Lysakare infusion in GEP-NET patients
Research type
Research Study
Full title
A multicenter, open-label post authorization safety study to evaluate the effect of LysaKare® infusion on serum potassium levels in GEP-NET patients eligible for lutathera® treatment.
IRAS ID
292840
Contact name
Professor Martin O. Weickert
Contact email
Sponsor organisation
Advanced Accelerator Applications (A Norvatis company)
Eudract number
2019-004073-76
Duration of Study in the UK
1 years, 5 months, 15 days
Research summary
In this study patients suffering from GEP-NET and who are eligible for Lysakare® treatment will be infused with a 25g solution of Lysakare® (medication that's already received marketing authorisation from EMA) in a bid to evaluate the effect of the drug on their serum potassium levels. Monitoring will be done via a systematic assessment of serum potassium levels will be performed during infusion and up to 24 hours post start of infusion compared to baseline. The study also hopes to confirm the safety profile of Lysakare® on GEP-NET patients who are eligible for Lysakare® but are not taking it. They will not be taking in during the study.
The study will take place across many different centres, with all individuals involved aware of the drug being handled. The aim is to recruit 40 patients suffering from GEP-NET to receive one infusion with LysaKare®. The patient will have a screening period (between 1-7 days) during the study, to determine eligibility, followed by an infusion day (Lysakare® administered intravenously over a period of 4 hours) with an optional overnight in-clinic stay, and a follow up call (48 hours post dosing). The patients condition will be monitored for 12 hours for adverse event (AE) evaluations. In case any AEs are noted, the infusion will be stopped and patient treated.
If the patient does not wish to spend a night at the facility, they will be free to leave after the 12 hour assessment and return for their 24 hour assessment. Patient will not be able to have a repeat Lysakare® infusion for at least 7 days post dose. During that time they may start treatment with Lysakare®.Lay summary of study results:
Study CAAA001A12401 was a multi-center open-label Post-Authorisation Safety Study (PASS) to evaluate the effect of LysaKare infusion on serum potassium levels in gastroenteropancreatic neuroendocrine tumors (GEP-NET) subjects eligible for Lutathera treatment. Eligible subjects were dosed with LysaKare solution for infusion of 1,000 mL without co-infusion of Lutathera. A total of 42 subjects were enrolled across 7 active centers in Great Britain (4 centers), Italy (1 center), Netherlands (1 center), and Poland (1 center). Among them, 1 subject was not treated as per subject’s request. The median age of subjects was 57.0 years and ranged from 34 to 79 years. Overall, LysaKare infusion duration and total volume administered were completed per planned study design for the 41 treated subjects. The primary objective of the study was to assess the effect of LysaKare administration on serum potassium concentrations and the primary endpoint was the mean of change in the serum potassium levels at 2, 4, 6, 8, 12 and 24 hours after LysaKare intravenous administration compared to baseline. The mean change in serum potassium peaked at 4h post-dose with a mean (Standard Deviation, SD) of 0.60 (0.666) mmol/L then gradually returned to pre-dose level 24h post-dose with a mean (SD) of 0.07 (0.396) mmol/L. These results were supported by robust conclusion from the mixed model repeated measures analysis. The mean (SD) maximum change in serum potassium level recorded was 0.82 (0.61) mmol/L (range: -0.6-2.6 mmol/L) and the median time to this maximum change was 4.3 hours (range: 2-24 hours). The supplementary analysis indicated that similar to serum potassium, effects of LysaKare infusion on other electrolytes (bicarbonate, sodium, chloride) and blood gas components (pH, lactate, partial pressure of carbon dioxide) had globally a similar pattern of transient change that lasted around 24 hours. Based on the safety data collected during the study, there were no Serious Adverse Events (SAEs), no deaths, and no Adverse Events (AEs) leading to treatment discontinuation or interruption in this study. A total of 11 subjects (26.8%) experienced at least one AE during the study. The most frequently reported AEs were hyperkalemia (12.2%) and nausea (4.9%). A total of 6 subjects (14.6%) reported treatment-related AE: hyperkalemia (5 subjects (12.2%), of which one of Grade 3, and vomiting in 1 subject (2.4%). All hyperkalemia events resolved either naturally (in 3 cases) or with conservative treatments (2 cases) within the same day. The most frequent post-dose laboratory abnormalities, irrespective of baseline values, were hyperkalemia (41.5%), hyponatremia (41.5%) and anemia (31.7%). Most laboratory abnormalities were in low grade. There was one Grade 3 hematologic abnormality (lymphocyte count decreased) observed in 1 subject, and one Grade 3 increase of serum potassium occurred in 1 subject. Electrolytes and blood gas laboratory values indicated a general trend of metabolic acidosis that developed and was resolving within 24 hrs after Lysakare administration. No AEs of metabolic acidosis were reported in the study. There were no notable vital sign abnormalities reported in this study and none of the notable electrocardiogram (ECG) abnormalities was considered to be clinically significant. In conclusion, based on laboratory data transient hyperkalemia occurred in 41.5% of participants. Potassium increase was manageable, and on average it peaked at 4 hours after the beginning of LysaKare infusion and resolved within 24 hours. Based on the safety data collected during the study, no new safety signals attributable to LysaKare have been identified in this population of adult subjects. Further details regarding the study are available via the link: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT03972488%253Ftab%253Dresults%2526a%253D28.%2FNBTI%2FNhK5AQ%2FAQ%2F144d6da7-44ff-4108-b5d4-1f1a9a96b38a%2F3%2F8QNFbnfoBY&data=05%7C02%7Ccoventryandwarwick.rec%40hra.nhs.uk%7Cb353ecf802eb4893cb9e08dcfa884d33%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638660710513994560%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=UU2ZOT%2Fm1yJLx%2FsWwoN1F8c4ycLeex3Vp4%2FDurGwfCs%3D&reserved=0REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
21/WM/0021
Date of REC Opinion
19 Mar 2021
REC opinion
Further Information Favourable Opinion