Immunogenicity Study of Vacc-4x Versus Placebo in Patients Infected With HIV

A Phase II, Randomized, Double-blind, Multicenter, Immunogenicity Study of Vacc-4x Versus Placebo in Patients Infected With HIV-1 Who Have Maintained an Adequate Response to ART

Current management of HIV infection includes anti-retroviral therapy (ART). ART cannot cure the infection, making it a life-long treatment that requires sustained patient compliance and imposes significant individual and societal financial burdens on healthcare services. Furthermore, ART side effects often require medication that increases the inconveniences and financial burdens of HIV management. Of further concern is the emergence of viruses resistant to ART that can result in treatment failure.

ART-free periods could provide substantial benefit. Vacc-4x is a peptide-based HIV immunotherapy that is proposed for prolongation of ART-free periods. The purpose of this study is to determine whether Vacc-4x immunotherapy can give safe ART-free period.

Study Overview

• Status: Completed
• Conditions: HIV I Infection
• Intervention / Treatment: Drug: Vacc-4x; Drug: Sterile water

Detailed Description

Current management of HIV infection includes anti-retroviral therapy (ART). ART cannot cure the infection, making it a life-long treatment that requires sustained patient compliance and imposes significant individual and societal financial burdens on healthcare services. Furthermore,ART side effects often require medication that increases the inconveniences and financial burdens of HIV management. Of further concern is the emergence of viruses resistant to ART that can result in treatment failure.

ART-free periods could provide substantial benefit. Vacc-4x is a peptide-based HIV immunotherapy that is proposed for prolongation of ART-free periods. The purpose of this study is to determine whether Vacc-4x immunotherapy can give safe ART-free period.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charité Universitätsmedizin Berlin
  • Berlin, Germany, 12157
    • EPIMED GmbH
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg Eppendorf
  • Hamburg, Germany, 20099
    • ifi - Studien und Projekte GmbH, an der Asklepios-Klinik St. George
  • Köln, Germany, 50937
    • Klinik I für Innere Medizin Klinikum Der Universität zu Köln
• Italy
  • Milano, Italy
    • Istituto San Raffaele
• Spain
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08907
    • Unidad de VIH, Hospital de Bellvitge, Calle Feixa Llarga s/n, Hospitalet de Llobregat.
• United Kingdom
  • Brighton, United Kingdom, BN2 1EE
    • Brighton and Sussex University Hospital, HIV/GUM Research, Elton John Centre
  • London, United Kingdom
    • Chelsea and Westminster Hospital
  • London, United Kingdom
    • Harrison Wing St Thomas' Hospital
• United States
  • California
    • Los Angeles, California, United States, 90035
      • UCLA CARE Center
    • Los Angeles, California, United States, 90048-8700
      • Cedars-Sinai Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Division of Infectious Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-55
• HIV positive at least one year
• Clinically stable on ART for at least six months
• Documented viral load less than 50 copies/mL for the last six months
• Documented prestudy CD4 cell count equal or more than 400x10exp6/L
• Nadir CD4 cell count equal or more than 200x10exp6/L
• Signed informed consent

Exclusion Criteria:

• Reported pre-study AIDS-defining illness within the previous year
• Malignant disease
• On chronic treatment with immuno-suppressive therapy
• Unacceptable values of hematology and clinical chemistry parameters
• Current chronic infection such as HCV and HBV or active tuberculosis
• Pregnant or breastfeeding women
• Not using safe contraceptive methods
• Participation in other clinical trial
• Incapability of compliance

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vacc-4x; Vacc-4x reconstituted in sterile water (0.1 mL) at a dose of 1.2mg per intradermal administration. Participants are given a total of 6 immunizations over 18 weeks (weeks 1, 2, 3, 4, 16, 18). Recombinant human granulocyte macrophage colony stimulating factor (rhuGM-CSF) Leukine (0.06mg in 0.1 mL) administered intradermally is used as a local adjuvant.	Drug: Vacc-4x; Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.; Other Names: Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13.
Placebo Comparator: Placebo; Placebo injections consisting of sterile water (0.1 mL) in place of Vacc-4x. Placebo injections consisting of sterile water (0.1 mL) in place of Leukine.	Drug: Sterile water; Sterile water is used in place of Vacc-4x and in place of Leukine; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Subjects Who Require Resumption of ART Between the Interruption of ART at Week 28 and End of Study at Week 52.	From Week 28 to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Treatment Emergent Adverse Event, Related Treatment Emergent Adverse Events and Deaths	Brief summary of treatment emergent adverse events or related treatment emergent events and deaths. The intensity of adverse events was described according to the Division of AIDS table for grading severity of adult and pediatric adverse events, 2004.	Up to week 52
Immunogenicity	Immunogenicity of Vacc-4x evaluated by DTH (Delayed-type Hypersensitivity) reaction. The number of participants showing induration and/or erythema	Week 1, week 18 and week 52
Effect of Vacc-4x on CD8 Counts	CD8 Count Over Time for subjects who stopped ART at Week 28 and remained off ART until Week 52	Weeks 6,18,24,28,32,36,40,44,48,52.
Time to Restart of ART for Vacc-4x Subjects Versus Placebo	Kaplan-Meier Estimate of Time to restart ART (from time coming off ART)	Between Week 28 to Week 52
Effects on Vacc-4x on HIV-1 RNA		Weeks 24,28,32,36,40,44,48,52.

Collaborators and Investigators

• Sponsor: Bionor Immuno AS
• Investigators: Principal Investigator: Richard Pollard, MD, University of California at Davis, USA; Principal Investigator: Jürgen Rochstroh, MD, Universitätsklinikum Bonn, Germany

Publications and helpful links

General Publications

• Pollard RB, Rockstroh JK, Pantaleo G, Asmuth DM, Peters B, Lazzarin A, Garcia F, Ellefsen K, Podzamczer D, van Lunzen J, Arasteh K, Schurmann D, Clotet B, Hardy WD, Mitsuyasu R, Moyle G, Plettenberg A, Fisher M, Fatkenheuer G, Fischl M, Taiwo B, Baksaas I, Jolliffe D, Persson S, Jelmert O, Hovden AO, Sommerfelt MA, Wendel-Hansen V, Sorensen B. Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2014 Apr;14(4):291-300. doi: 10.1016/S1473-3099(13)70343-8. Epub 2014 Feb 11.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 14, 2008
• First Submitted That Met QC Criteria: April 15, 2008
• First Posted (Estimate): April 16, 2008

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 5, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: CT-BI Vacc-4x 2007/1; 13619 (Other Identifier: FDA IND); 2007-006302-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Participants have not provided informed consent for their anonymized individual data to be made available beyond that described in the patient information sheet.