Hundreds of millions of people around the world suffer from respiratory diseases—asthma, cystic fibrosis (CF), and bronchiectasis being among the most prevalent conditions. CF affects 1 in every 3600 children born in Canada, making it the most common fatal genetic disease in our country. There is currently no cure for CF, but there exist treatment options that have been shown to improve the symptoms and quality of life of people living with this debilitating condition.
Inhaled mannitol is a relatively new medication that helps facilitate mucociliary clearance in CF patients. After this drug passed through its initial clinical trial phase, an Australian biotechnology company and manufacturer of inhaled mannitol selected ethica CRO to conduct the Phase II and III clinical trial portions of their research programs to assess the safety and efficacy of inhaled mannitol for the treatment of CF and bronchiectasis.
Our clinical management personnel oversaw site management, recruitment, and monitoring, as well as eCRF data query resolutions for over 50 sites located across North America. After successfully navigating some major technical and regulatory challenges, ethica CRO proceeded to effectively design and manage the Phase II and Phase III trials that later led to the drug’s approval for the treatment of CF in 12 countries including, most recently, the United States.
About the Client
Our client was an Australian biotechnology company specialized in research and drug development for the treatment of cystic fibrosis, pulmonary fibrosis, and liver disease.
During the development of this research program, ethica CRO faced a number of technical and regulatory obstacles.
Firstly, research participants were required to undergo repeated spirometry testing to assess lung capacity at each study visit. In order to obtain viable data, however, testing frequency had to be uniform across all sites. This posed a great problem to the more physically restricted trial participants and especially those pediatric patients with significantly weakened lung capacity and physical strength. Some children were therefore incapable of undergoing spirometry testing at the same frequency as their older counterparts, yielding inconsistent data across sites.
Our second challenge was regulatory. While inhaled mannitol was listed as a natural health product by the Canadian National Health Products Regulations, its indication was considered a serious medical condition and therefore the drug had to be authorized by the Therapeutic Products Directorate. This meant that the research program for inhaled mannitol was required to go through a unique and robust regulatory review process under two separate Canadian health authorities, thus increasing our workload and delaying our timeline for regulatory review and approval.
For adult CF research participants, we developed a systematic approach to spirometry testing by employing pass-fail parameters evaluating the quality of spirometry measures and indicating if and when measures should be saved or re-assessed. We also modified the spirometry testing process to provide more flexibility to those pediatric research participants who were not physically capable of undergoing repeated spirometry testing. This new approach allowed for consistent spirometry testing frequency across all sites and led to more viable data.
As inhaled mannitol was considered a natural health product in Canada, we filed and conducted our studies under the Natural Health Products directorate while also answering to the therapeutic directorate. Success in this respect required a great deal of organization and cooperation between the study Sponsor and our clinical management team.
ethica successfully managed 3 clinical trials that led to the FDA’s approval of inhaled mannitol for the treatment of CF. The first clinical trial was a dose-response Phase II study to assess the effects of inhaled mannitol in pediatric CF patients across 12 Canadian sites, half of which were managed by ethica CRO. The second, a Phase III RCT, investigated the long-term effects of inhaled mannitol in pediatric and adult CF patients. The final study was a Phase III RCT in adult patients with bronchiectasis. In the last two studies, we managed 31 and 18 sites across North America, respectively.
Importantly, the client was so pleased with the quality and performance of ethica CRO’s clinical team that they further engaged our services in order to perform the rescue of a concurrent study being managed by a major US-based multinational CRO.
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