Phase 2 PRIMUS-AD Trial to Test Anti-Amyloid Oligomer PRI-002 in Alzheimer Disease

Dagmar Jürgens, PhD

Details behind a new phase 2 proof-of-concept study, dubbed PRIMUS-AD (NCT06182085), testing investigational PRI-002 (PRInnovation), an oral small-molecule anti-amyloid-ß (Aß) oligomer disaggregator, were unveiled at the 2025 Alzheimer’s Association International Conference (AAIC), held July 27-31, in Toronto, Canada. The double-blind, placebo-controlled trial includes around 300 patients with mild cognitive impairment (MCI) and mild dementia caused by Alzheimer disease (AD), with data expected in mid-2026.¹

Spanning across 40 study sites in Europe, PRIMUS-AD tests the therapeutic efficacy and safety of 2 doses of PRI-002 (300 mg, 600 mg), an all-D-enantiomeric peptide, against placebo. The study employs an adaptive design for 48 to 96 weeks of treatment duration, using change in Clinical Dementia Rating-Sum of Boxes score at week 48 as the primary efficacy outcome. In the trial, a follow-up assessment is planned 12 weeks after the end of treatment.

Lead investigator Dagmar Jürgens, PhD, director of Clinical Development at Priavoid, and colleagues recorded a screening failure rate of 42% from the 540 original patients screened. The study will primarily assess the safety of PRI-002, which is not expected to induce amyloid-related imaging abnormalities (ARIA), according to study authors. During the first 24 weeks of the study, investigators will closely monitor for ARIA in the initial 90 patients enrolled.

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Eligible participants for this study include males and females aged 55 to 80 years with a body mass index between 18.5 and 30.0 kg/m², who have been diagnosed with MCI or mild dementia due to AD based on NIA-AA criteria. Participants must have Mini-Mental State Exam (MMSE) scores between 22–30, RBANS-DMI scores of 85 or less, and a CDR global score of 0.5 or 1. Confirmation of AD must be supported by either CSF biomarkers or prior positive amyloid PET imaging. Fluency in the local language, adequate cognitive function, and the presence of a reliable caregiver are also required.²

Individuals with moderate or severe AD, other neurological or psychiatric conditions, recent seizures, strokes, or MRI abnormalities are excluded. Additional exclusions include unstable medical conditions, significant hepatic or renal impairment, bleeding disorders, or infections such as HIV or hepatitis B/C. Patients must not have used certain medications or participated in trials involving active immunization against Aβ or tau. Use of anti-Aβ monoclonal antibodies or recent changes in AD medications are also disqualifying factors.

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.³

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.

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REFERENCES
1. Jürgens D, Tischler G, Brener A, et al. 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: AAIC 2025; July 27-31; Toronto, Canada. ABSTRACT 103102.
2. Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (PRImus-AD). Clinicaltrials.gov. Updated May 28, 2025. Accessed July 31, 2025. https://clinicaltrials.gov/study/NCT06182085?intr=PRI-002&rank=1
3. 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