Case Studies

Client:

A US-based global pharma company with a novel cannabinoid drug for severe refractory epilepsies.

Project:

Evaluation of the safety and effectiveness of a novel cannabinoid drug in the treatment of children and adolescents with Dravet and Lennox-Gastaut syndromes.

Study Design:

The first trial was a dose-ranging pharmacokinetic study, published in 2018 and the second trial a placebo-controlled RCT of the drug in individuals with Dravet syndrome, published in 2017. The third study, undertaken in children and adults with Lennox-Gastaut syndrome, was published in 2018.

Services:

We were engaged to provide clinical leadership for the drug development programme and patient recruitment at the Alder Hey CRF as part of an international multicentre study. Alder Hey CRF was the highest recruiting centre internationally to all studies. Specialist expertise in the management of these patients and experience in complex study delivery was needed to conduct these clinical trials. As part of the New Drug Application process, the Alder Hey Lead Investigator was requested by the pharmaceutical company to present the medical aspects of Lennox-Gastaut syndrome to the 40-member committee of the EMA in February 2017. Approval was subsequently granted by both the FDA and the EMA.

Outcomes:

The NIHR Alder Hey CRF provided the clinical leadership, early phase trials expertise, recruitment to time and target and the high-quality environment to lead on the pivotal trials which have led to the first licenced, high-quality and pharmaceutical-grade medical cannabinoid to be licensed for the treatment of Dravet and Lennox-Gastaut syndromes.

Client:

A US-based pharmaceutical company which aims to create transformative medicines for cystic fibrosis (CF) patients.

Project:

Study to evaluate the effects and safety of a new drug in cystic fibrosis, a genetic life-limiting disease.

Study Design:

Recruiting patients with 2 copies of the most common CF gene variant, DF508 del, this international study involves 158 patients, 5 at Alder Hey. Previous studies on patients with one copy of DF508 del have shown life-altering results. Patients are randomised to receive this new treatment or an existing treatment in a doubleblinded fashion, following a 4-week run-in period of the existing treatment.

Services:

At inception, we became a recognised centre in the CF Trust-funded cystic fibrosis trials accelerator platform (CTAP). We maintained relationships with the pharmaceutical company and demonstrated the services we have to offer at Alder Hey, ahead of site selection for this highly competitive study. This study involves the respiratory team, CRF nurses, research laboratory team, pharmacy and ophthalmology.

Challenges:

Due to these previous dramatic positive study results, it was anticipated that all eligible patients would want to participate, therefore recruitment was done by random selection. A fair and transparent standard operating procedure was created to ensure smooth patient recruitment that offered equal opportunity. All patients completing the 6 month study will have the opportunity to enter the open label phase, allowing these individuals to receive this, anticipated, life-altering medication ahead of commercial availability. The CRF supported careful management of the high number of visits required for this infection-susceptible groups to ensure protocol adherence, with reduced risk.

Outcomes:

The study remains open with all patients recruited. Alder Hey CRF provides a safe clinical space for the conduct of this study, with our dedicated trials coordinator ensuring the required on-site multi-disciplinary team are optimising time.

Client:

A specialist company focused on a potential disease modifying therapeutic intervention for DMD, a rare, progressive and life-limiting neuromuscular disease.

Project:

A phase 3 study to evaluate the efficacy of the study drugs compared with placebo on ambulation, endurance and muscle function.

Services:

As one of 85 sites across 11 countries, with a recruitment target of 222 patients, this study requires input from multiple specialities necessitating close collaboration and coordination between the CRF team and multiple departments on site including cardiology, surgery, histopathology, radiology, biochemistry/ haematology, neuromuscular physiotherapy, CIVAS and the research department.

Challenges:

This high intensity study requires significant commitment from patients over a three-year period, with weekly intravenous infusions, and also substantial internal coordinating activities across multiple disciplines. Other intensive and invasive procedures, e.g. muscle biopsies and port-a-cath insertions, were supported by the CRF dedicated play specialist. Narrow eligibility criteria and screening requirements for this trial lead to significant screening failure, and patient recruitment was often external to Alder Hey, which necessitated close collaboration with the referring teams including logistical arrangements and communications with sponsors. The open-label extension allowed weekly home infusions which, again, required close collaboration with sponsor, vendors and Trust services.

Outcomes:

Recruitment has been to target and time. We continue to maintain an excellent working relationship with the sponsor and all vendors in this ongoing study. Due to the excellent multidisciplinary teamwork led by the dedicated CRF team we have been able to overrecruit to this trial and have novel ideas to further increase recruitment capacity.

Client:

A UK and USA manufacturer of solid dosage forms of medicines.

Project:

Determining the optimal size of tablets for young children.

Study Design:

A feasibility study to determine the ability of children aged 4-8 years to swallow placebo tablets of 6, 8 and 10mm size. Assessment of swallowability using physical assessment and standardised data collection instruments. Recording of participant facial expression during administration and completion of a range of patient reported outcomes of dosage form acceptability. Collection of feasibility parameters to inform a future, definitive randomised controlled trial.

Services:

Development of the study protocol and submission of all required regulatory approvals including design of age-appropriate patient information materials. Set up and maintenance of Trial Master File. Screening and recruitment of all study participants with informed consent. Receipt of QP released product and appropriate storage within the dedicated CRF dispensary. Administration of all interventions and collection of all studyrelated data. Analysis of data and preparation of full report and manuscript.

Challenges:

This was a challenging study to recruit children as either inpatients or outpatients. The CRF team developed multiple strategies to achieve successful recruitment, including non-hospitalised children. The expert CRF team was able to support children during the interventional phase of the study to achieve excellent compliance without compromising the scientific quality of the outcome data.

Outcomes:

The study recruited the target number of participants. Sufficient data was collected to enable the design of a larger, definitive trial to test acceptability and swallowability of different sized tablets in children.