Since 2002 CVBF has been involved in clinical trial execution in the field of paediatric and rare diseases acting as Promoter and Contract Research Organisation (CRO). CVBF is registered as a non-commercial Sponsor of clinical trials at the European Medicines Agency (EMA) and is self-certified as Contract Research Organisation at Italian Medicines Agency (AIFA) since 2009.

Many activities are conducted in the context of EU funded projects and are focused on the development and application of innovative methodologies in clinical trials for small populations (e.g. rare diseases, paediatrics), as well as the management of interventional, non-interventional, health technology assessment, pharmacoeconomic studies, and disease registries.

With reference to the “Innovative models for clinical trials”, CVBF has also developed research activities aimed to develop and improve scientifically, clinically and logistically plausible alternatives to the classical designs for paediatric clinical trials. Such results have been included in training courses and peer-reviewed publications and have been applied in paediatric clinical trials.

Here is the list of the performed/ongoing studies:

Here is the list of the performed/ongoing studies:

CLINICAL TRIALS

The study intends to provide a prospective validation and clinical evaluation of safety and efficacy of a new posaconazole dosing regimen for children and adolescents with cystic fibrosis and Aspergillus infection.

Prospective multicentre randomised, placebo-controlled double-blind trial to verify the effects of the administration of probiotics on intestinal microflora in paediatric patients with Cystic Fibrosis.

A double blind, randomised, multicentre, active controlled, parallel-group, phase III trial to evaluate the efficacy, safety and pharmacokinetics of intravenous clonidine (hydrochloride) compared to midazolam for sedation in children from birth to less than 18 years of age. The study is aimed at comparing a new paediatric formulation of clonidine with midazolam. It is ongoing and involves 5 EU countries.

Multi-centre, oral single dose experimental and modelling study to evaluate the pharmacokinetics of deferiprone in patients aged from 1 month to less than 6 years of age affected by transfusion-dependent haemoglobinopathies. The study was concluded on February 2014, providing scientific evidence that the dosage of deferiprone used in adults can provide sufficient exposure to ensure efficacy also in small children and allowing children aged under 6 years of age to start to be recruited in DEEP-2 Safety/Efficacy Study. The study has enrolled a total of 23 patients, of which 18 were considered as evaluable.

Multicentre, randomised, open label, non-inferiority active-controlled trial to evaluate the efficacy and safety of deferiprone compared to deferasirox in paediatric patients aged from 1 month to less than 18 years affected by transfusion-dependent haemoglobinopathies. The study is aimed at comparing for the first time the efficacy and safety of deferiprone (DFP) vs deferasirox (DFX) in paediatric patients affected by hereditary haemoglobinopaties requiring chronic transfusions and chelation. The trial is ongoing and involves 344 paediatric patients starting from 1 month of age in EU and non-EU recruiting sites.

 Innovative Devices for the prevention of recurrent VAginitis

Randomized, double-blind, double-dummy, active controlled, multicentre, non-inferiority phase III study to compare the pharmacokinetic, efficacy and safety of gabapentin liquid formulation to tramadol in children from 3 months to less than 18 years of age experiencing moderate to severe chronic neuropathic or mixed. The protocol involves the enrolment of 94 patients to test the efficacy and safety of gabapentin monotherapy in the treatment of chronic pain with a neuropathic component.

Randomized, double-blind, placebo controlled, multi-centre, superiority phase II study to evaluate the safety, pharmacokinetic, efficacy of gabapentin liquid formulation as add-on to morphine in children from 3 months to less than 18 years of age experiencing severe chronic neuropathic or mixed pain. 66 patients will be enrolled to test the efficacy and safety of gabapentin in combination with morphine in the treatment of severe chronic pain with a neuropathic component.

Prospective, monocentric, post-CE mark study to assess efficacy and safety of Hymovis® SPORT (32 mg/4 ml) intra-articular injection in in the management of knee pain and function in active patient affected by knee osteoarthritis due to overuse.

Evaluation of nutritional suitability and tolerability of a Human Milk Oligosaccharide (HMO) Mix Infant Formula for term infants.

Observational study based on the collection of at least 1000 cases of juvenile idiopathic arthritis (JIA) and aimed to review the International League Against Rheumatism (ILAR) Classification criteria for JIA.

The primary clinical objective of this study is to establish the Optimal Biologic Dose (OBD) of losartan in 30 children aged 8-17 years with OI. Moreover, it aims to determine the changes in proxy efficacy outcomes of bone (mass, architecture and strength) and muscle (strength), and determine changes in quality of life using a validated disease-specific tool.

Efficacy, pharmacokinetics and safety of Meropenem in subjects below 90 days of age (inclusive) with clinical or confirmed late-onset sepsis: a European multicentre randomised phase III trial. The study ended in December 2014 with the enrolment of 272 patients.

Pharmacokinetics and safety of meropenem in infants below 90 days of age (inclusive) with probable and confirmed meningitis: a European multicenter phase I-II trial. The study ended in December 2014 with the enrolment of 51 patients.

Multi-centre randomised open label phase IIb study to compare the efficacy, safety and pharmacokinetics (PK) of an optimised dosing to a standard dosing regimen of vancomycin in neonates and infants aged less than 90 days with late onset bacterial sepsis known or suspected to be caused by Gram-positive microorganisms. The study is expected to start on 1st June 2016 and to enrol 300 patients.

Multi-centre randomized clinical trial to compare the safety and efficacy of Deferasirox and Deferiprone administrated in sequential mode versus Deferasirox or Deferiprone in monotherapy in patients affected by Thalassemia Major.

A Phase 2/3 multicentre, open-label, randomised study evaluating safety and antiviral effect of elvitegravir (EVG) administered with darunavir/ritonavir (DRV/r) compared to current standard antiretroviral therapy in HIV-1 infected, virologically suppressed paediatric participants . The study is expected to enroll 300 HIV-1 infected children aged 6 to < 18 years from Western and Eastern Europe, South Africa, Thailand, Uganda and Latin America.

A randomised trial of dolutegravir (DTG)-based antiretroviral therapy vs. standard of care (SOC) in children with HIV infection starting firstline or switching to second-line ART. The study is expected to enroll 700 HIV-1 infected children trial to evaluate the efficacy and safety of once daily DTG-based ART.

A prospective, double blind, randomised, 24 month study to assess the effect of prebiotic Galacto-oligosaccharide/polydextrose (GOS/PDX) supplemented formula compared with standard formula in preventing and modifying the history of allergy and acute infections in infants at risk of atopy.

A 36-months multi-centre randomized interventional pragmatic trial to evaluate the effectiveness and safety of glatiramer-acetate (GA) compared to interferon-beta (IFN-beta) in paediatric patients affected by multiple sclerosis.

A randomized phase II/III trial of doxycycline (versus standard supportive therapy) aimed at establishing whether the addition of the antibiotic doxycycline to anti-plasma cell therapy can reduce early mortality in newly-diagnosed patients with cardiac AL amyloidosis.

A phase 2/3 multicentre, open-label, randomised study aimed at evaluating the safety and antiviral effect of once daily integrase inhibitor administered with darunavir/ritonavir (DRV/r) compared to the current standard antiretroviral therapy in HIV-1 infected, virologically suppressed paediatric participants.

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A multi-centre, randomised, single blind phase II trial to evaluate the pharmacokinetics and PKPD relationship of trazodone after single and repeated oral doses in children from 2 to ≤17 years of age, suffering from insomnia, with autism, intellectual disability or attention deficit hyperactivity disorder (ADHD).

Non-interventional studies

Long-term observational safety study of deferiprone use in paediatric patients. The study evaluates the nature and incidence of adverse effects of deferiprone (DFP) in children and adolescents with beta-thalassaemia major. Patients treated with deferiprone are followed up throughout their treatment, from its start up to conclusion in October 2015.

Study on Quality of Life, treatment satisfaction and economic burden of disease in patients with b-thalassemia major undergoing iron chelation treatment/Qualità della vita, soddisfazione del paziente e costi della malattia in pazienti affetti da β-talassemia major sottoposti a trattamento di chelazione del ferro (HTA-Thal, “Inter-regional Network for Thalassaemia: HTA for the diagnostic and therapeutic intervention for iron overload”). The study consisted of 24-month observation period with different levels of information recorded in the first and second year of observation. The aim of this study was to assess the economic impact of thalassaemia and the burden of disease in terms of health-related quality of life (HRQoL) in a cohort of 272 adolescent (>12 yrs) and adult thalassaemic patients. The study was also aimed at investigating compliance, quality of life, patients’ satisfaction and costs associated with the different iron chelating treatments, in the perspective of the Italian Health National Care System and the society.

Quality evaluation of the informative booklets for patients involved in the DEEP-2 trial (QuBo). The aim of the study is to investigate the quality of the informative material addressed to paediatric patients involved in the DEEP-2 study, in order to evaluate the level of comprehension and the likeability of the informative documents for paediatric patients. Particularly, QuBo foresees the administration of an age-tailored structured questionnaire to directly collect the children’s and adolescents’ opinion on the DEEP-2 informative material.

OTHER STUDIES

OTHER STUDIES

Population pharmacokinetics meta-analysis based on all available published studies and data collected during clinical practice to determine the optimised dosage regimen of vancomycin to be used in children less than 3 months of age.

Model-based bridging of clinical data for children from 3 months to < 3 years to simulate PK/PD, clinical efficacy and safety data of gabapentin in children from 3 years to less than 18 years of age in chronic pain.

A systematic review analysing the methods of treatment of sepsis and the factors causing antibiotic resistance in neonatal population is ongoing. The review is focused on the situation in five major European countries and results will been soon provided to the customer (Chiesi Farmaceutici SpA).

PHARMACOECONOMIC ANALYSES

PHARMACOECONOMIC ANALYSES

A pharmacoeconomic and HTA evaluation on the use of deferiprone formulation in paediatrics aimed to guide the inclusion of the drug in the current Protocol and Guidelines.

A market analysis aimed to determine the share of paediatric patients that could be treated with clonidine for sedation including possible competitors and potential profitability.

A HTA report including a cost/benefit evaluation aimed to guide the implementation of clinical recommendations for the use of gabapentin as monotherapy and/or add-on therapy.