START Newsletter The Strategic Timing of AntiRetroviral Treatment – An INSIGHT Trial

February 2011

International Network for Strategic Initiatives in Global HIV Trials

SDMC: START@insight-trials.org

London ICC: START@ctu.mrc.ac.uk Washington ICC: CPCRA@va.gov

Sydney ICC: START@nchecr.unsw.edu.au Copenhagen ICC: START@cphiv.dk

START

ONWARDS AND UPWARDS

The 1000th

patient was recruited on the 25th

of

December 2010 and as of the 31st

January 2011, 1076

patients have been recruited across the open sites.

Table 1 below shows the recruitment summary by

country (as of 31st

January 2011) and the number of

sites currently recruiting in each country.

Table 1: Recruitment Summary by Country (31-Jan-11)

Country No. of patients

recruited

No. of sites in

country

USA 168 25 sites

Germany 167 17 sites

Spain 74 5 sites

France 68 11 sites

UK 61 5 sites

Argentina 61 7 sites

Brazil 57 2 sites

Thailand 52 2 sites

Belgium 47 2 sites

South Africa 43 1 site

Peru 42 3 sites

Australia 41 6 sites

Poland 32 1 site

Greece 27 3 sites

Chile 24 1 site

Mali 23 1 site

Denmark 23 2 sites

Morocco 16 1 site

Switzerland 16 3 sites

Finland 14 1 site

Italy 11 1 site

Israel 9 1 site

Figure 1: Current START Countries

Recruitment figures vary widely within each country and we

would like to thank all sites for their hard work so far and to

stress how important it is to keep recruitment at the same or

improved level. We would also like to especially congratulate

the top ten recruiting sites for this study. Our thanks go to:

1. Desmond Tutu HIV Foundation, South Africa 43 patients

2. Hospital Escola Sao Francisco de Assis, Brazil 40 patients

3.= Asociacion Civil IMpactat Salud y Educacion,

Peru

32 patients

3.= Chulalongkorn University Hospital, Thailand 32 patients

3.= Wojewodzki Szpial Zakazny, Poland 32 patients

6. Johann Wolfgang Goethe University Hospital,

Germany

26 patients

7.= Fundacion Arriaran, Chile 25 patients

7.= Hopital Saint-Louis, France 25 patients

7.= Institute of Tropical Medicine, Belgium 25 patients

10. Klinik fuer Innere Medizin der Universitaet

Koeln, Germany

24 patients

The successful recruitment at pilot sites has resulted in DAIDS

giving the go-ahead for the definitive phase of START. The main

study aims to recruit 4000 patients across all sites and with

current recruitment projections the study is expected to be fully

recruited before the end of 2012.

START EXPANSION PLANS

A further 137 sites have recently been approved for

participation in START, bringing the total number of START sites

to 238. Most new sites are located in countries already

participating in START, but some sites are in countries that are

new to this study including Austria, Czech Republic, Estonia,

Luxembourg, Norway, Portugal, Sweden, Uganda, Nigeria,

Ireland, India, Malaysia, Singapore, Mexico and Puerto Rico. An

overview of all countries with sites participating in START is

given in Figure 1, Current START Countries.

START Newsletter The Strategic Timing of AntiRetroviral Treatment – An INSIGHT Trial

February 2011

International Network for Strategic Initiatives in Global HIV Trials

SDMC: START@insight-trials.org

London ICC: START@ctu.mrc.ac.uk Washington ICC: CPCRA@va.gov

Sydney ICC: START@nchecr.unsw.edu.au Copenhagen ICC: START@cphiv.dk

START

CENTRAL DRUG REPOSITORY (CDR)

The INSIGHT network provides free study drugs for

patients enrolled into START, however, only

antiretrovirals that are approved and available within

a country can be obtained via the CDR.

All initial regimens should be prescribed according to

the document titled Antiretroviral Components

Required for Initial Regimen in START which is

available on the INSIGHT website and can be accessed

as follows:

Member log in -> HIV studies -> START -> Protocol

Materials -> Drug Management

The CDR is updated on a yearly basis following the

process outlined below:

1. Updating of the Clinical Trial Agreements (CTAs)

between Pharma and the Sponsor; this is

currently ongoing for the definitive phase.

2. Approval and printing of START drug labels; the

labels have recently been approved in all START

countries and are currently being printed.

3. Shipment of drugs to the repositories, ready for

order and shipment to sites.

Table 2 summarizes projected dates when drugs will

be available.

Table 2: Projected Drug Availability at Sites

Date New Site New Country* Drug

May 2011 No No New Drug(s)

May 2011 Yes No All Drugs

July 2011 Yes Yes All Drugs

* These countries did not participate in the pilot phase of START.

Please do not hesitate to contact your SCC or ICC if

you have any questions with regard to drug

availability. We are happy to help.

SUBSTUDIES OF START

START provides an excellent opportunity to gain more

detailed information about the impact of HIV and ART

on other body systems. Hence, a number of substudies

have been developed, including:

- The Arterial Elasticity (AE) Substudy

- The Pulmonary Substudy

- The Bone Mineral Density (BMD) Substudy

- The Neurology Substudy

- The Genomics Substudy

- The Informed Consent Substudy

Details about the different substudies can be found on

the INSIGHT website as follows:

Member log in -> HIV studies -> START -> Substudies

SUBSTUDY ENROLMENT

While most sites have managed to co-enroll the majority of

their patients into the Genomics Substudy, enrolment into the

Arterial Elasticity, Pulmonary and Neurology Substudies has

proven more difficult than anticipated. The substudies will all

provide important data on the START participants and we

would encourage all sites to continue with their efforts to co-

enroll as many participants as possible.

Some sites have done exceedingly well and after substudy

opening have managed to co-enroll 100% of their patients in

one or more of these substudies. These sites are as follows:

- Hospital Rawson, Argentina

- St. Vincent’s Hospital, Australia

- Centre Hospitalier Universitaire St. Pierre, Belgium

- Asklepios Klini St. Georg, Germany

- Gemeinschaftspraxis Jessen-Jessen- Stein, Germany

- Infectious Diseases and Pneumology Klinikum Dortmund,

Germany

- Universitaetsklinikum Erlangen, Germany

- Hospital Nacional Guillermo Almenara Irigoyen, Peru

- Universitatsklinik fur Infektologie, Switzerland

- Bronx-Lebanon Hospital Centre CRS, USA

- Henry Ford Hospital CRS, USA

- Minneapolis Medical Research Foundation, USA

- Naval Medical Centre San Diego, USA

- Temple University, USA

- Virginia Commonwealth University Medical, USA

Congratulations to all of these sites for their great efforts!

UPCOMING MEETINGS

NEXT INSIGHT INVESTIGATOR MEETING

An INSIGHT investigator meeting is scheduled in conjunction

with CROI for Sunday, 27 February 2011, 13:00-15:30 at the

Omni Parker House Hotel in Boston, Massachusetts, USA. A

buffet lunch for INSIGHT Investigators will be served prior to

the meeting at 12:00 noon at the hotel. If you are attending

CROI and are able to attend this meeting, please register on the

INSIGHT webpage as follows:

Member log in -> INSIGHT Meetings -> Upcoming Meetings ->

Registration

We are looking forward to seeing you there!

Data and Safety Monitoring Board (DSMB) Meeting

The next DSMB meeting is scheduled for April 2011. This will be

a full review.