Condition category
Infections and Infestations
Date applied
13/08/2008
Date assigned
10/10/2008
Last edited
08/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Muhammad Bakari

ORCID ID

Contact details

Muhimbili University of Health and Allied Sciences (MUHAS)
PO Box 65001
Dar es Salaam
-
Tanzania
+255 (0)2153027
mbakari@muhas.ac.tz

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Version 4

Study information

Scientific title

A phase I/II trial to assess the safety and immunogenicity of a plasmid DNA-MVA prime boost HIV-1 vaccine candidate among volunteers in Dar es Salaam, Tanzania

Acronym

HIVIS 03

Study hypothesis

Delivery of plasmid DNA containing HIV-1 genes boosted with a pox vector (MVA) with analogous genes is safe and immunogenic among healthy Tanzanian volunteers.

Ethics approval

1. Research and Publications Committee of the Muhimbili University of Health and Allied Sciences (MUHAS). The study was approved on the 26/04/2006 (ref: MU/RP/AEC/Vol.V/76). As of 19/08/2008, the last amendments were approved on 19/06/2008 (ref: MU/DRP/PA/Vol. I/37)
2. National Ethics Committee at the National Institute for Medical Research (NIMR). The study was approved on 30/01/2006 (ref: NIMR/HQ/R.8a Vol.IX/410). As of 19/08/2008, the last amendments were approved on 19/06/2008 (ref: MU/DRP/PA/ Vol.I/37)

Study design

Randomised double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet (in English and Swahili)

Condition

HIV-1

Intervention

The clinical staff and participants are blinded throughout the trial. The immunological laboratory is blinded during the study.

Priming injections: Injections of seven plasmids containing HIV-1 env subtype A, B and C, gag subtype A and B, RTmut and rev subtype B.

The participants were randomly allocated to the following four arms:
Arm I (n = 20): DNA 3.8 mg (intramuscular [IM])
Arm II (n = 20): DNA 1.0 mg (intradermal [ID])
Arm IIIa (n = 10): saline placebo IM
Arm IIIb (n = 10): saline placebo ID

All injections were administered with the Bioject® device. The env and rev plasmids were injected in the left deltoid muscle and the gag and RT plasmids in the right deltoid muscle. Injections were given at month 0, 1 and 3.

Boost injections: One MVA-CMDR given as an IM or ID injection (with needle and syringe) at a dose of 10^8 pfu in the left deltoid muscle. The MVA contains analogous HIV-1 genes from subtype A/E. It will be given 6 months after the last DNA/placebo injection.

The second MVA boost is planned to be given at 80 weeks (6 months after the first MVA boost). The participants will be formally re-recruited for the second MVA boost. This phase of study will be funded by the European and Developing Countries Clinical Trials Partnership (EDCTP), under the TAMOVAC-I Project.

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

1. Safety:
1.1. Samples for routine biochemistry and haematology (see inclusion criteria) were obtained at screening, before and 2 weeks after each immunisation, and 3 month after the last DNA and MVA immunisation
1.2. 12-lead electrocardiograms were performed before and 2 weeks after the MVA injection
1.3. Clinical adverse reactions and vital signs at 10 and 30 minutes, in addition a contact was made by telephone 1-3 days after each injection
1.4. A 7-day diary card (including standardised measurements of body temperature) was filled in and presented at the visit 2 weeks after each injection, when direct questions were asked on the basis of the diary card
2. Specific reactivity to HIV-1 peptides in IFN-gamma enzyme-linked immunosorbent spot (ELISpot), performed on fresh peripheral blood mononuclear cell (PBMC) before the first DNA and the MVA immunisation and 2 weeks after the last DNA and MVA immunisation

Secondary outcome measures

1. The following will be performed on fresh PBMC before the first DNA and the MVA immunisation and 2 weeks after the last DNA and MVA immunisation:
1.1. Specific reactivity to HIV-1 peptides in IL-2 ELISpot
1.2. Lymphoproliferation to inactivated whole HIV-1 virions
2. A qualitative and quantitative presence of necessary infrastructure and human capacity to conduct HIV-related vaccine studies at MUHAS

Overall trial start date

20/02/2007

Overall trial end date

31/12/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Both males and females, age: 18 to 40 years
2. Willing to undergo counselling and HIV testing
3. Have a negative antigen/antibody ELISA for HIV infection
4. Able to give informed consent
5. Literacy corresponding to a minimum of 7 years of primary education
6. Resident in Dar es Salaam, and willing to remain so for the duration of the study
7. At low risk of HIV infection, defined as the absence of an identifiable risk factor/ behaviour:
7.1. Sexual partner with HIV
7.2. Sexual partner with unknown HIV serostatus who is also unwilling to use protective condoms consistently in all sexual relations
7.3. Sexual partner is known to be at high risk for HIV
7.4. More than one sexual partner in the last 6 months
7.5. History of being an alcoholic (as medically defined or more than 35 units /week)
7.6. History of STI within the past 6 months
8. Verbal assurances that adequate birth control measures are used not to conceive/father a child during the study and up to 4 months after the last vaccine injection
9. Have a negative urinary pregnancy test
10. Be willing to practice safe sex for the duration of the study to avoid sexually transmitted infections including HIV.
11. Good health as determined by medical history, physical examination, clinical judgment and by key laboratory parameters (reference ranges are in accordance with data generated at MUHAS for haematology values, and that generated at Mbeya (MMRP) for biochemical parameters. Exclusion by presence of Diabetes mellitus will be based on the WHO cut-off value of a fasting blood glucose <7.8 mmol/l). Hence no grade 1 or higher routine laboratory parameters, defined as:
11.1. Hb >10.5g/dl
11.2. White blood cell count >1,300/mm^3
11.3. Granulocytes >6.4/mm^3
11.4. Lymphocytes >1.0/mm^3
11.5. Platelets >120,000/mm^3
11.6. CD4 >400 cells/mm^3
11.7. Random blood glucose 2.5-7.0 mmol/L; if elevated, then a fasting blood glucose <7.8 mmol/l
11.8. Bilirubin <1.25 x upper limit of normal (ULN)
11.9.ALT <1.25 x ULN
11.10. Creatinine <1.25 x ULN
11.11. Urine dipstick for protein and blood: negative or trace. (If either is >=1+, obtain complete urinalysis (UA). If microscopic UA confirms evidence of haematuria or if proteinuria >=1+, the volunteer is ineligible)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

1. Active tuberculosis or other systemic infectious process elicited by review of systems, physical examination and laboratory detection, such as detection of Hepatitis B surface antigen, or active syphilis
2. Have a history of immunodeficiency, chronic illness requiring continuous or frequent medical intervention
3. Autoimmune disease by history and physical examination
4. Severe eczema
5. Have a history of psychiatric, medical and/or substance abuse problems during the past 6 months that the investigator believes would adversely affect the volunteer's ability to participate in the trial.
6. History of grand-mal epilepsy, or currently taking anti-epileptics
7. Have received blood or blood products or immunoglobulins in the past 3 months
8. Are receiving immunosuppressive therapy such as systemic corticosteroids or cancer chemotherapy.
9. Have used experimental therapeutic agents within 30 days of study entry
10. Have received any live, attenuated vaccine within 60 days of study entry. (Note: Medically indicated subunit or killed vaccines {e.g., hepatitis A or hepatitis B] are not exclusionary but should be given at least 2 weeks before or after HIV immunisation to avoid potential confusion of adverse reactions)
11. Have previously received an HIV candidate vaccine
12. History of severe local or general reaction to vaccination defined as:
12.1. Local: Extensive, indurated redness and swelling involving most of the major circumference of the arm, not resolving within 72 hours
12.2. General: Fever >=39.5°C within 48 hours, anaphylaxis, bronchospasm, laryngeal oedema, collapse, convulsions or encephalopathy within 72 hours
13. Are lactating mothers
14. Are study site employees who are involved in the protocol and may have direct access to the immunogenicity results
15. Unlikely to comply with protocol as judged by the principal investigator or his designate

Recruitment start date

20/02/2007

Recruitment end date

31/12/2009

Locations

Countries of recruitment

Tanzania

Trial participating centre

Muhimbili University of Health and Allied Sciences (MUHAS)
Dar es Salaam
-
Tanzania

Sponsor information

Organisation

Swedish Institute for Infectious Disease Control (SMI) (Sweden)

Sponsor details

Nobelsväg 18
Solna
17182
Sweden
+46 (0)8457 2635
britta.wahren@smi.ki.se

Sponsor type

Government

Website

http://www.smittskyddsinstitutet.se/in-english

Organisation

Muhimbili University of Health and Allied Sciences (MUHAS) (Tanzania)

Sponsor details

PO Box 65001
United Nations Road
Upanga
Dar es Salaam
-
Tanzania
+255 (0)2150302
vc@muhas.ac.tz

Sponsor type

University/education

Website

http://www.muhas.ac.tz

Funders

Funder type

Other

Funder name

European Union (Belgium)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Swedish International Development Agency (Sida/SAREC) (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Swedish Embassy in Tanzania through the Government of the United Republic of Tanzania (Tanzania)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

MVA was donated by the National Institute of Allergy and Infectious Diseases (NIAID) through Walter Reed Army Institute for Research (WRAIR) (USA) to the Swedish Institute for Infectious Diseases Control (SMI) and subsequently made available to the Muhimbili University of Health and Allied Sciences (MUHAS) (Tanzania)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

European and Developing Countries Clinical Trials Partnership (EDCTP)

Alternative name(s)

EDCTP

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

Netherlands

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24321091
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25874723

Publication citations

  1. Results

    Bakari M, Munseri P, Francis J, Aris E, Moshiro C, Siyame D, Janabi M, Ngatoluwa M, Aboud S, Lyamuya E, Sandström E, Mhalu F, Experiences on recruitment and retention of volunteers in the first HIV vaccine trial in Dar es Salam, Tanzania - the phase I/II HIVIS 03 trial., BMC Public Health, 2013, 13, 1149, doi: 10.1186/1471-2458-13-1149.

  2. Results

    Joachim A, Nilsson C, Aboud S, Bakari M, Lyamuya EF, Robb ML, Marovich MA, Earl P, Moss B, Ochsenbauer C, Wahren B, Mhalu F, Sandström E, Biberfeld G, Ferrari G, Polonis VR, Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults, PLoS One, 2015 , 10, 4, e0118486, doi: 10.1371/journal.pone.0118486.

Additional files

Editorial Notes

08/04/2016: Publication reference added.