Navigating complexity to achieve clinical trial success

ICON is conducting a global, phase 1/2a clinical trial for a small biotech company to evaluate potential treatment for Parkinson disease (PD). There are approximately one million people living with PD in the United States (U.S.), and approximately 60,000 Americans are diagnosed with PD each year. The motor symptoms of PD are caused primarily by loss of dopamine (DA)-producing neurons in the substantia nigra. 

The sponsor’s target was to enrol 19 adult patients across 10 sites in the U.S., with administration of IP completed via intracranial injection of autologous stem cells into the putamen. Surgical procedure of IP was performed at only four of the participating sites. ICON delivered services across Clinical Operations, Study Start-Up, Data Management, Programming, Safety, and Medical Monitoring functions.

Dose readiness and IP availability 

All participants were recruited from the pool of patients who previously participated in the sponsor’s trial ready cohort study, and who met all eligibility requirements for entry into the trial-ready cohort. Recruitment of participants was to proceed for dosing/enrolment based on the chronological order of participant entry into the screening cohort study, to minimise the amount of time elapsed between skin biopsy and IP administration. The IP (autologous dopaminergic neuron precursor cells) was manufactured by the sponsor from the initial skin biopsy in the trial-ready cohort. Given the sponsor’s limited resources and manufacturing capabilities, enrolment was managed strictly by the sponsor, who informed ICON and the sites of IP availability and order of enrolment. 

Complex IP administration 

Given the complex nature of IP administration, a full tutorial/model of the IP administration was performed during the Investigator Meeting. While many sites were not actually administering the IP themselves, understanding the process of administration was important to allow education to sites to aide in the informed consent process and assist in addressing subject questions related to IP administration and process.

To ensure consistency of IP administration technique and subject safety, the sponsor worked closely with a primary neurosurgeon to develop a full procedural manual for the IP administration procedure. The Sponsor in conjunction with the primary neurosurgeon (and author) of the surgical manual, completed training and a walk through “sham run” with any additional IP administrators. Training on the surgical manual and successful completion of the sham run resulted in training approval and thus approval to complete the IP administration procedures/administration. The training sign off was filed in the site’s Investigative Site File (ISF) as well as the documented approval for the procedure/training on the site’s Delegation of Authority Log (DOA). ICON CRAs cross checked the site’s DOA to ensure IP administrator was delegated to complete IP administration as well as confirming site training of the sham run is filed in the site ISF.

In order to ensure the site neurosurgeon had adequate information to prepare for administration (plotting injection points), ICON imaging (IMI) assisted with collating the screening/baseline MRIs. The screening sites completed the screening/baseline imaging and uploaded the images to ICON’s SQUARE portal which allowed the dosing site/neurosurgeon to access the images and prepare for the intracranial injection/administration.

Start-up delays 

There were several delays in site activation due to inter-site dependencies and approvals required for full activation. Given the nature of the study, some screening site local IRBs required the dosing site IRB approvals in order to receive their own local approval. Additionally, given the nature of the IP (autologous dopaminergic neuron precursor cells), many of the institutions/sites required several different board reviews (including stem cell board review), which had to be incorporated into the overall start-up timelines.

Clear communication 

Transparent and open communication was essential to support sites and subjects in understanding clear timelines for IP availability and the likely order for enrolment. Site staff were asked to continue open communication with subjects ensuring the subjects felt supported and aware of the timelines for dosing (sometimes greater than one year after their initial entry into the screening cohort study). Active engagement with subjects was also encouraged to mitigate drop-out/lost to follow-up potential. 

Early detailed start-up engagement 

Following site selection, the site activation lead engaged early with sites, inclusive of a start-up phone call with ICON/Sponsor to ensure transparency and understanding of site requirements for approval. This differed from standard strategy, whereby a start-up email with more generic questions regarding timelines may be asked. Instead, the ICON team informed sites about our experience with “wheel and spoke” model and the requirements that may be needed by their local IRBs, prompting internal investigation and confirmation to ensure a clear understanding of requirements as well as more accurate start-up timelines. 

Unique recruitment approach 

A distinctive recruitment strategy was implemented by sourcing patients from a previously conducted cohort study with the same client, leveraging established relationships and prior engagement to streamline enrolment.

Despite the complexity and initial delays with study start-up, the team remained focused on the study and is planning to complete recruitment two weeks ahead of time. 

Looking ahead 

Our solution-oriented approach and commitment to collaboration have helped foster a strong, trusted relationship with the sponsor. The sponsor selected ICON to work on a new trial-ready natural history cohort study of Parkinson disease with the intent to dose an additional 120 subjects in a future trial. 

Contact us to discover how ICON’s trusted partnerships and deep expertise can accelerate your clinical trial delivery.