Alzheimer Trial PRImus-AD Tests Orally Available PRI-002 as New Treatment

In the clinical trial world, PRImus-AD is an ongoing phase 2a randomized, double-blind, placebo-controlled study (2022-503148-41) evaluating the safety and efficacy of PRI-002 (PRInnovation), a novel oral therapy targeting toxic amyloid-beta oligomers, in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD).¹

Presented at the 18th Clinical Trials on Alzheimer’s Disease Conference (CTAD), held December 1-4, in San Diego, California, the trial is currently underway at 40 study cites across 6 European countries: The Netherlands, Poland, Germany, Spain, Italy, and Czech Republic. In total, 540 patients were screened with 304 enrolled over the course of 12 months, with the first patient in (FPI) occurring in February 2024. The last patient out (LPO) is expected in June 2026 and results are anticipated in October of the same year.

Led by Dieter Willbold, PhD, director of the Institute for Physical Biology at Heinrich Heine University in Germany, the study assigns participants into one of three treatment arms: 300 mg PRI-002, 600 mg PRI-002, or placebo, with follow-up assessments conducted after treatment completion. The trial uses an adaptive design, with patients receiving treatment between 48 and 96 weeks.

The primary efficacy endpoint of the study is the Clinical Dementia Rating-Sum of Boxes (CDR-SB) and the primary safety endpoint is the incidence of drug-related adverse events (AEs). Secondary endpoints of the study include measuring AEs, ARIA-E, and ARIA-H, participant discontinuation, clinical outcomes, and evaluating the biomarkers and pharmacokinetics of PRI-002.

Inclusion criteria for the study include patients with MCI or mild dementia due to AD, cerebrospinal fluid (CSF) biomarker profile according to the National Institute on Aging–Alzheimer’s Association (NIA-AA) criteria or positive amyloid-PET, a Mini-Mental State Examination (MMSE) score 22 to 30 inclusive, a Repeatable Battery for the Assessment of Neuropsychological Status – Delayed Memory Index (RBANS-DMI) score of less than 85, and a Clinical Dementia Rating (CDR) global score 0.5 or 1 with a memory score of at least 0.5. Main exclusion criteria include history or evidence of any other central nervous system (CNS) disorder that could be interpreted as a cause of cognitive impairment or dementia.

READ MORE: Phase 2 PRImus-AD Trial to Test Anti-Amyloid Oligomer PRI-002 in Alzheimer Disease

PRI-002 is a synthetic peptide containing 12D-configurated amino acid residues provided in size 0 capsules for oral administration.¹ Unlike monoclonal antibodies that clear Aß plaques, PRI-002 is designed to directly target and destabilize toxic Aß oligomers, which are believed to play a central role in neuronal damage and cognitive decline in AD. Prior to PRImus-AD, the agent was tested in several preclinical proof-of-concept studies and a phase 1 single- (SAD) and multiple-ascending (MAD) trial.²

Published in Alzheimer’s & Dementia in 2020, the SAD (EUDRA-CT: 2017-000396-93; n = 40) tested doses of 4, 12, 36, 108, and 320 mg of PRI-002 vs placebo while the MAD (2018-002500-14; n = 24) tested 160 mg PRI-002 for 14 days or 320 mg for 28 days. All told, PRI-002 was considered safe and well tolerated in both cohorts, with rapid drug exposure that increased proportional to dose. Overall, plasma levels seen in tested humans after a single oral dose were in the same range as those observed in the highest dosed transgenic mice in successful proof-of-concept studies.

REFERENCES
1. Willbold D, Jürgens D, Tischler G, et al. The PRImus-AD study: design of the phase 2 study treating patients with MCI or mild dementia due to Alzheimer’s disease (AD) with the orally available PRI-002. Presented at Clinical Trials on Alzheimer’s Disease Conference (CTAD); December 1-4; San Diego, California
2. Kutzsche J, Jürgens D, Willuweit A, et al. Safety and pharmacokinetics of the orally available antiprionic compound PRI-002: a single and multiple ascending dose phase I study. Alzheimers Dement. 2020;6(1):e12001. doi:10.1002/trc2.12001