • Paris, France, 75014
    • Hopital Cochin Saint Vincent De Paul
• Germany
  • Bonn, Germany, 53105
    • Jürgen Rockstroh
  • Köln, Germany, 63225
    • Gerd Fätkenheuer
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic University of Barcelona

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. Documented HIV-1 infection,
2. Adults > 18 and < 60 years of age,
3. Able and willing to comply with the protocol, including availability for all scheduled study visits,
4. Provided a signed written informed consent,
5. Meets study screening physical, medical history and laboratory assessments (defined below),
6. On stable antiretroviral therapy that is consistent with the current standard of care for at least 12 months prior to study screening,
7. Plasma HIV RNA < 50 cps/mL during the previous 12 months,
8. CD4+ T cell count at screening > 200 and < 500 cells/mm3,
9. Adequate hematology, biochemistry, and metabolic blood tests defined as being less than grade 2 according to the Division of AIDS Adverse Events (See Appendix 23.1), except for the numeration of CD4 and for the numeration of lymphocytes,
10. Adequate hepatic and renal function defined as being less than Grade 2 according to the Division of AIDS Adverse Events (See Appendix 23.1),
11. Female patients of childbearing age with one documented negative blood pregnancy tests between Screening and Visit 1/Month 0; Female patient of childbearing potential must be receiving two forms of effective contraception and must be willing to use them throughout the study duration. These include oral, transdermal, systemic or implant contraception birth control, intra-uterine devices (IUD), abstinence and double barrier method such as diaphragm with spermicidal gel or other recommended double barrier method,
12. Affiliated with the National Medical Insurance System,
13. Believed by investigator to be able and willing to comply with the requirements of the study protocol and will be available for all scheduled visits at the study site.

Exclusion Criteria:

1. Not meeting all of the inclusion criteria listed above,
2. Administration of any investigational drug or device within 28 days prior to screening,
3. Prior history of an AIDS-defining event in the past 5 years,
4. Active co-infection with either Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any other active viral hepatitis co-infection,
5. Any acute or clinically significant infections within the past month,
6. Known allergy or intolerance to components of VAC-3S as documented through medical records or via patient interview,
7. Chronic active liver disease as documented by any of the following laboratory assessments: ultrasound, clinical assessment, liver biopsy or equivalent non-invasive methods,
8. Receipt of any known vaccinations within the past 1 month prior to screening,
9. Receipt of any agent in the past 12 months that exerts a known immunological effect (e.g. includes but not limited to IL-2, IL-7, growth hormone…),
10. Patients with Insulin Dependent Diabetes Mellitus, patients receiving anti-diabetic treatment, anticoagulants (excluding daily "baby-dose" aspirin) or daily NSAIDs within one week of study enrollment,
11. Receipt of any contraindicated medications listed in Appendix 23.2,
12. History of or active auto-immune disease,
13. Acute or chronic psychiatric conditions which in the opinion of the investigator would need continual psychological support and/or medications incompatible with study participation,
14. Patients with contraindications to intramuscular injections including, but not limited to, patients with thrombocytopenia and/or anomalies of the coagulation system,
15. Any uncontrolled chronic or acute condition that in the opinion of the investigator would compromise safety of the patient or the ability to properly administer the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: VAC-3S 16µg/administration; VAC-3S 16µg/ml administered every 4 weeks for 3 months followed by 3 maintenance vaccinations every 12 weeks after the third initial vaccination.	Biological: VAC-3S; VAC-3S is administered via intra-muscular route in the arm.
PLACEBO_COMPARATOR: VAC-3S Placebo; VAC-3S placebo administered every 4 weeks for 3 months followed by 3 maintenance vaccinations every 12 weeks after the third initial vaccination.	Biological: VAC-3S; VAC-3S is administered via intra-muscular route in the arm.
ACTIVE_COMPARATOR: VAC-3S 32 µg/administration; VAC-3S 32µg/ml administered every 4 weeks for 3 months followed by 3 maintenance vaccinations every 12 weeks after the third initial vaccination.	Biological: VAC-3S; VAC-3S is administered via intra-muscular route in the arm.
ACTIVE_COMPARATOR: VAC-3S 64 µg/administration; VAC-3S 64µg/ml administered every 4 weeks for 3 months without maintenance vaccination.	Biological: VAC-3S; VAC-3S is administered via intra-muscular route in the arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
anti-3S antibodies titer	From D0 to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tolerance to 6 vaccinations of VAC-3S	safety parameter changes according to the DAIDS (Division of Acquired Immunodeficiency Syndrome) adverse events (AEs) grading table.Safety parameters include adverse events, vital signs, physical examinations, laboratory tests (hematology, blood chemistry, viral load, CD4 and CD8 counts)	From D0 to week 72
blood inflammatory marker concentrations	Inflammatory markers include: Highly sensitive C-reactive protein (hsCRP), Highly sensitive Recombinant human interleukin 6 (hsIL-6), Soluble CD14 (sCD14), Soluble CD163 (sCD163), D-dimer, Interferon (IFN)-gamma inducible protein 10 (IP-10), Tumor necrosis factor receptor 1 (sTNFR1) and 2 (sTNFR2), Immunoglobulin G (IgG),	From D0 to week 72
immunogenic characteristics of VAC-3S	anti-3S antibody titers and determination of anti-3S antibody isotypes and avidity	From D0 to week 72
lymphocyte phenotype markers	Phenotype markers include: Nkp44L expression on the surface of CD4+ T lymphocytes, phenotypic markers of of lymphocyte differentiation and activation	From D0 to week 72
secondary virological effects	3S gp41 sequences and proviral HIV reservoir	From D0 to week 72

Collaborators and Investigators

• Sponsor: InnaVirVax

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ANTICIPATED): November 1, 2016

Study Registration Dates

• First Submitted: November 27, 2013
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (ESTIMATE): January 22, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): June 17, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: IPROTECT1; 2013-002735-23 (EUDRACT_NUMBER)