A Safety and Immunogenicity Study of 3 Doses of Opal Immunotherapy in HIV Infected People

NCT01123915 | Terminated Phase 1 DMC

• 2 other identifiers: Opal-HIV-10012008-005142-23
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I study is the first step to determine if Opal immunotherapy may have potential utility as a treatment for HIV. Although effective treatments for HIV infection exist, they are limited by the requirement for life-long daily treatment, cost, side effects, and the development of resistance. There is a need for therapeutic approaches that induce or enhance T-cell immunity to control HIV disease. Overlapping Peptide-pulsed Autologous Cells (Opal) is a technique where autologous peripheral blood mononuclear cells (PBMC) or whole blood is pulsed with sets of overlapping peptides spanning whole proteins of HIV.

Conditions

HIV Infections

Keywords

HIV; Therapeutic; Immunotherapy; Acquired Immunodeficiency Syndrome; Virus Diseases; Lentivirus Infections; Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (1)

• Safety

  Examined through treatment-emergent adverse events, vital signs and routine laboratory screening.

  Several points throughout the 12 week active phase and 12 week and follow up period

Secondary Outcomes (2)

• Immunogenicity

  Several points throughout the 12 week active phase and 12 week and follow up period

• Impact on HIV infection

  Several points throughout the 12 week active phase and 12 week and follow up period

Study Arms (2)

Opal-HIV-Gag(c)

EXPERIMENTAL

Opal-HIV-Gag(c) administered ex vivo to separated white blood cells on 4 occasions at 4 weekly intervals.

Biological: Opal-HIV-Gag(c) Low Dose; Biological: Opal-HIV-Gag(c) Medium dose; Biological: Opal-HIV-Gag(c) High dose

Diluent

PLACEBO COMPARATOR

Administered ex vivo to separated white blood cells on 4 occasions at 4 weekly intervals.

Other: Dimethyl Sulfoxide

Interventions

Opal-HIV-Gag(c) Low Dose BIOLOGICAL

Opal-HIV-Gag(c)

Opal-HIV-Gag(c) Medium dose BIOLOGICAL

Opal-HIV-Gag(c)

Opal-HIV-Gag(c) High dose BIOLOGICAL

Opal-HIV-Gag(c)

Dimethyl Sulfoxide OTHER

Diluent

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of written informed consent
• Documented laboratory diagnosis of HIV 1 infection
• Documented HIV clade of infection
• years of age, inclusive
• Stable antiretroviral therapy (ART) regimen containing at least 3 active ART agents for at least 2 months prior to Baseline
• Plasma HIV-Ribonucelc acid (RNA) \<400 copies/millilitre (mL) for 6 months up to and including Screening. Subjects on stable ART with a single value ≥400 copies/mL (i.e. the result is unconfirmed by subsequent testing) within this timeframe may be included at the discretion of the Investigator
• CD4+ T-cell count ≥350 cells/cubic millimetres (mm3) at Screening (with nadir ≥100 cells/mm3)
• A positive immunogenic response when stimulated with HIV-1 Gag clade C peptides at Screening
• Male or female. Women of child-bearing potential must be using two effective methods of contraception and agree to continue to do so from Screening, throughout study medication dosing and for 28 days after the last dose of study medication

You may not qualify if:

• Any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with treatment, assessment, compliance with the protocol, or subject safety. This would include any active clinically significant renal, cardiac, pulmonary, vascular, or metabolic (thyroid disorders, adrenal disease) illness, or malignancy
• Hepatitis B virus surface antigen, or Hepatitis C virus (HCV) antibody and HCV-RNA positive at Screening
• Female subjects who are lactating and those of reproductive potential with a positive urine pregnancy test at either Screening or Baseline
• A new AIDS-defining condition diagnosed within 42 days prior to Baseline visit
• Known or suspected allergy to Dimethyl Sulfoxide
• History of allergy or reaction to medications (including peptide or protein containing agents) or history of severe allergy that, in the opinion of the Investigator, might compromise the subject's participation in any way
• Moderate or severe asthma, defined as at least chronic moderate symptoms which frequently interfere with daily activities and require anti-asthma/anti-inflammatory agents
• Have received immunomodulating agents (including immunosuppressive agents, interferon or other immune or cytokine-based therapies), immunisation, and/or systemic chemotherapeutic agents within 60 days of Screening or expected to receive these agents during the course of the study
• Recipient of live attenuated vaccines within 60 days of Screening
• Recipient of whole killed, toxoid or sub-unit vaccines (e.g. influenza, pneumococcus, tetanus, hepatitis B) within 42 days prior to Baseline
• Ever received an HIV prophylactic or immunotherapeutic vaccine (does not apply to subjects who have written documentation of receiving placebo or adjuvant only)
• Recreational and/or therapeutic drug or alcohol use that, in the opinion of the Investigator, might compromise the subject's participation in any way.
• Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the protocol
• Laboratory blood values:
• Haemoglobin \<11.0 grams/decilitre (g/dL) for men and \<10.0 g/dL for women

Sponsors & Collaborators

• Medicines Development for Global Health: lead
• Phillip T. and Susan M. Ragon Foundation: collaborator
• Imperial College London: collaborator

Study Sites (1)

St Stephen's Centre, Chelsea and Westminster Foundation Trust

London, SW10 9NH, United Kingdom

Location

Related Publications (2)

• Kloverpris HN, Jackson A, Handley A, Hayes P, Gilmour J, Riddell L, Chen F, Atkins M, Boffito M, Walker BD, Ackland J, Sullivan M, Goulder P. Non-immunogenicity of overlapping gag peptides pulsed on autologous cells after vaccination of HIV infected individuals. PLoS One. 2013 Oct 4;8(10):e74389. doi: 10.1371/journal.pone.0074389. eCollection 2013.

  PMID: 24124451 DERIVED

• Jackson A, Kloverpris HN, Boffito M, Handley A, Atkins M, Hayes P, Gilmour J, Riddel L, Chen F, Bailey-Tippets M, Walker B, Ackland J, Sullivan M, Goulder P. A randomised, placebo-controlled, first-in-human study of a novel clade C therapeutic peptide vaccine administered ex vivo to autologous white blood cells in HIV infected individuals. PLoS One. 2013 Sep 17;8(9):e73765. doi: 10.1371/journal.pone.0073765. eCollection 2013.

  PMID: 24069230 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; Virus Diseases; Lentivirus Infections

Interventions

Dimethyl Sulfoxide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Sulfoxides; Sulfur Compounds; Organic Chemicals

Study Officials

• Marta Boffito, MD PhD

  St Stephen's AIDS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2010
• First Posted: May 14, 2010
• Study Start: May 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: March 22, 2018

Record last verified: 2011-11

Locations

GB (1)