DEEP-3 study

Palermo, 06 ottobre 2014

Palermo  15  Dicembre  2012  

Do#.  ssa  Angela  Vitrano  

U.O.C   “ Ematologia  e    Mala7e  Rare  del  Sangue  e  degli  Organi  Ematopoie=ci  “   A.O.   “ Riuni=  Villa  Sofia  Cervello ” -­‐  Palermo  

WHAT  IS  DEEP-­‐3?   DEEP-3

is an observational safety study to evaluate the nature and incidence of adverse effects of deferiprone treatment in patients with beta-thalassaemia major aged from 1 month to less than 18 years.

CONFIDENTIAL

  Product: DEFERIPRONE Protocol No.: DEEP-3 Sponsor: Universitätsklinikum Erlangen

Maximiliansplatz 91054 Erlangen, Germany

Trial Coordinating Investigator: Dr. Maria Caterina Putti

Azienda Ospedaliera di Padova Via Giustiniani, 35128 Padova, Italy

Funder: European Commission

(FP7 Framework Research Program “HEALTH- 2010.4.2-1: Off-patent medicines for children”)

RECRUITMENT  SITES  AND  PRINCIPAL   INVESTIGATORS  

Town  

Cairo   Athena   Tirane   Nicosia   Tunis     Napoli     Palermo  

Country  

Egypt   Greece   Albania   Cyprus   Tunisia   Italy   Italy  

Ins=tu=on  /  address  

Cairo  University  Faculty  of  Medicine   Al  Orman  Guiza,  Giza  12613   NaMonal  And  Kapodistrian  University  Of  Athens   CHRISTOU  LADA,  6  -­‐  10561  Athena   Qendra  Spitalore  Universitare  "Nene  Tereza"  Tirane   RR  Dribes  370,  Tirana   Cyprus  Ministry  of  Health,  Nicosia  Thalassaemia   Center,  Koritsas  Street,  6  1474  Nicosia   Centre  naMonal  de  Greffe  de  Moelle  Osseuse,  Rue   Jebel  Lakhdar,  Bab  Saadoun,  1006  Tunis   Azienda  Ospedaliera  di  Rilievo  Nazionale  "Antonio   Cardarelli",   Via  A.  Cardarelli,  9  -­‐  80131  Napoli   Azienda  ospedaliera  Ospedali  RiuniM  Villa  Sofia-­‐   Cervello,   Viale  Strasburgo  233  -­‐  90146  Palermo  

Principal   Inves=gator  

Prof.  Amal  El-­‐ Beshlawy   Prof.  Antonis   KaUamis   Dr.  Eleni  Nastas   Dr.  Soteroula   Christou   Prof.  Mohamed   Bejaoui   Dr.  Aldo  Filosa   Prof.  Aurelio   Maggio  

RECRUITMENT  SITES  AND  PRINCIPAL   INVESTIGATORS  

Town  

Padova   Bari   Palermo   Cosenza   LenMni  SR   Modena   Sassari   Cagliari   Firenze    

Country  

Italy   Italy   Italy   Italy   Italy   Italy   Italy   Italy   Italy  

Ins=tu=on  /  address  

Azienda  Ospedaliera  di  Padova,   Via  GiusMniani,1  -­‐  35128  Padova   Azienda  Ospedaliero-­‐Universitaria,  Consorziale  Policlinico  di  Bari   Piazza  Giulio  Cesare  -­‐  70124  Bari   ARNAS  "CIVICO-­‐DI  CRISTINA-­‐BENFRATELLI"  P.O.  CIVICO-­‐PALERMO,   U.O.C.  Ematologia   Piazza  N.  LeoUa,  4  90100  Palermo   "  Presidio  Ospedaliero  Azienda  Ospedaliera  Cosenza   Stabil.  "Annunziata“,  Centro  di  Studi  della  Microcitemia  U.O.C.   EmatologiaVia  Felice  Migliori  –  87100  Cosenza   Ospedale  Civile  di  LenMni,  Centro  di  Thalassaemia,   Via  Ospedale  96016  LenMni   Policlinico  di  Modena,  Clinica  Pediatrica   Via  del  Pozzo,  71  41100  Modena   Azienda  Mista  Ospedaliera-­‐Universitaria  di  Sassari   Clinica  Pediatrica  Università  -­‐  ASL  1  D.H  per  Talassemia   Viale  S.  Pietro,  12  07100  Sassari   Ospedale  Regionale  per  le  Microcitemie-­‐ASL8  Cagliari   Via  Jenner  09121  Cagliari   Azienda  Ospedaliero-­‐Universitaria  Meyer   Viale  Pieraccini,  24  50139  Firenze  

Principal  Inves=gator  

Dr.  Maria  Caterina   Pub   Dr.  Giovanni  Carlo  Del   Vecchio   Dr.  Liana  Cuccia   Dr.  Mariagrazia   Bisconte   Dr.  Francesca   Commendatore   Dr.  Giovanni  Palazzi   Dr.  Carlo  Cosmi   Dr.ssa  Raffaella  Origa   Dr  Tommaso  Casini  

OBJECTIVE(S)   Primary

To investigate

serious adverse reactions

related to deferiprone treatment in children aged 1 month - 18 years diagnosed with beta-thalassaemia major.

Secondary

To investigate: •  

non-serious adverse reactions

related to deferiprone treatment in children aged 1 month - 18 years diagnosed with beta-thalassaemia major •  

risk factors for ADRs

related to deferiprone use

INVESTIGATIONAL  PLAN  

Ø  

Study Design/Schematic

This is a multi-centre, multi-national, observational cohort study. Patients will be identified and data collected both retrospectively and prospectively. Ø  

Study Duration

Observation period is defined from the start of deferiprone treatment up to conclusion or October 2015 whatever comes first. Ø  

Dosage, treatment regimen, route of administration

Any dose of deferiprone is acceptable. For prospective data collection only authorised dosage are acceptable. Ø  

study population

All patients with beta-thalassaemia major treated with deferiprone for iron overload and being aged 1 month to <18 years at the time of initiation of the therapy will be included in the study.

ELIGIBILITY  CRITERIA   Inclusion Criteria:

1.

  Patient has beta-thalassaemia major; 2. Patient has received deferiprone, either as monotherapy or in combination with deferoxamine (DFO); 3. Patient is aged 1 month to <18 years at the start of therapy with deferiprone; 4. If data are collected retrospectively a minimum set of data (as defined in next slide) must be available.

ELIGIBILITY  CRITERIA  

Minimum data set

A minimum data set to be available and recorded for data collection is defined as follows: 1. Demographic data 2. Exact dose and type of deferiprone treatment (including also name of the product, start and end date) 3. HIV and hepatitis C, B status 4. Spleen size: splenectomised, normal, splenomegaly (once/year) 5. Annual amount of transfused PRBC (blood units or cc PRBC /kg/year) 6. Complete blood cell count and biochemical profile (creatinine, glucose, AST, ALT,GGT, leukocytes (WBC), neutrophils, haemoglobin, platelets) at least 4 values/year 7. Ferritin levels at least once/year

ELIGIBILITY  CRITERIA   Exclusion Criteria

1.

  Previous therapy and medical records cannot be obtained from the clinicians (for the retrospective data collection). 2. A minimum set of data cannot be obtained 3. Patient has participated in an investigational study during the time of deferiprone therapy and no consent to use data has been obtained from the sponsor of the investigational study 4. Inability or unwillingness to sign consent form from parents/legal representatives and/or the patients. (for prospective data collection) 5. Patient has received deferiprone as off-label use (for prospective data collection)

STUDY  ASSESSMENTS    

Retrospective data

Data for patients which already commenced deferiprone treatment at the time the study commences will be collected retrospectively using intensive chart review. All medical and therapy records of these patients will be screened manually by trained researchers locally at each study site. A unique anonymised identifier will be given to each individual patient to protect patients’ confidentiality. If the patients continue taking deferiprone at the time the study commences data collection will be continued prospectively.

Prospective data

Prospective data will be collected by the treating clinician supported by research staff. Prospective data concern data from patients newly starting on deferiprone before October 2014 and data from patients which continue to take deferiprone. For each consequent visit of the patient, clinicians will be asked to report any adverse drug event (ADE) in patients under their care. Clinicians will be reminded to collect data at each routine visit.

DATA  TO  BE  COLLECTED  

Demographic

•   Patient identifier •   Date of birth •   Genotype •   Gender •   Ethnicity

Baseline data

•   Height and Weight before starting therapy •   Tanner stage, Spleen size, Body mass index before starting therapy •   Transfusion therapy (amount, frequency, annual blood cell consumption) •   Chelation therapy (age/year of initiation of therapy, type and dosage of previous therapy) •   HIV and Hepatitis C, B status

DATA  TO  BE  COLLECTED  

Ø  

Diagnosis

All chronic and acute diagnoses will be obtained and classified using ICD 10. The information to be collected comprise of the following •   Date of diagnosis, Diagnosis Text, and Diagnosis Code ICD 10 Ø  

Medication

All chronically used medications (taken for >1 month) prescribed along with deferiprone will be documented and classified using ATC terminology. Any dose alterations will also be documented. Medication chart are updated at each visit. .

DATA  TO  BE  COLLECTED  

Ø  

Laboratory test results Haematology

• Haemoglobin*, Haematocrit • Erythrocytes (RBC) • Erythroblasts • Leukocytes (WBC)* • Neutrophils* • Platelets*

Biochemistry

• Sodium, Potassium, Serum creatinine*, Alkaline phosphatase (AP) • Aspartate aminotransferase (AST, SGOT)* • Alanine aminotransferase (ALT, SGPT)* • Gamma-Glutamyl transpeptidase (GGT)* • Total bilirubin, Total protein, Albumin, Uric acid, Urea, Glucose*, Serum ferritin*

DATA  TO  BE  COLLECTED  

Ø  

Adverse Event Data

•   Type of ADR using MedDRA •   Start date (and time) of onset of reaction •   Stop date (and time) or duration of reaction •   Additional comments (e.g. clinical notes to explain the cause of ADR, consequences of ADR) •   Severity

Data Management

v   Data entry into the e-CRF

ARRUOLAMENTO  DEEP-­‐3

  Studio Retrospettivo Attivare Agreement Monitor dell’ AOR Villa Sofia-Cervello provvede alla raccolta dati presso il Centro arruolante Somma di 900,00 Euro per paziente erogata dall’AOR Villa Sofia-Cervello vs Centro arruolante

Thank you