ECRIN IA WP4 Breakout session: structuring a European rare disesase clinical research network ECRIN Annual meeting may 2013 Warsaw

Transcription

1 ECRIN IA WP4 Breakout session: structuring a European rare disesase clinical research network ECRIN Annual meeting may 2013 Warsaw OrphanDev s experience in supporting Clinical Trials for rare diseases Yolande Adjibi, OrphanDev s Project Manager Joëlle Micallef, MD, PhD, OrphanDev s coordinator 1

2 OrphanDev, lessons learned from rare diseases clinical trials Clinical Trial in Charcot-Marie-Tooth 1A (CMT 1A) Clinical Trial in Rett Syndrome Clinical Trial in Progeria 2

3 OrphanDev, lessons learned from rare diseases clinical trials On one hand, researchers with promising pre clinical data on animal models But don t know how to concept clinical trials On the other hand, clinicians with accurate knowledge of the disease, but don t know how to concept and run clinical trials pharmacologists, used to clinical trial issues, parmacocinetik, pharmacodynamic, dose etc. And do know how to concept and run a clinical trials 3

4 OrphanDev, lessons learned from rare diseases clinical trials All the experts were reunited but important issues remain : Need for validated experimental plan, and high quality trials Need for a feasible study in true life 4

5 OrphanDev, lessons learned from rare diseases clinical trials Sponsor Clinical Trial Assistant Serrious and unpredicatble adverse events Other health professionals: lab technician, Psychologist, EEG,physiologist Usual quality and regulatory requirements for all clinical trials (CT) Associate investigators Surveillance Independent committee Management of biologic samples: Kits, centrifugation, preservation, freezing, postmailing Paraclinic exams : TDM, MRI, EMG, cardiovascular exams Nurses Pharmacist : Therapeutic units management Patients organization 5

6 OrphanDev, lessons learned from rare diseases clinical trials Are added to rare diseases specificities and constraints 6

7 OrphanDev, lessons learned from rare diseases clinical trials METHODOLOGICAL CONSTRAINTS Unknown or poorly documented aetiology lack of knowledge concerning the disease progression Heterogeneity of the studied population Diseases chronicity Choice of primary outcome with several clinical symptoms to evaluate available number of patients vs necessary number of subjects 7

8 OrphanDev, lessons learned from rare diseases clinical trials PATIENTS RECRUITMENT Limited number of patients Inclusion criteria: phenotype, genotype, heterogeneity, severity degree Exclusion criteria: comorbidities, associated treatments, biological abnormalities Geographical dispersion 8

9 Specificities of clinical trials in rare diseases +Logistic burden+++ +Financial burden+++ 9

10 10

11 Specificities of clinical trials in rare diseases We are in front of an algorithm of choices 11

12 OrphanDev, lessons learned from rare diseases clinical trials METHODOLOGICAL STRATEGY to cope with the available number of patients. Collecting the most data available on the disease: natural history studies, registries, littérature review etc Alternative experimental designs Reduce the necessary number of subjects Reduce the trial periode Cross over, factorial design or adaptative methods: group sequential methods, add on design, randomized withdrawal design, N of 1, Continual reassesment 3 stage designs combined phases (1-2, 2-3) 12

13 OrphanDev, lessons learned from rare diseases clinical trials METHODOLOGICAL STRATEGY to cope with the available number of patients. Choice of outcomes Continuous outcomes Surrogate endpoints: We have to be very careful! This strategy has to be anticipated at very early stage because of interim analyses, on-time data management, decisions to be made 13

14 OrphanDev, lessons learned from rare diseases clinical trials PATIENTS RECRUITMENT STRATEGY set up before the trial adapted to each case Database and Registries Expert centers Others care units (trajectory of patients in the healthcare system) Early involvement of patients organizations++++ Centralized Call Center - pre-screening process 14

15 OrphanDev s experience 2005: First CT on CMT 1A phase II randomised placebo-controlled multicenter CT Dr Joëlle MICALLEF (PI), Clinical Pharmacology Unit, Marseille Collaboration of researchers, clinicians, pharmacologist, patients organizations A public-private partnership An orphan designation 15

16 OrphanDev s experience The recruitment Multicenter study: 3 French centers Specific disposal to improve recruitment : a unique phone number in Marseille Involvement of the patients organizations 180 CMT 1A patients included in 28 months Highest number of patients recruited in a RD CT at this time 16

17 OrphanDev s experience 2010: First industrial promoted CT on CMT 1A (ongoing) SAS Pharnext, EudraCT N phase II randomised placebo-controlled multicenter CT Pr Shahram ATTARIAN (PI), reference center for neuromuscular disorders, Marseille The recruitment Multicenter study: 6 French centers Involvement of the patients organizations before the CT A unique phone number in Marseille 17

18 OrphanDev s experience The recruitment Role of the call center: Information for patients (single contact) pre-screening by a CRA and a physician travel and time saving for non eligibles patients time saving for investigators screen-failure 80 CMT 1A patients included in 6 French centers in 8 months Respect of the inclusion period 18

19 OrphanDev: supporting clinical trial for rare diseases 2009: creation of OrphanDev In the Clinical Pharmacology Unit of the Timone Hospital, Marseille (CIC- CPCET), in a team with more than 25 years experience in pharmacology and CT Coordinated by Dr Joëlle MICALLEF, MD, PHD in Pharmacology Regional network Supported by CeNGEPS (National center of health products trials management) 19

20 Specificities of clinical trials in rare diseases The need: Overcoming organizational and methodological difficulties to: optimize the design and management of RD CT speed up the access to innovative therapeutics OrphanDev, a solution for therapeutic evaluation in the field of rare diseases : A platform dedicated to the clinical DEVelopment of ORPHAN therapeutics : 20

21 OrphanDev: supporting clinical trial for rare diseases OrphanDev since 2011: National network Renewal of the CeNGEPS support 21

22 OrphanDev: part of a national research network for rare diseases Involved in the French Foundation for rare diseases Coordinate means for research in rare diseases Directed by Nicolas Levy Involved in F-CRIN French part of ECRIN Directed by Vincent DIEBOLT, coordinated by Olivier RASCOL To reinforce the French Clinical Research in Europe and worldwide Involved in ECRIN-IA European Clinical Research Infrastructure Network Integrating Activity Coordinated by Jacques DEMOTES To structure pan-european investigating networks, focused on rare diseases, medical devices and nutrition. 22

23 OrphanDev: part of a national network for clinical research in rare diseases 23

24 OrphanDev,our know how support in and for: REGULATORY DOSSIERS, PROTOCOL REDACTION, information and consent notice, necessary number of subjects, ethical issues, LOGISTICAL ISSUES, start-up, ORPHAN MEDICINE DESIGNATION, academic, EMA PROTOCOL ASSISTANCE, TAILORED SOLUTIONS, call for projects, synopsys redaction, design, outcomes 24

25 To conclude High standards required for clinical trials Need for professional dedicated infrastructures All the more true for rare diseases, due to: methodological and logistical difficulties existing public-private partnership model ORPHANDEV network dedicated to clinical trials for rare diseases aims to meet the specific needs of support and synergy expressed by clinicians and researchers, whether academic or industrial acts in partnership with existing structures 25

26 Thank you for your attention 26