Date: 2018-01-18
Type of
information: Results
phase: 2
Announcement: interim results
Company: Axovant Sciences (USA - NY)
Product: nelotanserin
Action
mechanism:
- 5-HT2A receptor inverse agonist. Nelotanserin is an investigational drug candidate that has the potential to be a best-in-class, once-daily, orally-administered, potent and highly selective inverse agonist of the 5HT2A receptor. The 5HT2A receptor biology is associated with motor symptoms and neuropsychiatric disturbances including visual hallucinations – a common occurrence in patients with Lewy body dementia. Axovant is developing nelotanserin to address multiple aspects of Lewy body dementia.
- Nelotanserin was discovered by Arena Pharmaceuticals.
Disease: Lewy Body dementia
Therapeutic
area: Neurological diseases - CNS diseases
Country: USA
Trial
details:
- This study seeks to evaluate safety and efficacy of nelotanserin for the treatment of visual hallucinations in subjects with Lewy body dementia. This multi-center, randomized, double-blind, placebo-controlled, pilot Phase 2 crossover study evaluated the safety, tolerability, and efficacy of nelotanserin over a four-week treatment period and enrolled 30 patients with DLB and PDD who were experiencing frequent and recurrent visual hallucinations. With the crossover design, every patient received placebo for four weeks and nelotanserin for four weeks (two weeks of a 40 mg dose followed by two weeks of an 80 mg dose). Study participants were allowed to be on stable antipsychotic treatments, stable anti-Parkinson’s disease treatments, and stable background cholinesterase inhibitor therapy for at least four weeks prior to screening.
- The prespecified primary endpoint of the pilot study was safety including assessment of extrapyramidal symptoms as measured by the change in UPDRS scores. In addition, there were multiple exploratory efficacy assessments in the study that included UPDRS Part III, SAPS, SAPS-PD, PGIC-VH and an internally developed patient diary, that evaluated the effects of nelotanserin over a four-week treatment period. Individuals who completed this study were eligible to receive nelotanserin in an extension study. (NCT02640729)
Latest
news:
- • On January 8 , 2018, Axovant Sciences announced that its investigational drug nelotanserin met its prespecified primary endpoint of safety in the pilot Phase 2 Visual Hallucination study. In addition, in this exploratory study, nelotanserin treatment resulted in a positive trend in efficacy in a prespecified intent to treat (ITT) analysis of the motor function scale, the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III. Nelotanserin treatment also resulted in an efficacy signal in a post-hoc subset analysis of patients with higher baseline scores on the Scale for the Assessment of Positive Symptoms – Parkinson’s Disease (SAPS-PD).
- In the pilot study of nelotanserin in patients with DLB and Parkinson’s disease dementia (PDD) who were experiencing visual hallucinations, the primary endpoint was safety, including an assessment of symptoms as measured by the UPDRS. On this primary endpoint, nelotanserin was generally well tolerated. A number of exploratory efficacy assessments were conducted, including the UPDRS Part III; the Scale for the Assessment of Positive Symptoms (SAPS); SAPS-PD; the Patient Global Impression of Change of Visual Hallucinations (PGIC-VH); and an internally developed patient diary. In a prespecified ITT analysis, nelotanserin treatment versus placebo (n=27) resulted in a 3.12 point improvement in the UPDRS Part III with a positive trend (p=0.075, unadjusted). Notably, in a prespecified analysis of the DLB patient subset (n=19), nelotanserin improved the UPDRS Part III by 4.00 points (p=0.041, unadjusted).
- Although nelotanserin did not significantly improve the SAPS-PD (n=27) in the entire efficacy evaluable population (0.88 point improvement, p=0.519, unadjusted), in a post-hoc subset analysis of patients with a baseline SAPS-PD score greater than 8.0 (n=19), indicating greater severity, nelotanserin treatment at 40 mg for two weeks followed by 80 mg for two weeks resulted in a 1.21 point improvement (p=0.011, unadjusted). Further analyses of these data will be conducted which could yield new insights into the effects of nelotanserin. No other trends of improvement were seen on the full SAPS, PGIC-VH, or in the patient diary.
- • On February 13, 2017, Axovant Sciences announced preliminary results from the planned interim analysis of the first 11 patients to complete its Phase 2 study of nelotanserin in Lewy body dementia patients. Based on these interim results, Axovant plans to expand patient recruitment in this study and will begin preparations for a Phase 3 registration program expected to start in the second half of 2017. The ongoing Phase 2 study includes patients with either dementia with Lewy bodies (DLB) or Parkinson's disease dementia (PDD) who experience frequent visual hallucinations with a score of 18 or higher on Mini Mental State Examination (MMSE). This is a double-blind, randomized, placebo-controlled, cross-over design study involving random assignment of patients to a treatment sequence of either placebo followed by nelotanserin or nelotanserin followed by placebo. Treatment periods are 4 weeks each with a 4-week washout period between treatment periods. During the active treatment period, patients receive 40 mg nelotanserin during the first 2 weeks and 80 mg nelotanserin during the subsequent 2 weeks.
- The primary outcome measures of the study were extrapyramidal signs as assessed by Unified Parkinson's Disease Rating Scale (UPDRS) Parts II + III and safety. UPDRS Parts II + III was measured at baseline and at the end of each 4-week treatment period. Secondary outcome measures included observational changes in the severity and frequency of visual hallucinations, including multiple subscales from the Scale for the Assessment of Positive Symptoms (SAPS). SAPS subscales were measured at baseline, at week 2, and at week 4 of each treatment period.
- Pre-specified primary endpoints: The mean change from baseline in the UPDRS Parts II + III exhibited statistically significant improvements (p-value < 0.05) for nelotanserin relative to placebo. This result is consistent across least squares and observed mean changes. Safety analysis included measurement of the incidence of adverse events. There were no reported drug-related serious adverse events, and there were no adverse events that led to discontinuation of the study medication.
- Secondary endpoints: Secondary endpoints evaluated efficacy on multiple subscales from the SAPS including SAPS-PD, SAPS-PD-H, and SAPS-H. Axovant evaluated an internally developed, proprietary secondary endpoint to measure episodes of hallucinations using a patient diary. In this interim analysis, these secondary endpoints did not demonstrate statistically significant differences for nelotanserin relative to placebo.
- Based on these preliminary results, Axovant plans to expand patient recruitment to confirm the treatment benefits observed in the interim results from this ongoing study. Axovant expects the full study to complete in mid-2017 and plans to present detailed results at a scientific meeting in 2017. In addition, Axovant is exploring nelotanserin as a potential treatment for REM Sleep Behavior Disorder (RBD) in patients with dementia with Lewy bodies. The company expects results from the RBD study in the second half of 2017.
- Based on the results of these two studies Axovant plans to commence a Phase 3 registration program in the second half of 2017. As part of its preparations, the company expects to evaluate UPDRS Parts II + III as a potential endpoint for Lewy body dementia patients in Phase 3.
Is
general: Yes
