A phase I/II trial to compare the immunogenicity and safety of three DNA C prime followed by one NYVAC C boost to two DNA C prime followed by two NYVAC C boost

ISRCTN	ISRCTN20946776
DOI	https://doi.org/10.1186/ISRCTN20946776
ClinicalTrials.gov number	NCT00490074
Secondary identifying numbers	EV03 / ANRS Vac20

Submission date: 22/05/2007
Registration date: 29/06/2007
Last edited: 11/04/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=2

Contact information

Dr Sheena McCormack
Scientific

MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom

Phone	+44 (0)20 7670 4708
Email	smc@ctu.mrc.ac.uk

Study information

Study design	Randomised phase I/II multicentre international trial with a parallel group design, open to participants and investigators but blind to laboratory personnel.
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Prevention
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet'
Scientific title	A phase I/II trial to compare the immunogenicity and safety of three DNA C prime followed by one NYVAC C boost to two DNA C prime followed by two NYVAC C boost
Study acronym	EuroVacc 03 / ANRS Vac20
Study objectives	The primary objectives are to compare the immunogenicity and safety of the three DNA-C prime and one NYVAC-C boost regimen to two DNA-C prime and two NYVAC-C boosts in healthy volunteers at low risk of HIV infection.
Ethics approval(s)	UK: 1. Medicines and Healthcare Products Regulatory Agency (MHRA), 09/02/07, ref: 30860/0001/001-001 2. Gene Therapy Advisory Committee (GTAC), 26/02/2007, ref: 131 France: 3. Local ethics approval: Committee for the protection of persons [Comite de Protection des Personnes], 25/04/2007, dossier no. 07-007 4. Approval from French Health Products Safety Agency (Agence Française de Sécurité Sanitaire des Produits de Santé [AFSSAPS]), pending as of 22/05/2007 Switzerland: 5. Local ethics approval: approved by the University of Lausanne (UNIL Universite de Lausanne), ref: 233/06 6. Swiss Federal Authority (Swiss Agency for Therapeutic Products [SWISSMEDIC]), approval pending as of 22/05/2007. Germany: 7. Ethics commission of Regensburg University (Ethik-kommission an der Universität Regensburg), ref: 06/084, approval pending as of 22/05/2007
Health condition(s) or problem(s) studied	HIV prophylaxis
Intervention	Group 1: 3 x DNA HIV-C (2 x 2 ml IntraMuscular [IM] at weeks 0, 4 and 8 in right and left vastus lateralis) followed by NYVAC HIV-C (1 ml IM at week 24 in non-dominant deltoid) Group 2: 2 x DNA HIV-C (2 x 2 ml IM at weeks 0 and 4 in right and left vastus lateralis) followed by 2 x NYVAC HIV-C (1 ml IM at weeks 20 and 24 in non-dominant deltoid)
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	DNA-C prime, NYVAC-C boosts
Primary outcome measure	The primary endpoints are immunogenicity and safety. The primary immunogenicity parameter will be the presence of CD8/CD4+ T-cell responses defined according to internationally agreed criteria for evaluation of interferon-gamma (IFN×) Enzyme-Linked Immunosorbent SPOT (ELISPOT) assays: 1. In response to env peptide plus at least one of the gag, pol, nef peptide pools 2. At weeks 26 and 28 The primary safety parameters will be graded and are: 1. Grade 3 or above local adverse event (pain, cutaneous reactions including induration) 2. Grade 3 or above systemic adverse event (temperature, chills, headache, nausea, vomiting, malaise and myalgia) 3. Grade 3 or above other clinical or laboratory adverse event confirmed at examination or on repeat testing, respectively. 4. Any event attributable to vaccine leading to discontinuation of the immunisation regimen.
Secondary outcome measures	Secondary immunogenicity and safety end-point information will be collected on all participants on the following: 1. Cellular responses: 1.1. CD8/CD4+ T cell mean IFN× Spot Forming Units (SFU) per million cells across the peptide pools at weeks 26 and 28 1.2. CD8/CD4+ T cell mean Spot Forming Units (SFU) per million cells across the peptide pools at any week following the first immunisation including weeks 48 and 72 1.3. Mean proportion of CD4/CD8+ T cells producing IL-2 and/or IFN-× following ex-vivo stimulation with HIV-1 peptide pools at weeks 26 and 28, 48 and 72 1.4. Number of different epitopes that can be characterised 2. Antibody responses: precise assays to be determined at a later stage, but prior to unblinding of laboratory personnel 3. All grade 1 and 2 adverse events 4. All events including those considered unrelated to vaccine
Overall study start date	25/06/2007
Completion date	01/09/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	140
Key inclusion criteria	1. Age between 18 and 55 on the day of screening 2. Available for follow-up for the duration of the study (78 weeks from screening) 3. Able to give written informed consent 4. At low risk of HIV and willing to remain so for the duration of the study 5. Willing to undergo a HIV test 6. Willing to undergo a genital infection screen 7. If heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable contraceptive; IntraUterine Contraceptive Device [IUCD]; 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 8. 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
Key exclusion criteria	1. Pregnant or lactating 2. Clinically relevant abnormality on history or examination including history of: 2.1. Grand-mal epilepsy 2.2. Severe eczema 2.3. Allergy to eggs or gentamicin 2.4. Severe allergic diseases 2.5. Liver disease with inadequate hepatic function 2.6. Haematological, metabolic or gastrointestinal disorders 2.7. Uncontrolled infection 2.8. Autoimmune disease, immunodeficiency or use of immunosuppressives in preceding 3 months 3. Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of enrolment 4. Receipt of blood products or immunoglobin within 4 months of screening 5. Participation in another trial of a medicinal product, completed less than 30 days prior to enrolment 6. History of severe local or general reaction to vaccination 7. HIV 1/2 positive or indeterminate on screening 8. Positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment 9. Positive for DNA/antinuclear (ANA) antibodies at titre considered clinically relevant by immunology laboratory 10. Grade 1 or above routine laboratory parameters 11. Unlikely to comply with protocol
Date of first enrolment	25/06/2007
Date of final enrolment	01/09/2009

Locations

Countries of recruitment

England
France
Germany
Switzerland
United Kingdom

Study participating centre

MRC Clinical Trials Unit

London
NW1 2DA
United Kingdom

Sponsor information

EuroVacc Foundation (Switzerland)
Industry

c/o Prof Peter Liljestrom
Rue de la Grotte 6
Lausanne
1003
Switzerland

Phone	+46 845 72550
Email	peter.liljestrom@mtc.ki.se
Website	http://www.eurovacc.org
"ROR"	https://ror.org/04f2nz275

Funders

Funder type

Government

European Commission (Belgium) (ref: QLK2-CT-2002-01431)
Government organisation / National government

Alternative name(s): European Union, Comisión Europea, Europäische Kommission, EU-Kommissionen, Euroopa Komisjoni, Ευρωπαϊκής Επιτροπής, Европейската комисия, Evropské komise, Commission européenne, Choimisiúin Eorpaigh, Europskoj komisiji, Commissione europea, La Commissione europea, Eiropas Komisiju, Europos Komisijos, Európai Bizottságról, Europese Commissie, Komisja Europejska, Comissão Europeia, Comisia Europeană, Európskej komisii, Evropski komisiji, Euroopan komission, Europeiska kommissionen, EC, EU

French National Agency for AIDS Research (Agence Nationale de Recherches sur le SIDA [ANRS]) (France)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	13/06/2008	26/02/2019	Yes	No

Editorial Notes

11/04/2019: Internal review.
26/02/2019: Publication reference added.
16/03/2017: No publications found in PubMed, verifying study status with principal investigator.