Investigating Immunisation Strategies of DNA, MVA and CN54rgp140 Adjuvanted With GLA-AF to Maximise Antibody Responses

NCT01922284 | Completed Phase 1 DMC

• 2 other identifiers: CRO20592012-003277-26
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

UKHVC Spoke 003 is a randomised Phase I, two centre study which will explore the impact of shortening a vaccination regimen using deoxyribonucleic acid (DNA) (CN54ENV and ZM96GPN), Modified Vaccinia Ankara - C (MVA-C) and CN54rgp140 adjuvanted with glucopyranosyl lipid A adjuvant - aqueous form (GLA-AF). The study population will be 40 healthy male and female volunteers 18 to 45 years old who are at low risk of HIV infection are to be recruited. Study participants will be immunised with trial immunogens:

• 8mg DNA: one plasmid encoding a gag-pol-nef polypeptide derived from the 96ZM651-8 clone and one plasmid encoding gp140 env derived from clade C 97CN54
• 1.108 TCID50 MVA-C (nominal titre) expressing the gag-pol-nef and gp120 env proteins derived from clade-C 97CN54
• 100ug CN54rgp140, a trimeric recombinant envelope protein derived from clade C 97CN54
• 5ug GLA-AF, an aqueous glucopyranosyl lipid A adjuvant All immunisations will be administered by the intramuscular route (IM). CN54gp140 and GLA will be mixed together before administration, and immunogens will be delivered in combination regimens

Conditions

HIV

Keywords

HIV; Vaccine; Immunisation; DNA; Adverse events; MVA-C; GLA-AF; Antibody

Outcome Measures

Primary Outcomes (2)

• Magnitude of antibody response

  Magnitude (reciprocal mean endpoint titre and concentration) of systemic Immunoglobulin G (IgG) binding antibody responses to CN54rgp140 measured four weeks after the final immunisation.

  Four weeks after final immunisation

• Adverse Events

  Grade 3 or above local solicited adverse event Grade 3 or above systemic clinical and laboratory solicited adverse event Any grade of adverse event that results in a clinical decision to discontinue further immunisations

  Every four weeks up to 32 weeks

Secondary Outcomes (5)

• Magnitude of neutralising antibody (Nab) responses

  Four weeks after the final immunisation

• Magnitude of T-cell and B-cell responses

  Four weeks after the final immunisation

• Magnitude of mucosal IgG and IgA antibody responses

  Four weeks after the final immunisation

• Magnitude of antibody-dependent cell-mediated cytotoxicity or Antibody-dependent cell-mediated viral inhibition

  From first immunisation

• Magnitude of systemic Immunoglobulin A (IgA) binding antibody responses

  Four weeks after the final immunisation

Study Arms (2)

Group 1 - Combination arm

EXPERIMENTAL

All participants will receive DNA vaccines at 0,4 and 8 weeks. These will be administered in 2 separate injections of 1ml (CN54ENV into the muscle of the upper right arm and ZM96GPN into the muscle of upper left arm). Participants in group 1 will receive 5 immunisations (DNA, MVA and CN54rgp140 in GLA-AF vaccines) at weeks 0, 4, 8 16 and 20. At weeks 16 and 20, individuals in group 1 will be given MVAC in a volume of 0.5mls into the upper left arm and also 100ug CN54rgp140 mixed with 5ug GLA-AF in a total volume of 0.4mls into the muscle of the upper right arm.

Biological: DNA; Biological: MVA-C; Biological: CN54rgp140; Biological: GLA-AF

Group 2 - Non-combination arm

ACTIVE COMPARATOR

All participants will receive DNA vaccines at 0,4 and 8 weeks. These will be administered in 2 separate injections of 1ml (CN54ENV into the muscle of the upper right arm and ZM96GPN into the muscle of upper left arm). Participants in group 2 will receive 7 immunisations (DNA, MVA and CN54rgp140 in GLA-AF vaccines) at weeks 0, 4, 8, 16, 20, 24 and 28. At weeks 16 \& 20 group 2 will receive only 0.5mls of MVAC into the muscle of the upper left arm. At weeks 24 and 28 they will receive injections of 100ug CN54rgp140 mixed with 5ugGLAAF in a total volume of 0.4mls into the muscle of the upper right arm.

Biological: DNA; Biological: MVA-C; Biological: CN54rgp140; Biological: GLA-AF

Interventions

DNA BIOLOGICAL

8mg DNA: one plasmid encoding a gag-pol-nef polypeptide derived from the 96ZM651-8 clone and one plasmid encoding gp140 env derived from clade C 97CN54

Group 1 - Combination arm; Group 2 - Non-combination arm

MVA-C BIOLOGICAL

1.108 TCID50 MVA-C (nominal titre) expressing the gag-pol-nef and gp120 env proteins derived from clade C 97CN54

Group 1 - Combination arm; Group 2 - Non-combination arm

CN54rgp140 BIOLOGICAL

100ug CN54rgp140, a trimeric recombinant envelope protein derived from clade C 97CN54

Group 1 - Combination arm; Group 2 - Non-combination arm

GLA-AF BIOLOGICAL

5ug GLA-AF, an aqueous glucopyranosyl lipid A adjuvant

Group 1 - Combination arm; Group 2 - Non-combination arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Man or woman aged between 18 and 45 years on the day of screening
• Available for follow-up for the duration of the study (up to \~10 months from enrolment)
• At low risk of HIV and willing to remain so for the duration of the study defined as:
• no history of injecting drug use in the previous ten years
• no gonorrhoea or syphilis in the last six months
• no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months
• no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative
• no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
• Willing to undergo an HIV test
• Willing to undergo a genital infection screen if indicated by sexual history
• If heterosexually active female, using an effective method of contraception with partner other than an IUCD/IUS (combined oral contraceptive pill; injectable or implanted contraceptive; consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination
• If heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination
• Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary
• Registered with a general practitioner (GP) for at least the past three months
• Satisfactory response received from GP before randomisation

You may not qualify if:

• Pregnant or lactating
• Presence of an IUCD (intrauterine contraceptive device)/IUS (intrauterine system)
• Clinically relevant abnormality on history or examination including
• history of grand-mal epilepsy, seizure disorder or any history of prior seizure
• severe eczema
• liver disease with inadequate hepatic function
• any skin condition which may interfere with the trial assessment on the injection site
• haematological, metabolic, gastrointestinal or cardio-pulmonary disorders
• uncontrolled infection; toxic shock syndrome; autoimmune disease, immunodeficiency or use of immunosuppressives in preceding 3 months
• Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
• History of severe local or general reaction to vaccination defined as
• local: extensive, indurated redness and swelling involving the major circumference of the arm, not resolving within 72 hours
• general: fever \>= 39.5°C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
• Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of enrolment
• Receipt of an experimental vaccine containing HIV antigens at any time in the past

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator
• Wellcome Trust: collaborator

Study Sites (2)

Surrey Clinical Research Centre, University of Surrey

Guildford, Surrey, GU2 7XP, United Kingdom

Location

Imperial College London

Greater London, W2 1PG, United Kingdom

Location

MeSH Terms

Interventions

DNA; GLA-AF adjuvant

Intervention Hierarchy (Ancestors)

Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Sheena McCormack, MSc, FRCP

  Senior Clinical Scientist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2013
• First Posted: August 14, 2013
• Study Start: June 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: December 1, 2015
• Last Updated: September 27, 2016

Record last verified: 2013-08

Locations

GB (2)