NCT04311515

To Evaluate Safety, Tolerability and Pharmacological Effects of PU AD in Subjects With Mild AD Dementia

A Phase 2A Study to Evaluate Safety, Tolerability and Pharmacological Effects of PU AD in Subjects With Mild Alzheimer's Disease (AD) Dementia

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: Samus Therapeutics, Inc. · Industry
• Sex: All
• Age: 55 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The study is designed as a classic, randomized, double blind, placebo controlled, parallel group study including one active dose of PU AD and matching placebo, designed to assess safety, tolerability and pharmacological effects of oral PU AD (dihydrochloride salt) in subjects with mild AD

Detailed description

This is a multicenter, randomized, double blind, placebo controlled, parallel group Phase 2A study with one active dose of PU AD and matching placebo, once daily (qd), designed to assess safety, tolerability and pharmacological effects of oral PU AD (dihydrochloride salt) in subjects with mild AD. This study will be performed at up to 50 clinical sites in the US and approximately 150 subjects are expected to participate in this study, with 75 subjects in each treatment arm randomized 1:1. Subjects with mild AD meeting all inclusion criteria and none of the exclusion criteria are eligible to participate in this study. The study consists of a Screening Period (including Pre treatment) (4 weeks), Treatment Period (24 weeks), and a safety Follow up visit (within 30 days \[±7 days\] after the last dose of IMP). The expected study duration is 24 Months. The Screening Visit and Pre treatment Visit will take place within 4 weeks of dosing to assess eligibility of subjects. Enrolled subjects will return to the site for randomization and baseline assessments at Week 1. Subjects will be randomized with a 1:1 ratio to one of two treatment arms: 30 mg PU AD or matching 30 mg placebo qd. During the 24 Week Treatment Period, subjects will be administered 30 mg PU AD or matching 30 mg placebo qd, orally. According to investigator's clinical judgement, subjects experiencing intolerable AEs, if medically necessary, may be allowed to adjust the dose regimen from 30 mg qd to 30 mg every other day (qod), with approval by the medical monitor. If patients still cannot tolerate the adjusted dose regimen, the investigator must discuss early termination with the medical monitor. Subjects will return to the site at Week 2, Week 4, Week 6, Week 12, Week 18, and Week 24 for study assessments as specified PK sampling time points are specified in and will support a population PK model. . Any subject who discontinues prior to completion of the study, and reached 12 weeks of treatment should have all scheduled assessments of the Week 24/Early Termination (ET) Visit completed. All subjects will return to the site for a Follow up Visit, within 30 days (±7 days) after the last dose of study for safety assessments at the Week 28/End of Study (EoS) Visit

Conditions

• Alzheimer Disease

Interventions

Type	Name	Description
RADIATION	Tau Positron emission tomography (PET)	Tau PET imaging enables the longitudinal assessment of the spatial pattern of tau deposition. Tau accumulates with progression of AD dementia and may be sensitive to disease related changes, particularly those due to intervention with a drug thought to work through a tau related mechanism. Quantitative assessments will be utilized to evaluate the target engagement and pharmacological effects of PU-AD after 6 months of treatment
RADIATION	Fluorodeoxyglucose (FDG) Positron emission tomography (PET)	Measurement of neuronal function with FDG PET can help to understand the relationship between target engagement and potential clinical effects. FDG PET will be acquired using stringent quality control. Since glucose metabolism captures all neuronal activity, in order to isolate effects due to treatment, patients will be maintained in a consistent state during the tracer uptake period. Subject motion during image acquisition will be minimized and monitored. Images will be quality controlled, processed, and measured quantitatively using methods that maximize signal to noise associated with technical and physiologic variability
DIAGNOSTIC_TEST	Cerebrospinal fluid (CSF) Biomarkers	A broad set of biomarkers are being assessed in this study to indicate whether this treatment is able to impact multiple pathways associated with AD related to neurodegeneration
DIAGNOSTIC_TEST	Blood Biomarkers	Changes in blood biomarkers may be observable if treatment affects cerebral amyloidosis and loss of nerve cells
BEHAVIORAL	Rating Scales	Alzheimer's Disease composite score (ADCOMS+), CDR sb, Alzheimer's Disease Assessment Scale Cognitive (ADAS cog), Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS ADL), Mini Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale Cognitive (ADAS-COG 12)
DRUG	PU-AD	PU-AD 30mg daily for 6mos
DRUG	Placebo	Placebo 30mg daily for 6mos

Timeline

• Start date: 2020-06-30
• Primary completion: 2020-09-09
• Completion: 2022-11-15
• First posted: 2020-03-17
• Last updated: 2022-11-17

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study