NIMR - Mbeya Medical Research Programme

Quick Information

NIMR - Mbeya Medical
Research Center

P.O Box 2410
Hospital Hill rd, Mbeya Tanzania

Tel    +255 25 250 3364
Fax   +255 25 250 3134
Working hours:
Mon   -  Fri
08:00 - 16:30 EAT (GMT + 3)

Vaccine Trials

ALISA (ANRS 12221)

“A multicentre phase III trial of second-line antiretroviral treatment strategies in African adults (Tanzania and South Africa): The ALISA Trial”

Team

Issakwisa Mwakyula (Principal Investigator), Tessa Lennemann, Arne Kroidl (Clinical Research Coordinator)

Purpose

The ALISA Trial is a second line antiretroviral treatment study

The ALISA trial is a phase III , multicentre, non-inferiority, randomized, non-blinded second line antiretroviral treatment study evaluating the virological response (plasma HIV RNA<50 copies/ml) at 48 weeks of two antiretroviral treatment regimens in HIV-1-infected patients with treatment failure after first line antiretroviral therapy.

The primary objective is to demonstrate the non-inferiority of a generic Lamivudine-Tenofovir-Atazanavir/Ritonavir regimen as compared to a standard Emtricitabine-Eenofovir-Lopinavir/Ritonavir regimen after failing first line antiretroviral treatment including a non nucleoside reverse transcriptase inhibitor at 48 weeks.

Overall 386 HIV infected patients on failing first line antiretroviral therapy defined as confirmed virological failure >1000 copies/ml will be 1:1 randomized into one of the treatment arms.

The Mbeya Referral Hospital (MRH) supported by MMRC will participate in the trial enrolling 193 participants.  The trial is expected to provide capacity building for the MRH clinics and laboratories as well as for the Tanzanian Southern Highlands HIV Programme in terms of HIV viral load monitoring and genotypic resistance testing. The trial is expected to start in August 2011.

Sponsor

The ALISA Study is funded by the European and Developing Countries Clinical Trials Partnership Programme (EDCTP) sponsored by the French Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS)

 

Partners

- NIMR-Mbeya Medical Research Center (MMRC) in collaboration with the Mbeya Referral Hospital (MRH) Mbeya, Tanzania

- University of Limpopo Medunsa Campus in Pretoria, South Africa.

- University of Montpellier, France

- University of Munich, Munich, Germany

- Institute of Tropical Medicine in Antwerp/Belgium

- University of Geneva/MSF

The LMU Department of Infectious Diseases and Tropical Medicine participate in this trial providing study coordination and management of the laboratory services. Logistical support is provided through the Munich office within the NIMR-MMRC collaboration.

 

 

 

RV 262

“A Phase I Study of the Safety and Immunogenicity of PENNVAX™-G DNA (Env & Gag) Administered by Intramuscular Biojector® 2000 or by CELLECTRA® Intramuscular Electroporation Device Followed by MVA-CMDR (HIV-1 CM235 env/ CM240 gag/pol) Boost in Healthy, HIV Uninfected Adults”.

Team
Leonard Maboko (Principal Investigator), Arne Kroidl, Philip Mann, Bahati Kaluwa (Clinical Research Coordinator)

Purpose

RV262 is a phase I HIV vaccine trial to evaluate the safety and tolerability of the DNA vaccine candidates administered either by IM Biojector® 2000 injection or IM CELLECTRA® Electroporation followed by an IM MVA vector boost in healthy HIV-uninfected adult participants. The secondary objective is to evaluate the ability of the DNA/MVA prime/boost strategy to induce HIV antigen specific cellular and humoral immune responses.

Approach

The study consists of two parts:

Part A is an open-label, safety and tolerability study to be conducted at one clinical site at the Rockville Vaccine Assessment Clinic (RVAC), USA in 12 healthy, HIV-uninfected adult volunteers. Participants are randomized 1:1 to either the Biojector of the Electroporation delivery group. This part started in October 2010.

Part B is a randomized, placebo-controlled, double blind study to start after the product has been assessed as safe and tolerable in Part A. Part B will be conducted at three East African sites in Kenya, Uganda and Mbeya, Tanzania as well as in one site in Thailand enrolling overall 80 healthy, HIV negative. Low risk volunteers. Participants will be randomized 4:1 to active study drug versus placebo. This part is expected to start in July 2011. The NIMR Mbeya Medical Research Center (MMRC) in Tanzania will participate in the trial enrolling 20 participants.
The vaccine candidates are the PENNVAX™-G DNA (HIV-1 env A, C and D, and consensus gag plasmids) and MVA-CMDR Live attenuated Modified Vaccinia Ankara vector expressing HIV-1 CM235 env/ CM240 gag/pol. PENNVAX™-G DNA priming will be performed at months 0 and 1, MVA-CMDR boosting at months 3 and 6 of the vaccination schedule.

The Biojector® 2000 needle-free injection device delivers the study agent under pressure through a micro-orifice at high velocity using a compressed carbon dioxide cartridge.

Electroporation (EP) uses a needle to deliver the study agent intramuscular associated with short electric impulses. This delivery method is thought to increase the transfection of DNA into antigen-presenting cells (APCs) by creating transient pores in the cell membranes as well as to create mild tissue damage recruiting APCs locally and initiate an inflammatory response thus creating an adjuvant effect.

Sponsor

U.S. Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Health (NIH)

Partners

The trial will be lead by the Walter Reed Army Institute of Research (WRAIR) and the U.S. Military HIV Research Program (MHRP). The study site partners are the:

U.S. Army Medical Research Unit-Kenya and Kenya Medical Research Institute in Kericho, Kenya

Makerere University-Walter Reed Project in Kampala,Uganda,

NIMR-Mbeya Medical Research Center (MMRC) in Mbeya,Tanzania

Armed Forces Research Institute of Medical Services (AFRIMS) in Bangkok, Thailand

The LMU Department of Infectious Diseases and Tropical Medicine participate in this trial providing study coordination and management of the laboratory and immunology services. Logistical support is provided through the Munich office within the NIMR-MMRC collaboration.

 

 

 

TaMoVaC I

 

TaMoVac I: “A Phase I/II trial to assess safety and immunogenicity of ID DNA priming and IM MVA boosting in healthy volunteers in Tanzania and to develop further HIV vaccine trial capacity building in Tanzania.”

 

Team

Leonard Maboko (Principal Investigator), Arne Kroidl, Bahati Kaluwa, Philip Mann (Clinical Research Coordinator)

Purpose

The TaMoVac I study is following the HIVIS 03 (HIV Vaccine Immunogenicity Study) phase I HIV vaccine trial which was led by the Karolinska Institute in Sweden and which took place at the Muhimbili University of Health and Allied Science (MUHAS) in Dar es Salaam. The trial evaluated the safety and immunogenicity of multiclade (A, B, C) plasmid-DNA priming, heterologous MVA-CMDR (CRF01A_E) boosted vaccine regime comparing clinical and immunological endpoint between IM versus ID delivery of the DNA vaccine candidate.

TaMoVac I is a randomized, controlled, double blinded study enrolling 120 healthy, HIV negative, low risk volunteers from MMRC/Mbeya and MUHAS/Dar es Salaam, Tanzania. The objectives of the TaMoVac I trial are to determine the safety and immunogenicity of the HIVIS-DNA at a dose of 600 µg or 1000 µg delivered ID in combined or separate plasmid pools followed by IM MVA-CMDR boost.

Approach

Volunteers are randomized into three different DNA dosing groups (600 µg combined plasmid pool, 600 µg separated plasmid pool, 1000 µg separated plasmid pool) in a vaccine/placebo ratio of 9:1.

The HIV-1 DNA encodes the following genes:

1. Pool 1

a. env, from HIV-1 subtypes A, B, C

b. rev, from HIV-1 subtype B

2. Pool  2

a. gag, from HIV-1 subtypes A, B

b. RTmut (enzymatically inactive mutated reverse transcriptase), from HIV-1 subtype B

Boosting is effected by a Modified Vaccinia Ankara vaccine (MVA-CMDR) which is an attenuated recombinant poxvirus vector expressing the following HIV-1 genes:

1. gp150 (Subtype E, CM235)

2. gag and pol (integrase-deleted and reverse transcriptase non functional, Subtype A, CM240).

DNA priming is performed at weeks 0, 4 and 12 followed by MVA boosting at weeks 30 and 46. The total follow-up period is 84 weeks.

Study Status

Study enrolment in Mbeya started in June 2010 and was closed having enrolled 60 participants in October 2010. MVA vaccinations started in January 2011. The last study visits are expected to be done in December 2011.

Sponsor

The TaMoVac I Trial is funded by the European and Developing Countries Clinical Trials Partnership Programme (EDCTP). The Muhimbili University of Health and Allied Science (MUHAS) act as the Sponsor in collaboration with the Swedish Institute for Infectious Disease Control (SMI)

Partners

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

- NIMR-Mbeya Medical Research Center (MMRC), Mbeya, Tanzania

- National Institute for Medical Research (NIMR), Tanzania

- Central Hospital, Maputo, Mozambique

- Instituto Nacional de Saude (NIH), Mozambique

- Karolinska Institute (KI), Stockholm, Sweden

- Swedish Institute for Infectious Disease Control (SMI), Solna, Sweden

- University of Munich, Munich, Germany

- Imperial College of Science, Technology & Medicine, London, UK

- Medical Research Council Clinical Trial Unit (MRC CTU), London, UK

- Walter Reed Army Institute of Research (WRAIR), U.S. Military HIV Research Program (MHRP), Rockville, USA

The LMU Department of Infectious Diseases and Tropical Medicine participate in this trial providing study coordination, data base development and data management as well as management of the laboratory and immunology services. Logistical support is provided through the Munich office within the NIMR-MMRC collaboration.

 

 

 

RV 172

“A phase I/II clinical trial to evaluate the safety and immunogenicity of a multiclade HIV-1 DNA plasmid vaccine boosted by a multiclade HIV-1 recombinant adenovirus-5 vector vaccine in HIV uninfected adult volunteers in East Africa”

Team: Leonard Maboko (Principal Investigator), Mirjam Schunk, Arne Kroidl (Clinical Research Coordinator)

Purpose

The objectives of the study were to evaluate the safety and immunogenicity of a multiclade A, B and C HIV DNA prime (VRC-HIVDNA016-00-VP) boosted with a multiclade A, B and C recombinant Adenovirus type 5 vector (VRC-HIVADV014-00-VP). The vaccine was provided by the NIH Vaccine Research Center (VRC) consisting of a multiclade A, B and C HIV DNA prime (VRC-HIVDNA016-00-VP) boosted with a multiclade A, B and C recombinant Adenovirus type 5 vector (VRC-HIVADV014-00-VP).

TREATMENT (Vaccine/Placebo) IMMUNIZATION SCHEDULE

Immunization schedule RV 172

Approach

Overall 324 HIV uninfected, low risk adult volunteers were enrolled from three East African study sites (Uganda, Kenya, Tanzania). Study participants attended 14 scheduled study visits over a period of 12 months.  The DNA vaccine was administered by Biojector® 2000 needle-free injection device at weeks 0, 4 and 8, with Ad5 boosting at week 24 in a 1:1 ratio of placebo to vaccine.

MMRC participated in the phase II part of the study enrolling 60 participants. This was the first HIV vaccine trial conducted in Tanzania introducing high levels of community engagement and outreach activities as well as quality control, monitoring and reporting requirements according to international standards for IND trials at the MMRC study site.

Results

Enrollment in Mbeya started in June 2006 and was closed with 60 participants (60% females) in October 2006. During the screening period 491 persons attended briefing session and 280 volunteers were screened leading to a briefing/screening/enrolment ratio of 8:5:1. The last study visit at MMRC took place in September 2007 with 56/60 participants (93%) completing all study visits.

Overall the vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccine recipients. Titres of pre-existing Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037).

Breadth of elispot response

 

elispot responses

Implications from results and other HIV Vaccine Trials

Based on results from the RV172 trial as well as the IAVI 001 and HVTN 204 phase I/II trials investigating the same HIV vaccine candidates (TRIAD Trials) further evaluation was planned for a phase IIb efficacy trial (PAVE 100). Mbeya was involved to recruit 700 HIV negative, high risk volunteers and study preparations were advanced. However, the Adenovirus type 5 vector containing PAVE 100 concept was stopped after results from the phase IIb STEP Study and the South African Phambili Trial were announced in September 2007. The STEP study which used a recombinant non-replicating adenovirus serotype 5 vector Merck HIV candidate vaccine (MRK Ad5) was discontinued early, because the MRK Ad5 vaccine was ineffective both at preventing HIV infection and at reducing viral loads in study participants who became infected with HIV during the trial. Of concern, more HIV infections were seen in people who received the MRK Ad5 vaccine than in people who got the placebo. Additional post hoc analyses demonstrated a trend toward a higher rate of infection for male vaccinees with prior immunity to rAd5 from natural as well as for uncircumcised men (www.stepstudies.com).

RV172 Amendment

Following the STEP and Phambili trial results the RV172 Trial was amended for a 2 years long term HIV safety and immunogenicity 4-monthly follow-up period. The RV172 Amendment started in Mbeya in June 2009 and will be completed in April 2011.

Sponsor

U.S. Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Health (NIH).

Partners

The trial is lead by the Walter Reed Army Institute of Research (WRAIR) and the U.S. Military HIV Research Program (MHRP). The study site partners are the:

U.S. Army Medical Research Unit-Kenya and Kenya Medical Research Institute in Kericho, Kenya

Makerere University-Walter Reed Project in Kampala,Uganda,

NIMR-Mbeya Medical Research Center (MMRC) in Mbeya,Tanzania

The LMU Department of Infectious Diseases and Tropical Medicine participate in this trial providing study coordination and management of the laboratory and immunology services. Logistical support is provided through the Munich office within the NIMR-MMRC collaboration.

Publications

Kibuuka H, Kimutai R, Maboko L, Sawe F, Schunk MS, Kroidl A, Shaffer D, Eller LA, Kibaya R, Eller MA, Schindler KB, Schuetz A, Millard M, Kroll J, Dally L, Hoelscher M, Bailer R, Cox JH, Marovich M, Birx DL, Graham BS, Michael NL, de Souza MS, Robb ML. A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172). J Infect Dis. 2010 Feb 15; 201(4):600-7