My Experience in the My Experience in the PROTECT-1 StudyPROTECT-1 Study

MUDr. MUDr. CompeCompeľ Vladimírľ Vladimír

Dear colleagues, It is a great honour for me to participate in today´s proceedings of the conference.I appreciate your invitation a lot.It is a pleasure for me to get a chance to meet the ChemoCentryx staff who support the development of a high quality and high efficiency medicament treating Crohn disease. 

Study Center Personnel

Principal Investigator: MUDr. V. Compeľ VladimírSub-Investigator: MUDr.Procházka Bohumil Study Coordinator: PharmDr. Lobotková Miriam

Study Location

Private Gastroenterology Centre Senovazne namesti 1616

370 01 České Budějovice Czech Republic

Study Statistics

• Study site was initiated on 20 April 2007• Eleven patients have been screened to date• The first patient was randomized on 11 May

2007• Six patients have been enrolled so far into

the Induction Period• Three patients have been enrolled into the

Maintenance Period • Five patients have failed screening because

of low CRP

Enrollment Rate Compared to Other Study

Sites0.97

0.28

0

0.25

0.5

0.75

1

Compel All Sites

Month

ly R

ecr

uit

ment

Rate

I have been asked to present our experiences acquired within the process of treating patients suffering from

Crohn disease in the beginning of our studies and to give away our secrets.

We all know well the work is demanding, the choosing of patients complicated

inclusion and exclusion criteria limiting

I myself am convinced that we do not have any secrets but you may be interested in our system of working with

the patient.

My Experience in the PROTECT-1 My Experience in the PROTECT-1 StudyStudy

In each patient we usually start with the standard initial interview, besides, - each patient gets informed about the disease and treatment - each patient gets informed about the follow up visits - each patient gets informed about the prognosis - each patient is provided with printed information materials. In the process of endoscopy and ultrasound examination the patient is being informed about the scope of the disease both verbally and visually (he or she is able to follow the process of examination accompanied by our commentary). I am convinced that the information process as described above presents an integral component of services provided generally.

My Experience in the PROTECT-1 My Experience in the PROTECT-1 StudyStudy

The following slides should stress the fact that the The following slides should stress the fact that the ultrasound ultrasound examination of Crohn disease examination of Crohn disease of of patients should be patients should be carried out carried out under a friendly and amicable atmosphere, under a friendly and amicable atmosphere, that a that a patient – doctor relationshippatient – doctor relationship based on mutual based on mutual trust and trust and co-operation should be established. co-operation should be established.

The patient will appreciate thorough information The patient will appreciate thorough information concerning concerning

the exact place of the exact place of action of the medicationaction of the medication administered within the study.administered within the study.

My Experience in the PROTECT-1 My Experience in the PROTECT-1 StudyStudy

It is obvious that Crohn disease affects all layers of the It is obvious that Crohn disease affects all layers of the intestine wall. intestine wall.

In accordance with the scope of affliction of the In accordance with the scope of affliction of the individual layers the disease can be monitored, asindividual layers the disease can be monitored, as … ….. .. an an acuteacute, subacute , subacute or chronic conditionor chronic conditionThe ultrasound examination can detect and monitor The ultrasound examination can detect and monitor various various complicationscomplications or responses within the or responses within the surrounding areas – especially in messentersurrounding areas – especially in messenteryy, nodes, , nodes, abscesses, invagination, fistulaabscesses, invagination, fistulaee, stenoses, prestenotic , stenoses, prestenotic dilatations of the intestine etc.dilatations of the intestine etc.

Due to the fact that the patient is encouraged to follow Due to the fact that the patient is encouraged to follow the ultrasound monitor, he or she is interested inthe ultrasound monitor, he or she is interested in --  what his or her intestine what his or her intestine wall lookswall looks like, like, -- how how thickthick it is, it is, -- how it gets how it gets supplied with bloodsupplied with blood,, -- whether whether nodesnodes around the afflicted intestine detected around the afflicted intestine detected in the in the previous examination are visible etc…previous examination are visible etc…..

In this way In this way the patientthe patient gets gets fully engagedfully engaged into his or into his or her disease, during each visit the patient her disease, during each visit the patient can followcan follow the the development of the disorder, the results of treatment, development of the disorder, the results of treatment, regime mistakes, worsening of the conditionregime mistakes, worsening of the condition etc…. etc….

The same principles are applied during the initial The same principles are applied during the initial interview with the patient when we usuallyinterview with the patient when we usually(in compliance with the printed patient information (in compliance with the printed patient information materials provided by ChemoCentryx Inc.)materials provided by ChemoCentryx Inc.) -- stress the place of stress the place of effect of the new medicamenteffect of the new medicament -- in this case in this case = = the the submucossubmucosaa of the intestine wall of the intestine wall --  lymphocyteslymphocytes in the submucos in the submucosaa with their inf with their inflammatorylammatory activity activity and production mediators and production mediators of inflammationof inflammation --  lymphocytes with the described CCR9 lymphocytes with the described CCR9 receptorsreceptors which which are are blocked by the medicamentblocked by the medicament  Thus, we are able to achieve a better compliance with the Thus, we are able to achieve a better compliance with the

applied study medicament. applied study medicament.   

We have no other secrets. We have no other secrets.

The The next next slides will show the terminal ileum slides will show the terminal ileum afflicted by Crohn disease in a afflicted by Crohn disease in a female patient female patient

participating in participating in the studythe study, including the development of , including the development of

changes changes when treated by CCwhen treated by CCXX282-B 282-B

(the original medication stayed unchanged).(the original medication stayed unchanged).

Normal wall of caecumNormal wall of caecumThe wall thickeness here The wall thickeness here

amounts to 1.2mmamounts to 1.2mm

The afflicted The afflicted terminal ileum terminal ileum

(the wall 4-8mm(the wall 4-8mm

Somewhere here Somewhere here there will be there will be Bauh.valve Bauh.valve

I explain to my patients I explain to my patients - here your Crohn disease is well visible- here your Crohn disease is well visible - here your immunity cells are concentrated - here your immunity cells are concentrated („disoriented („disoriented lymfocytes“) which produce pro-inflammatory lymfocytes“) which produce pro-inflammatory mediators mediators

Chronic appearance of the submucosa

Subacute appearance of Subacute appearance of the submucosathe submucosa

(well blood-supplied (well blood-supplied submucosa …i.e.an intensive submucosa …i.e.an intensive

infiltration by immunity cells) infiltration by immunity cells)

the length of the affected terminal ileum section the length of the affected terminal ileum section (here approximately 7cm = 3,6 plus 3,3cm) (here approximately 7cm = 3,6 plus 3,3cm)

- the - the thicknessthickness of the wall amounts to 8 mm of the wall amounts to 8 mm- the submucosa has the submucosa has oedematousoedematous character character - doppler suggests a - doppler suggests a high blood supplyhigh blood supply to the area to the area

And besides, an inflammatory – hyperechogeneous messentery can be And besides, an inflammatory – hyperechogeneous messentery can be observedobserved

Before CCX282-B therapy July 24, 2007

- the - the thicknessthickness of the terminal ileum has of the terminal ileum has decreaseddecreased- the - the blood supplyblood supply of the wall has of the wall has decreaseddecreased- the submucosa - the submucosa swellingswelling has has decreaseddecreased .. i.e.the .. i.e.the infiltrationinfiltration of of the terminal ileum by further immunity cells has the terminal ileum by further immunity cells has decseaseddecseased

During CCX282-B therapy 17.sep.2007

the thickness of the termilnal ileum wall in its the thickness of the termilnal ileum wall in its individual individual segmentssegments does not exceed 0,9 ... 2,4 … 2,8mm. does not exceed 0,9 ... 2,4 … 2,8mm.

It is obvious that when the patient has the chance to see these changes he or she is pleased both by the improved condition and the medication.

As a result, his or her compliance with the new drug has increased.

During CCX282-B therapy 17.sep.2007

… … Thanks for your atention Thanks for your atention ……