Alzheimer's disease (AD) is the most common form of dementia. In the brains of people with AD, certain small substances stick together. This leads to changes in thinking and behaviour. The company PRInnovation is developing a new treatment for Alzheimer's disease, called PRI-002. It is thought that PRI-002 can cut the sticked substances back into small pieces. That would reduce the effects of Alzheimer's disease. In the current study the investigators examine whether PRI-002 is safe and effective in participants with mild cognitive impairment (MCI) or mild dementia due to AD.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. The post-mortem pathology of AD is mainly characterised by neurodegeneration as well as extracellular amyloid plaques and intracellular neurofibrillary tangles. Research suggests that the amyloid-β-peptide (Aβ) aggregation plays a major role in the development of AD, while Aβ oligomers are thought to be the most toxic species. Therefore, various strategies to develop AD therapeutics address Aβ and some examples include trying to reduce its formation, inhibit its aggregation to fibrils or enhancing its clearance. PRI-002 is being investigated as a possible treatment for cognitive impairment due to AD. PRI-002 is an all D-amino acid peptide (all-D-peptide) consisting of a rationally designed primary structure, resulting in efficient removal of Aβ oligomers. PRI-002 specifically aims to eliminate neurotoxic Aβ oligomers by disassembling prion-like behaving Aβ oligomers into non-toxic Aβ monomer units. This therapeutic principle is new and unique and differs from that of other amyloid related drug candidates currently in clinical development, which aim to increase the degradation rate of different Aβ species. The current trial is a Phase 2 proof-of-concept study to further investigate the safety and efficacy of PRI-002 in patients with mild cognitive impairment (MCI) or mild dementia due to AD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
304
Neuro Health Centrum ltd.
Brno, Czechia
NeuropsychiatrieHK, s.r.o.
Hradec Králové, Czechia
A-Shine, s.r.o.
Pilsen, Czechia
CLINTRIAL, s.r.o.
Prague, Czechia
FORBELI s.r.o.
Prague, Czechia
Neuropsychiatrie s.r.o.
Prague, Czechia
To evaluate the safety and tolerability of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on incidence of drug-related adverse events (AEs).
Percentage of subjects with at least 1 drug- related AE or drug-related serious adverse event (SAE) between Baseline and Week 48.
Time frame: Baseline to week 48.
To evaluate the efficacy of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on the Clinical Dementia Rating - Sum of Boxes (CDR-SB).
Change from Baseline to Week 48 in global outcome as measured by CDR-SB.
Time frame: Baseline to week 48.
To evaluate safety and tolerability of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on AEs, amyloid related imaging abnormalities oedema (ARIA-E) and haemosiderin (ARIA-H), and treatment discontinuations due to AEs.
Percentage of subjects with AEs and SAEs from Baseline until End of Study (EoS).
Time frame: Through study completion up to 96 weeks.
To evaluate clinical outcome measures of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD.
Change from Baseline to Week 48 of: Alzheimer's disease cooperative study - activities of daily living inventory (ADCS-ADL), Alzheimer disease assessment scale - cognitive subscale, 13 tests (ADAS-Cog 13)
Time frame: Through study completion up to 48 weeks.
To evaluate clinical outcome measures of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD.
Change from Baseline to study completion of: CDR-SB, ADCS-ADL, ADAS-Cog 13
Time frame: Baseline to study completion.
To evaluate clinical outcome measures and biomarkers of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD.
Change from Baseline to EoT of: Mini mental state examination (MMSE) scores, Cerebrospinal fluid (CSF) concentrations of AD-related biomarkers including, but not limited to, ratio Aβ 1-42/1-40, p-tau, t-tau, Aβ oligomers, and tau oligomers, Plasma concentrations of AD-related biomarkers including, but not limited to, ratio Aβ 1-42/1-40, p-tau, t-tau, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and Aβ oligomers, Correlations between changes in CSF and plasma biomarkers and clinical changes (CDR-SB, ADCS-ADL, ADAS-Cog 13, MMSE)
Time frame: Baseline to study completion.
To follow drug levels of PRI-002 during multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD.
PRI-002 plasma concentrations over time.
Time frame: Through study completion up to 96 weeks.
To evaluate the correlation between PRI-002 exposure and efficacy and the correlation between PRI-002 exposure and safety in subjects with MCI or mild dementia due to AD.
Correlations between PRI-002 plasma concentrations and clinical changes (CDR-SB, ADCS-ADL, ADAS-Cog 13, MMSE) and safety endpoints (AEs and SAEs).
Time frame: Through study completion up to 96 weeks.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
INEP Medical s.r.o.
Prague, Czechia
Uniklinik RWTH Aachen
Aachen, Germany
Charité - Universitätsmedizin
Berlin, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, Germany
...and 28 more locations