Further primary and secondary endpoint analysis of Neurotech\u2019s Phase 1\/2 trial has highlighted additional benefits
\nNTI164 is the first broad-spectrum cannabinoid drug therapy to show significantly clinical improvement in Rett Syndrome patients
\nAll 14 female paediatric patients extended to 52 weeks, with ongoing data to be collected and reported <\/p>\n
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Special Report: Neurotech International has reported further primary and secondary endpoint analysis of its Phase 1\/2 trial NTIRTT1 showing significant additional benefits in Rett Syndrome girls after 12 weeks of daily oral treatment with its broad-spectrum cannabinoid drug therapy NTI164. <\/strong><\/p>\n On April 17, clinical-stage biotech\u00a0Neurotech International (ASX:NTI)\u00a0<\/strong><\/a>reported top-line results for the Phase 1\/2 Rett Syndrome clinical trial<\/a> with NTI164 being the first broad-spectrum cannabinoid drug therapy to show a statistically significant clinical improvement in Rett Syndrome patients.<\/p>\n Rett Syndrome is a rare genetic neurological and developmental disorder and is almost exclusively the result of a mutation or mutations in the methyl CpG binding protein 2 (MECP2) gene located on the X chromosome, which is required for normal brain development and function.<\/p>\n The syndrome occurs almost exclusively in girls, with an incidence of one in 10,000 female live births with the prevalence of ~15,000 girls and women in the US and 350,000 globally.<\/p>\n The Rett Syndrome market is estimated at more than US$2bn annually.<\/p>\n The NTIRTT1 trial involved 14 female paediatric patients with an average age of 8.8 years and weight of 27.5kg with a Rett Syndrome Behavioural Questionnaire (RSBQ) mean measure of 44.6 and CGI-severity of illness (CGI-S) measure of 4.6.<\/p>\n The trial participants underwent a 12-week daily oral treatment regimen with NTI164\/placebo required for primary endpoint analysis.<\/p>\n The Clinical Global Impression \u2013Improvement (CGI-I) at 12 weeks versus baseline on four core Rett-anchors highlighted 93% of patients improved with 36% \u201cvery much\/much improved\u201d.<\/p>\n The key secondary endpoint of the RSBQ showed a mean difference of -13.4 versus baseline and a 205% improvement from week four to week 12.<\/p>\n All 14 female paediatric patients have been enrolled in the 52-week extension phase of the trial, with ongoing data to be collected and reported.<\/p>\n \u00a0<\/p>\n Clinical Global Impression (CGI) is a physician\/observer-rated scale of the clinician\u2019s impression of the global state of an individual and is frequently employed in clinical trials for neuropsychiatric disorders.<\/p>\n CGI-I is a 7-point scale requiring the clinician to assess how much the patient\u2019s illness has\u00a0 improved or worsened relative to a baseline state at the beginning of the intervention and ranges from 1 \u2013\u201cVery Much Improved\u201d to 7 -\u201cVery Much Worse\u201d.<\/p>\n Top-line primary endpoint analysis reported on April 17 showed a statistically significant improvement in CGI-I at 12 weeks versus baseline measures.<\/p>\n NTI says the top-line CGI-I results were based on analysis available on four Rett-specific assessments (anchors) from a total of nine Rett-specific measures.<\/p>\n As it was the first in human study of NTI164 in Rett, NTI examined other anchors (sub-domains) to further understand which showed improvements that could be targeted in registration-directed trials.<\/p>\n NTI says in late-stage clinical trials typically 2-3 sub-domains are examined for CGI-I.<\/p>\n With the complete data set now available for analysis, NTI reports further improvement in CGI-I versus baseline.<\/p>\n Of the 14 Rett Syndrome patients as measured by CGI-I across all nine Rett-specific measures, 50% of patients showed improvement at 12 weeks with NTI164.<\/p>\n NTI says 50% were minimally improved, 43% showed no change and one patient (7%) was minimally worse.<\/p>\n \u00a0<\/p>\n\n Image supplied by NTI<\/em><\/p>\n \u00a0<\/p>\n NTI has undertaken an analysis of those specific sub-domains cited by doctors and caregivers as important and where NTI164 showed strong improvements.<\/p>\n The drug has shown statistically significant improvements across communication skills, mental alertness, socialisation\/eye contact and anxiety, which will likely form the basis of CGI-I measures for registration-directed studies.<\/p>\n \u00a0<\/p>\n\n Image supplied by NTI<\/em><\/p>\n \u00a0<\/p>\n NTI says RSBQ consists of 45 items, rated as 0 = \u2018not true\u2019, 1 = \u2018somewhat or sometimes true\u2019 or 2 = \u2018very true\u2019, that can be grouped into eight symptom domain subscales graded on a scale of 0\u201390 (maximum severity).<\/p>\n The company says eight domains\/subscales that reflect the core features of Rett were examined.<\/p>\n The trial showed patients receiving NTI164 had a 205% improvement in their mean baseline change from week 4 (-4.4) to week 12 (-13.4).<\/p>\n Overall, NTI says a clinically meaningful 30% decrease in the patients\u2019 mean RSBQ total score at 12 weeks was seen, which was strongly statistically significant.<\/p>\n At start of the trial the average RSBQ total score for the patients was 44.6 compared to 31.2 at 12 weeks.<\/p>\n \u00a0<\/p>\n\n Image supplied by NTI<\/em><\/p>\n \u00a0<\/p>\n Another key secondary endpoint \u2013 CGI-S \u2013 reflects a clinician\u2019s impression of severity of illness on a 7-point scale ranging from 1=not at all to 7=among the most extremely ill. It also showed a statistically significant improvement.<\/p>\n The study also met other key secondary endpoints including Impact of Childhood Neurologic Disability Scale versus baseline and Rett Syndrome Caregiver Burden Inventory.<\/p>\n \u00a0<\/p>\n NTI says one serious adverse event was reported during the 12 week treatment period, with development of urticaria (hives ) in one patient.<\/p>\n The company says Urticaria has not been previously observed in any previous and ongoing studies of NTI164.<\/p>\n Zero patients reported diarrhoea, while nausea\/vomiting occurred in two patients. The mean weight of patients was largely unchanged at 12 weeks (0.3 kg gain) versus baseline, indicating overall no weight loss during the treatment period.<\/p>\n None of the adverse events required any additional medications. Measurements pertaining\u00a0 to kidney and liver function along with blood chemistries and vital signs were normal over the 12 weeks.<\/p>\n NTI says NTI164 exhibits an excellent safety profile, with minimal patient-specific side-effects in Rett Syndrome patients.<\/p>\n \u00a0<\/p>\n Principal trial investigator and senior staff specialist at The Children\u2019s Hospital at Westmead, Sydney\u2019s Children\u2019s Hospital Network Associate Professor Carolyn Ellaway, is pleased with the trial results.<\/p>\n \u201cThe NTIRTT1 clinical trial is the first time a broad-spectrum cannabinoid drug therapy (NTI164) has demonstrated significant patient improvements in Rett Syndrome using validated clinical measures including CGI-I and RSBQ,\u201d she says.<\/p>\n \u201cOur data is very encouraging as we have observed clinically meaningful improvements in those symptoms repeatedly deemed as most important for treating clinicians, caregivers, and patients; notably communication, hand behaviours, anxiety\/mood, and quality of life.<\/p>\n \u201cThese benefits have not compromised patient safety, with NTI164 displaying an excellent safety profile over the 12 weeks of the trial.\u201d<\/p>\n Rett Syndrome is the third neurological disorder in children where NTI164 has shown a statistically significant clinical benefit, alongside autism and PANDAS\/PANS.<\/p>\n \u201cThis fulsome data set reported today represents a very rapid translation of our strong\u00a0\u00a0 conviction on the anti-neuroinflammatory and neuroprotective effects of NTI164 applied to a third paediatric neurological population, Rett\u00a0 Syndrome, where safe and effective therapies are urgently needed,\u201d NTI executive director Dr Thomas Duthy says.<\/p>\n \u201cThe level of improvement we have observed in these girls after 12 weeks of treatment is remarkable in the context of the excellent safety profile of NTI164 where just a single serious event was recorded and adverse events were minor and manageable relative to the observed standard therapy in the United States,\u201d he says.<\/p>\n \u201cWe look forward to updating the market on these girls\u2019 progress as they progress through the 52 week extension under A\/Prof\u00a0 Ellaway\u2019s supervision and presentation of these results at the upcoming 9th World Rett Congress, to be held in Australia later this year.\u201d<\/p>\n A caregiver of a patient in the NTIRTT1 trial said: \u201cShe seems much more in tune to what\u2019s going on around her, e.g. patting the dog (has never done this before).\u201d<\/p>\n Another caregiver said: \u201cShe uses eye pointing, sometimes brings food\/drink to an adult \u2013this has not happened before.\u201d<\/p>\n \u00a0<\/p>\n This article was developed in collaboration with Neurotech International, a Stockhead advertiser at the time of publishing. <\/em>\u00a0<\/em><\/p>\n This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.<\/em><\/p>\n <\/span><\/p>\n The post Neurotech reports more positive Phase 1\/2 Rett Syndrome clinical trial results<\/a> appeared first on Stockhead<\/a>.<\/p>","protected":false},"excerpt":{"rendered":"Improvement in primary endpoint \u2013 CGI-I <\/strong><\/h2>\n
Strong improvements in core anchors<\/strong><\/h2>\n
Secondary Endpoint \u2013 RSBQ<\/strong><\/h2>\n
A single adverse safety event<\/strong><\/h2>\n
Promising results <\/strong><\/h2>\n