HTL0018318/AGN-242071 Health Testing Programme
Research type
Research Study
Full title
Health testing with all subjects who participated in any phase I clinical study and received at least one dose of HTL0018318/AGN-242071 to date.
IRAS ID
262716
Contact name
Steve Jones
Contact email
Sponsor organisation
Heptares Therapeutics Limited
Duration of Study in the UK
1 years, 2 months, 30 days
Research summary
Research Summary\nHTL0018318 is a selective muscarinic M1 receptor agonist under clinical investigation as a potential new symptomatic treatment for cognitive impairment in patients with Alzheimer’s disease and dementia with Lewy bodies. HTL0018318 initially entered early phase clinical trials after all necessary pre-clinical studies in animals were conducted and passed successfully. An additional toxicity study in non-human primates (monkeys) was investigating different dosing levels of HTL0018318 over a 9-months period to enable longer duration studies in humans in the future, as is common practice. The sponsor Heptares Therapeutics Ltd became aware of an important emerging safety finding of a neoplastic, rare tumour, in some of the monkeys in the toxicity study. This was observed at doses and durations of dosing exceeding those used in the clinical trials in human subjects to date. The sponsor voluntarily suspended clinical development activities of HTL0018318. The suspension was not based on any human findings. \n\nThe sponsor is informing subjects who received any dose so far of the drug HTL0018318 and invites subjects to the present Health Testing Programme as subjects’ safety is of the utmost importance. The programme is a precautionary approach and its purpose is to establish a baseline of subjects’ health status by doing two separate visits, both consisting of: general health blood tests and a liver ultrasound, as well as a single optional genetic testing. The two visits will be separated by six to eight months. All results will be communicated to subjects as soon as available. The investigator will organise follow-up if abnormal tests are observed based on the local best medical practice. The sponsor is investigating the findings in the monkeys and will communicate new relevant data to the investigators in a timely fashion.\n\nSummary of Results\nThis health testing programme was designed to provide health testing procedures to all subjects who had participated in any Phase 1 clinical study with a drug (HTL0018318, also referred to as AGN-242071) and had received at least 1 dose of HTL0018318/AGN-242071. \nA non-human primate 9-month toxicology study, which is a study to help determine drug safety, showed a high concentration of the study drug and the possibility of developing a very rare type of cancer (haemangiosarcoma). As the risk of haemangiosarcoma in subjects who had previously taken the drug is unknown; therefore, this 6-month programme provided targeted health testing, including blood tests for indicators of general health and liver ultrasound (as the liver was the primary target for haemangiosarcoma in the toxicology study).\nIn this health testing programme, 201 subjects were enrolled on this programme. They received health assessments on 2 occasions, at least 6 months apart (no less than 6 months and no longer than 8 months). Assessments at Initial Visit and at the 6-month visit included liver ultrasound, blood tests and the occurrence of any adverse events (AEs)/serious adverse events (SAEs).\nResults from liver ultrasound assessments and laboratory test results did not reveal any changes suggestive of an impact of treatment with HTL0018318/AGN-242071 on the health of the liver and no results indicated malignant hepatic changes. In addition, no AEs reported during the health testing programme were considered related to previous treatment with HTL0018318/AGN-242071.\nData collected in this health testing programme did not indicate any changes in the general health or status of the liver of subjects who had previously received HTL0018318/AGN-242071.\n\n
REC name
London - London Bridge Research Ethics Committee
REC reference
19/LO/0512
Date of REC Opinion
5 Apr 2019
REC opinion
Favourable Opinion