EuroNeut41: Safety & Immunogenicity of Immunisations With HIV Vaccine

HIV Clinical Trial

Official title:

Phase 1, Randomised, Single-centre, Observer-blind Clinical Trial of Safety and Immunogenicity of Nasal-prime and Intramuscular Boost Immunisation With EN41-FPA2 HIV Vaccine in Healthy Female Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01509144
• Other study ID #: 2010-023693-39
• Status: Completed
• Phase: Phase 1
• First received: January 4, 2012
• Last updated: May 20, 2014
• Start date: January 2012
• Est. completion date: October 2013

Study information

• Verified date: May 2014
• Source: PX'Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: UK: Research Ethic CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

Objectives:

• To assess the safety of three priming immunisations by nasal route followed by two booster immunisations by intramuscular route

• To assess immunogenicity responses induced by the vaccine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: October 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Women aged between 18 and 55 years on the day of screening

2. Available for a maximal study duration of 12/13 months from the inclusion

3. Willing and able to give written informed consent

4. At low risk of HIV infection 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 HIV negative partner

• not had unprotected sex with someone from a region where HIV is more common (e.g Sub-Saharan African, Caribbean, South East Asia) outside a relationship with a regular known HIV negative partner

5. Negative HIV 1/2 antibody/antigen test at screening

6. If heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable or implanted contraceptive; use of condoms incorporating spermicide if using these; physiological or anatomical sterility) from 14 days prior to the first vaccination until 6 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination and blood pregnancy test at screening and final follow up.

7. Agree, to abstain from medications or other agents that are applied via the nasal route from 24 hours prior to each nasal vaccine dosing through to the safety assessment 1week later

8. Agree to abstain from donating blood during their participation in the trial

9. Registered with GP and medical history available for 12 months before dosing

10. Satisfactory response received from General Practitioner relating to medical history before randomization.

Exclusion Criteria:

1. Pregnant or lactating, or planning to get pregnant within the next year

2. Positive alcohol test

3. Positive drugs of abuse test

4. Clinically relevant abnormality on history or examination:

• central nervous system disorder or disease, including

• history of grand-mal epilepsy

• cranial nerve palsies

• severe eczema

• severe epistaxis requiring surgical intervention or blood transfusion

• clinically significant liver disease

• clinically significant haematological, metabolic, gastrointestinal, renal, psychiatric or cardio-pulmonary disorders

• ongoing infection;

• autoimmune disease, immunodeficiency or use of immunosuppressive agents in preceding 3 months prior to dosing

• using inhaled cortico-steroids and intranasal medications

5. Known or suspected history of clinically relevant nasal surgery, injury, nasal polyps or cleft palate, or a condition likely to require regular intranasal medication, which in the opinion of the investigator might interfere with intranasal vaccine administration

6. Known hypersensitivity to any component of the vaccine formulations used in this trial or have severe or multiple allergies

7. History of severe local or general reaction to vaccination defined as

• local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or 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

8. Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of scheduled study vaccine dosing

9. Receipt of an experimental vaccine containing HIV envelope proteins at any time in the past

10. Receipt of blood products or immunoglobin within 4 months of screening

11. Participation in another trial of a medicinal product, completed less than 90 days prior to Visit 2 and planned participation in another clinical trial during the present trial

12. HIV 1/2 antibody/antigen positive or indeterminate on screening

13. Positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment

14. Clinically significant routine laboratory parameters.

15. Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.

16. Unlikely to comply with protocol

17. History of drug or alcohol abuse or regular using of drugs, or who test positive in drugs of abuse and alcohol test at screening or admission

18. Has a condition, or is on regular medication (other than paracetamol, multivitamin, E45, or over the counter remedies) which in the opinion of the investigator is not suitable for participation in the study

19. Any local vaginal, cervical or gynaecological condition which may interfere with collection or interpretation of data collected through vaginal samples.

20. Using any Intra Uterine Contraceptive Device; as there is a risk of dislodging, displacing or removing the device when pulling or removing Softcup used for vaginal sampling.

21. Clinically significant abnormality on ECG performed at the screening visit

22. Any condition that, in the investigator's opinion, compromises the volunteer's ability to meet protocol requirements or to complete the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV

Intervention

Biological:
• EN41-FPA2 HIV vaccine
Group 1 Nasal vaccine - Low-dose (20 µg in 40 µL) IM vaccine (200 µg in 400 µL)
• EN41-FPA2 HIV vaccine
Group 2 Nasal vaccine - Mid-dose (100 µg in 200 µL) IM vaccine (200 µg in 400 µL)
• EN41-FPA2 HIV vaccine
Group 3 Nasal vaccine - Full-dose (200 µg in 400 µL) IM vaccine (200 µg in 400 µL)
• EN41-FPA2 HIV vaccine
Group 4 Nasal Placebo - 400 µL IM vaccine (200 µg in 400 µL)
• Na Cl Placebo vaccine
Group 5 Nasal placebo - 40 µL in Cohort 1 / 200 µL in Cohort 2 IM placebo (400 µL)

Locations

Country	Name	City	State
United Kingdom	Surrey Clinical Research Centre University of Surrey	Guildford	Surrey

Sponsors (2)

Lead Sponsor	Collaborator
PX'Therapeutics	European Commission

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	• Safety of 5 EN41-FPA2 immunisations Primary Endpoints: AEs and IgG and IgA responses to EN41-FPA2	•Safety - Grade 3 or above adverse event. Any grade of adverse event that results in a clinical decision to discontinue further immunisations - Any grade of adverse event that occurs in a volunteer that has received at least one immunisation • Immunogenicity: Proportion of individuals mounting a serum IgG response to EN41-FPA2 at any time point up to 28 days after the final immunisation with 3 fold increase from pre-immunisation baseline sample taken at visit 2, week 0, priming #1. If no serum sample is available at this time point, serum taken at visit 1, screening may be substituted."	up to 28 days after the final immunisation	Yes