Cervicovaginal Immune Responses to 3 Deltoid or Thigh Intramuscular (IM) TicoVac

NCT01710189 | Completed Phase 4

• 1 other identifier: CRC306
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Many viral infections of global importance, including HIV, are transmitted across the mucosal surface of the genital tract. As immunity against these infections is likely to be primarily mediated by antibodies in mucosal secretions, developing techniques to increase the levels and persistence of antiviral antibody on mucosal surfaces may enhance the protection against a number of important infections. Preclinical studies have anatomically targeted vaccine antigens to sites where genital tract immunity is induced. This response is likely due to the ability of regional lymph Preclinical studies have anatomically targeted vaccine antigens to sites where genital tract immunity is induced. This response is likely due to the ability of regional lymph nodes to "pattern" the cell surface markers of responding vaccine specific lymphocytes with homing markers. In contrast, injecting a distant muscle (such as in the arm) which shares no anatomical relationship with the vagina, may not pattern cells with homing markers for the genital tract. Direct injection of inguinal lymph nodes is impractical in humans but intramuscular injection into the thigh will target antigens to the deep inguinal lymph nodes shared in common with the cervix/vagina. This study will be a Phase IV randomised, single centre, open label, laboratory assessment blinded exploratory trial to assess mucosal immunogenicity following three targeted intramuscular immunisations with TicoVac vaccine. 20 subjects will be randomised to each of2 groups immunised in right deltoid or right anterolateral thigh. Following an initial screening visit subjects will be immunised at 0, 1 and 6 months. There will be follow up visits 5 days after each immunisation and a final visit at 7 months. Blood samples and cervicovaginal secretions will be taken prior to each immunisation for immunological measures. In addition, blood samples will be taken at each immunisation and follow up visit for measurement of peripheral blood mononuclear cells. The study is funded by ADITEC, which is a collaborative research programme that aims to accelerate the development of novel and powerful immunisation technologies for the next generation of human vaccines.

Conditions

Tick-Borne Encephalitis

Keywords

Tick-Borne Encephalitis Virus

Outcome Measures

Primary Outcomes (1)

• Primary: Proportion of subjects with a 15-fold or greater increase from pre-immunisation levels of anti-TBEV IgG in cervico-vaginal secretions at 28 days after final immunisation.

  To determine whether immunisations in the anterolateral right thigh increases the proportion of subjects with a 15-fold or greater increase from pre-immunisation levels of anti-TBEV IgG in cervico-vaginal secretions at 28 days after final immunisation when compared with immunisations in the right arm

  28 weeks

Secondary Outcomes (1)

• Secondary: Proportion of subjects with a 2-fold or greater increase from pre-immunisation levels of anti-TBEV IgA in cervico-vaginal secretions at 28 days after final immunisation

  28 weeks

Study Arms (2)

TicoVac immunisation - right deltoid muscle

EXPERIMENTAL

IM immunisation right deltoid muscle

Drug: TicoVac

TicoVac immunisation - upper anterolateral thigh

EXPERIMENTAL

IM: right upper anterolateral thigh

Drug: TicoVac

Interventions

TicoVac DRUG

Intramuscular immunisation to right deltoid muscle (Group 1) or right upper anterolateral thigh muscle (Group 2).

TicoVac immunisation - right deltoid muscle; TicoVac immunisation - upper anterolateral thigh

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged between 18 and 49 years on the day of screening.
• Available for follow-up for the duration of the study.
• Willing and able to give written informed consent.
• Agree to abstain from donating blood during and for three months after the end of their participation in the trial, or longer if necessary.
• Willing to abstain from vaginal intercourse for 12 hours prior to cervico-vaginal secretions sampling.

You may not qualify if:

• Previous immunisation with a TBEV vaccine or history of TBEV infection.
• Previous immunisation with a Yellow Fever or Japanese B encephalitis vaccine, or history of infection with Yellow fever, Japanese B encephalitis, hepatitis C and dengue infection (as antibodies against these viruses cross react with TBE). Immunisation with Yellow Fever or Japanese B encephalitis vaccine or diagnosis of any of these infections during the study period will exclude the subject.
• Intention to travel to an area requiring immunisation against Japanese B encephalitis within 40 days and yellow fever within 10 days of the expected last visit(as Japanese B encephalitis vaccine requires two immunisations 28 days apart and must be completed within 10 days of departure. Yellow Fever vaccination becomes effective 10 days after a single immunisation)
• Any Intra Uterine Contraceptive Device (as this contraindicates with use of the Softcup).
• Pregnant or lactating at time of screening or immunisations.
• Known hypersensitivity to the vaccine active substance, any of the excipients, or the production residues (formaldehyde, neomycin, gentamicin, protamine sulphate).
• Latex allergy.
• Clinically relevant abnormality on history including uncontrolled infection; autoimmune disease, immunodeficiency, or pre-existing cerebral disorders.
• Any drugs and categories of drugs listed in Appendix 1, by the routes indicated, and at any time during the study period, or for the period preceding screening indicated in Appendix 1.
• Any medications that are not listed in Appendix 1,or any over-the-counter treatments are not excluded.
• Receipt of vaccines other than TBEV vaccines is not excluded. If other injectable vaccines are to be given during the study period, administration should preferably be into different limbs from the study vaccine.
• Receipt of blood products or immunoglobin within 3 months of screening.
• Participation in another trial of a medicinal product, completed less than 90 days prior to visit 2.
• Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
• Unlikely to comply with protocol.

Sponsors & Collaborators

• University of Surrey: lead

Study Sites (1)

Surrey CRC, Egerton Road

Guildford, Surrey, GU2 7XP, United Kingdom

Location

Related Links

• Surrey Clinical Research Centre website

MeSH Terms

Conditions

Encephalitis, Tick-Borne

Condition Hierarchy (Ancestors)

Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Tick-Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Study Officials

• David JM Lewis

  University of Surrey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 19, 2012
• Study Start: October 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: August 3, 2018

Record last verified: 2018-08

Locations

GB (1)