Using biomarker clinical trial design to drive rare respiratory disease results

Simbec-Orion recently helped a biotech sponsor demonstrate the safety and tolerability of a new trial treatment for idiopathic pulmonary fibrosis (IPF). Devising an effective umbrella trial design adapted to the needs of IPF patients, we were able to deliver final CSR results ahead of time.

Our researchers devised and conducted the umbrella study design testing healthy volunteers to rare patient cohorts, investigating the lead molecule, direct target engagement and biomarker effects for IPF in a short space of time.

As a result, the sponsor has been able to report positive results on the safety and tolerability of the new treatment in IPF patients and source further investment into the compound’s development. 

View the full study details in our IPF trial case study report.

Umbrella clinical trial design

An umbrella clinical trial assesses the performance of a new test drug in patients who share the same disease, but with different molecular alternations or biomarkers. Patients are given treatment based on the specific biomarker that stratifies their condition, testing how well the drug works in different individuals. 

In this study, the umbrella trial design evaluated the treatment’s safety and tolerability across healthy volunteers to rare patient cohorts, using biomarkers to monitor the effects in different IPF patients. 

Biomarker clinical trial research

Biomarkers are used across clinical trials for a range of practical uses. From screening patients, monitoring responses to test drugs, classification into subgroups and correlating study results for future reference. 

During this IPF clinical trial, biomarkers were used to assess the pharmacokinetic and pharmacodynamic properties of the study drug. This allowed researchers to determine the treatment’s tolerability in healthy and rare patient groups, as well as identify potential adverse reactions and side effects.

Safety biomarkers were used progressively across participant groups to evaluate:

  • The pharmacokinetics (PK) and pharmacodynamics (PD) of the study drug when administered as a single dose to healthy male subjects
  • The safety and tolerability of multiple doses of the study drug in male and female patients of non-childbearing potential with IPF
  • The pharmacokinetics (PK) and pharmacodynamics (PD) of the study drug when administered in multiple doses to male and female patients of non-childbearing potential with IPF

As an integral part of the study design, biomarkers were key to the success of the clinical trial, allowing the sponsor to demonstrate the drug’s safety profile and dosage requirements. 

Challenges in IPF research

As a rare disease, IPF presents itself in around 13 to 20 people per 100,000 people worldwide. There has been a lack of clinical development in IPF treatment, with an unmet medical need to develop an effective treatment. 

One of the main challenges in rare disease research is that there are strict study inclusion and exclusion criteria regarding who can participate in the trial. This meant that patient recruitment would be difficult for this study. 

A number of IPF patients could not be enrolled in the study due to the severity of their condition. As well as having to meet study criteria, patients also had to produce a suitable forced expiratory volume (FEV) value in order to be considered for study participation.

Patients were admitted to the hospital sites on days 1, 7 and 14. Each patient was given the IPF study drug for dosing at home, which presented challenges in monitoring the administration of the drug since this relied heavily on participants. Ensuring that all participants were trained on correct and consistent inhaler use was critical to success. 


With therapeutic expertise in rare disease clinical trials, we are accustomed to adapting trial designs to unique challenges. For this IPF trial, we identified patient enrollment as a key challenge. 

To overcome this, additional sites were identified prior to the research taking place in order to expand the reach and encourage study inclusion. The site and IPF patient identification ran in parallel to the healthy volunteer study in order to facilitate rapid patient enrolment.

To oversee and manage the challenging patient enrollment process, a centralised Simbec-Orion project manager was appointed to streamline communication across several sites. Centralised set up and management of all cohorts ensured agile data management and resolution

The efficient, centralised set-up of the Simbec-Orion project and management teams stripped out much of the delay associated with the increased complexity, and disparate geography of teams, hierarchies, and processes at larger CROs 

Training was provided to participants by the CRA on correct inhaler usage in order to ensure consistent results and dosages throughout the trial in both healthy and patient group populations. 

Trial outcomes

Simbec-Orion was able to deliver results ahead of schedule, providing clinical data on the safety and tolerability of the test IPF treatment. This was achieved through risk identification and mitigation, putting the necessary measures in place to ensure the challenge of patient enrollment did not hinder the progress. 

The risk of slow recruitment was identified early on, and then addressed to deliver the final CSR ahead of time. The research was accelerated by an effective umbrella trial design, allowing the new drug development process to progress faster than through a typical clinical trial design.

The sponsor has been able to report positive results on the safety and tolerability in IPF patients. The sponsor is now in a position to source investment to develop the compound further, or to license the compound.

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