A phase IIa study investigating neflamapimod in Huntington Disease V1
Research type
Research Study
Full title
A Double-Blind, Placebo-Controlled Two-Period 10-Week Treatment Within-Subject Crossover Study Of Cognitive Effects Of Neflamapimod in Early-Stage Huntington Disease (HD)
IRAS ID
261197
Contact name
Roger Barker
Contact email
Sponsor organisation
EIP Pharma, Inc.
Eudract number
2018-004840-51
Clinicaltrials.gov Identifier
125198, IND number
Duration of Study in the UK
1 years, 4 months, 30 days
Research summary
Research Summary:
In this research study, a new drug named neflamapimod will be tested for the treatment of learning and memory problems associated with early stage Huntington's Disease (HD).This is a double-blind, placebo controlled, within-subject crossover research study to learn about the safety and clinical effects of taking neflamapimod or placebo for the treatment of learning and memory problems in subjects with early stage HD.
Patients will be subjects aged 30 to 70 years with genetically confirmed early stage HD and identified cognitive deficits.
This study will include two groups, neflamapimod and placebo in each treatment period.
The patients will take the study drug (placebo or neflamapimod) in the form of capsules by mouth, twice a day, for two treatment periods lasting 10 weeks each.
The patient's participation may last up to 9.25 months. The patients will need to visit the clinic 7 times within 15 weeks during Treatment Period 1, and 6 times within 10 weeks during Treatment Period 2 and for the Follow-up Visit 14 days (± 3 days) after the last dose of study drug. There will be an 8-12 week washout period between Treatment Periods 1 and 2 during which the patients will have 1 study visit occurring 2 weeks after the last dose of study drug in Treatment Period 1.The study is sponsored by EIP Pharma, INc based in USA and patients will be recruited in the United Kingdom.
Summary of Results:
The EIP19-NFD-401 study was intended to be a within subject crossover study to evaluate the cognitive effects of neflamapimod treatment in subjects with early stage Huntington’s Disease. This means each subject would be randomly assigned to receive either neflamapimod or placebo in the first treatment period of 10 weeks, then after 8-10 weeks of washout (no study drug consumed) the subject would then be assigned to the opposite treatment regimen (i.e. those who took placebo in the first treatment period would then take neflamapimod in the second treatment period, etc) in the second treatment period of 10 weeks.
The study was unable to be completed as intended due to the premature termination of the study. Due to the coronavirus disease 2019 (COVID-19) pandemic all clinical research in the United Kingdom was halted in March 2020. Accordingly, any ongoing treatment was discontinued immediately and this study was interrupted at that time. At the time the study was interrupted, two subjects were in Treatment Period 1. All other subjects who remained in the study were halted either during the washout period or within 2 weeks of starting Treatment Period 2, with the exception of 1 subject who completed Treatment Period 2 remotely.
Sponsor ultimately elected to terminate the study on 15 October 2020 both due to the ongoing COVID-19 pandemic as well as new data from a completed study that indicated the dosing regimen (40 mg, twice daily) was unlikely to demonstrate efficacy.
Since only one subject completed, the efficacy analysis compared the outcomes of subjects who received neflamapimod with those who received placebo in the first treatment period only. No significant differences between neflamapimod and placebo were seen with regard to the following assessments: virtual Morris Water Maze (vMWM); Unified Huntington’s Disease Rating Scale (UHDRS); or most tasks included in the Cambridge Neuropsychological Test (CANTAB). Statistically significant differences between neflamapimod and placebo were seen in the following CANTAB tasks: One Touch Stockings of Cambridge (OTS) ; increase in latency to correct errors in neflamapimod vs. placebo) and Spatial Span (SS; increase in forward span length in neflamapimod vs. placebo ); however, the results are inconsistent, as those in the OTS reflect apparent worsening, while those in the SS reflects apparent improvement in cognitive function.
Neflamapimod was well tolerated in this study with no new safety signal identified. There were 11 Adverse Events (AEs) reported in 9 subjects. The only AE reported in more than 1 subject was common cold. All AEs were reported as mild. Two AEs (1 case each of abdominal pain and nausea) were considered by the Investigator to be related to the study drug, however, both of these events occurred in subjects who were receiving placebo.REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
19/EE/0137
Date of REC Opinion
26 Jun 2019
REC opinion
Further Information Favourable Opinion