Evolution
Research type
Research Study
Full title
Safety and dose ranging study for OWL-EVO1 as a lung cancer eVOC probe
IRAS ID
288256
Contact name
Robert Rintoul
Contact email
Sponsor organisation
Owlstone Medical Ltd
Eudract number
2020-004433-20
Duration of Study in the UK
0 years, 7 months, 16 days
Research summary
Owlstone has recently pioneered the EVOC approach which enables active investigation of disease specific pathways by administering probe compounds to patients and measure its signal on breath. In the Evolution-study, Owlstone Medical aims to evaluate one such EVOC probe strategy based on the administration of the probe OWL-EVO1.
The Evolution study consist of a phase 1a in which the safety and pharmacokinetics of OWL-EVO1 are assessed; in this part of the study up to 21 healthy volunteers will be recruited. In this phase 1a the probe will be administered for the first time in humans in a single ascending dose design. 5 different doses of the probe are planned to be administered across 5 different cohorts. This part of the study will be conducted at a Phase 1 unit in Belgium. Participating subjects will be administered a dose of the EVOC probe; up to 8 breath samples, using Owlstone's RECIVA, will be collected in a 24h wash-out.In the subsequent second phase 1b, research will aim to identify the most optimal dose and timing of the breath test to maximise the discriminative signal between lung cancer patients (cases) and healthy controls. Up 50 cases and 50 controls will be recruited in selected sites in U.K.; the Phase 1b has been designed as an adaptive trial design. Participating subjects will be administered the probe and will provide up to 7 breath samples over a 240min wash-out.
This study is intended to provide proof of concept for the use of OWL-EVO1 as probe for breath-based detection of lung cancer.
This will be an important step towards realizing a breath-based screening approach for lung cancer.
Summary of Results
The Evolution trial was a clinical trial sponsored by Owlstone Medical Ltd, a biotechnology company based in Cambridge, UK. Owlstone Medical’s mission is to develop a breathalyser that can detect disease at early stages, to allow for earlier treatment, saving lives and reducing healthcare costs.Previous research has shown that if a certain product (referred to as a “probe”) is administered, it may be processed differently in your body if you are healthy, compared to if you have a particular disease. The Evolution trial used a probe called OWL-EVO1, which has previously shown that it may only be broken down in people with lung cancer and not in healthy people. In the Evolution trial, OWL-EVO1 was administered to people with and without lung cancer to assess the accuracy of the breath test to tell the difference between these two groups.
The Evolution trial was split into two phases: Phase 1a and Phase 1b. In the Phase 1a trial 21 healthy volunteers received the probe at a clinical trials unit. These participants were split into 5 different cohorts, with each cohort receiving a different dose of the probe. Participants were monitored for any medical problems related to the probe for 24 hours at the clinical trials unit and for an additional seven days via telephone. Doses were tested from low to high, after a cohort was complete a safety evaluation was performed before moving onto the next cohort at a higher dose. The participants also gave multiple breath samples- one before receiving the probe and then at multiple timepoints after receiving the probe.
In the Phase 1b trial, 29 healthy volunteers and 14 participants who had been diagnosed with lung cancer took part, at two different NHS hospitals in England. All participants were monitored for the development of medical problems for four hours after receiving the probe at hospital, and for seven days afterwards by telephone. Again, the participants gave breath samples once before receiving the probe and at up to six timepoints after receiving the probe.
Over the Phase 1a and 1b trials, only four medical problems were assessed as being related to the probe, three of which were mild, and all resolved without any ongoing issues. None of the problems were classified as being serious.
Although the main purpose of the study was to prove safety, the goal of the analysis of the breath samples was to see if the probe reporter is detectable on the breath of people with lung cancer, and not on healthy controls. The results from showed that the reporter was detectable on breath, however at the dose given in Phase 1b it was detectable on breath from both the participants with lung cancer and the controls.
Overall, this study has shown that giving OWL-EVO1 intravenously is safe, and that it is possible to detect the probe reporter on breath. The results of this study allowed Owlstone to move onto a Phase 2 trial, where the probe is being administered at different doses to a wider population of patients, to find the optimum dose that allows us to tell the difference between people with and without lung cancer. More information can be found here: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT06193239%2FNBTI%2FA-y6AQ%2FAQ%2F709a7bab-b36b-4f84-9df0-6231698dad04%2F2%2F-zocCyYiKK&data=05%7C02%7Criverside.rec%40hra.nhs.uk%7C6821da7affb4479adcae08dd3ef4e6bb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638735943736200272%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=kmbbfWZ7%2F1QklEeH0sJf26FO7dQbL0QKxjNobpDx8Zo%3D&reserved=0
We would like to take this opportunity to thank all participants who took part in Evolution. This study was a crucial part in developing a breath test to detect lung cancer, and could not have happened without the participants.
REC name
London - Riverside Research Ethics Committee
REC reference
20/LO/1184
Date of REC Opinion
1 Dec 2020
REC opinion
Further Information Favourable Opinion