Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare indication with a very low global prevalence of 1 in 2 million people. Due to the low prevalence of this indication, the patient population eligible for this trial from a pool of approximately 940 adult FOP patients was slightly over 50%, and in an environment with high study competition this limited the existing patient population.

As a result of the rare nature of the indication, each patient journey had to be considered unique and required individual patient support for trial information, travelling to site, overnight stays as well as on-site comforts during waiting room time to ensure patient recruitment and retention targets were met. Many of the selected sites were clinical trial naive and required very close support from the study set-up throughout study conduct. This particular patient population also need to consider the burden and rigor of travel potentially worsening their prognosis and injection sites can cause more lesions (turning to bone formation). Most patients are wheel chair bound and unable to flexibly move and some may require air ambulance transport or specialist ambulance service as they may be in a constant supine position. Each site will need to consider the housekeeping of their site for patient comfort to ensure trial access and retention is acknowledged and well set-up from the beginning of the study.

The recruitment study logistics were very complex as many sites had cross border patients, including numerous participants that were flying from one country to another to join the trial. For example, patients flew from Greece and Malta to UK and from Jordan to the US with a medical visa for 1 year.

Some additional imaging related operational challenges were encountered as patient’s skeletal structure could limit imaging (CT/PET-CT) due to inability to fit into the scanner requiring specific imaging protocols to be in place. Also, some of the imaging centers were separate from the main site location adding further complexity.

Engaging with well-known key opinion leaders in the indication and conducting very early site outreach to gain site feedback on protocol, capabilities, patient pool and referral support mitigated the risk of not selecting the right site profile. Sites were supported though start up with a single point of contact to facilitate communications, ensuring both a clear process to exchange of information and convey responsibilities to ensure site staff engagement, whilst the CRAs supported the sites with cross departmental set up and careful planning.

Implementing a site and patient support solution though patient recruitment services:

ICON provided a tailored solution using FIRECREST with a pre-screening tool plus a patient targeted video for adolescent patients. Also provided were a patient website as well as site and patient recruitment aids, information leaflets to facilitate enrollment, as well as age appropriate booklets to explain the patients’ journey.

Close collaboration was established with Patient Advocacy Groups in an outreach programme to proactively communicate to groups and organisations. ICON provided travel concierge services to facilitate travel to/from site for patient and caregiver including overnight accommodation as well as cross-border travel. Home visits were implemented to reduce travel burdens, risk and inconvenience
on patients and their families. To support cross border patient recruitment, one of the sites in Italy acted like a European hub for European FOP patients who came from other countries to join the study and air ambulances were organised for some patients to get to site due to their unique fused position (based on bone formations). The FOP community are very well informed and connected. Sponsor presence on social media and with PAG’s regarding their contribution to FOP research was strongly recommended given that if patients positive experience was shared on social media this would have a very positive effect on recruitment.

Providing Firecrest training for clinical trial naïve sites:

Firecrest training covered an overview of Clinical Research/GCP, site identification processes, startup documentation, successful recruitment and patient engagement. Experienced rare disease CRA’s were assigned to support sites through entire study duration. Sites were provided with additional start-up support using a single point of contact per site if possible, as well as ongoing PM/CTM support and medical monitoring monthly dosing calls with sites. Developing a specific imaging charter devised between the sponsor and ICON imaging services was instrumental in allowing many updates to the charter as the imaging review was evolving, due to ultra-rare indication and the low experience of the readers in this indication.

Patient recruitment started slowly but once first couple of patients entered study and the patients were vocal on social media, recruitment escalated and completed earlier than expected in12 months.

The study recruited more patients than initially planned in a shorter timeframe. Last patient randomised was planned on April 30, 2019 and recruitment finalised on the March 4, 2019.

The overall study results were very encouraging and FDA has approved Phase 3 which is starting at present.