Overview
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PRI_002__PRImus_AD__Phase_2_Tr["PRI-002 PRImus-AD Phase 2 Trial"]
PRI_002__PRImus_AD__Phase_2_Tr["PRImus-AD"]
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PRImus-AD (NCT06182085) is a Phase 2 randomized, double-blind, placebo-controlled trial evaluating PRI-002 (also known as Contraloid), a novel all-D-amino acid peptide, in patients with mild cognitive impairment (MCI) due to Alzheimer's disease or mild dementia due to AD["@pri0022023"].
PRI-002 represents a unique therapeutic approach that aims to directly disassemble toxic amyloid-beta (Abeta) oligomers into non-toxic monomer units, differentiating it from other amyloid-targeting therapies that focus on increasing degradation rates of different Abeta species["@prinusad"].
Trial Details
...Overview
Mermaid diagram (expand to render)
PRImus-AD (NCT06182085) is a Phase 2 randomized, double-blind, placebo-controlled trial evaluating PRI-002 (also known as Contraloid), a novel all-D-amino acid peptide, in patients with mild cognitive impairment (MCI) due to Alzheimer's disease or mild dementia due to AD["@pri0022023"].
PRI-002 represents a unique therapeutic approach that aims to directly disassemble toxic amyloid-beta (Abeta) oligomers into non-toxic monomer units, differentiating it from other amyloid-targeting therapies that focus on increasing degradation rates of different Abeta species["@prinusad"].
Trial Details
| Parameter | Value |
|-----------|-------|
| NCT Number | NCT06182085 |
| Phase | Phase 2 |
| Status | Active, not recruiting |
| Sponsor | PRInnovation GmbH |
| Collaborators | Priavoid, Federal Agency for Disruptive Innovation - SPRIN-D, Julius Clinical |
| Enrollment | 304 patients |
| Duration | 48 weeks (primary), up to 96 weeks (study completion) |
| Location | Czechia, Germany, Italy, Netherlands, Poland, Spain |
| Drug | PRI-002 (Contraloid) |
| Dosage | Daily oral administration, 3 capsules in morning and evening |
| Acronym | PRImus-AD |
Mechanism of Action
PRI-002 is an all-D-amino acid peptide (all-D-peptide) with a rationally designed primary structure that specifically targets and removes Aβ oligomers. Unlike other amyloid-targeting approaches in development, PRI-002 operates through a unique disassembly mechanism:
Unique Therapeutic Principle
Target: Neurotoxic Aβ oligomers (prion-like behaving species)
Mechanism: Disassembles toxic oligomers into non-toxic Aβ monomer units
Approach: Direct oligomer elimination rather than enhancing degradationThis mechanism differs fundamentally from:
- Anti-amyloid antibodies that enhance clearance
- BACE inhibitors that reduce Aβ production
- Immunotherapies that target plaque formation
Rationale
Research suggests that Aβ oligomers are the most toxic species in Alzheimer's disease pathology, rather than monomers or fibrils. By specifically targeting and disassembling these oligomers, PRI-002 aims to reduce the neurotoxic effects that drive cognitive decline in AD.
Patient Population
Inclusion Criteria
- Age: 55-80 years
- Diagnosis: MCI due to AD or mild dementia due to AD (NIA-AA criteria)
- MMSE score: 22-30
- CDR global score: 0.5 or 1 with memory score ≥0.5
- RBANS-DMI score: ≤85
- AD confirmation: CSF biomarker profile (AD signature) or positive amyloid PET
- Companion requirement: Subject must have reliable informant/caregiver
Exclusion Criteria
- Moderate or severe dementia due to AD
- Other CNS disorders causing cognitive impairment
- History of stroke, TIA, or significant head trauma within 2 years
- Evidence of cerebrovascular disease
- Unstable medical, neurological, or psychiatric conditions
- Major depressive episode at screening
- Use of anti-Aβ monoclonal antibody therapy at baseline
- Prior participation in Aβ or tau active immunization trials
Study Design
Arms
| Arm | Type | Description |
|-----|------|-------------|
| Placebo | Placebo Comparator | Daily oral administration of 3 capsules morning and evening |
| PRI-002, dosage arm 1 | Experimental | Lower dose, daily oral |
| PRI-002, dosage arm 2 | Experimental | Higher dose, daily oral |
Randomization
- Allocation: Randomized
- Intervention Model: Parallel
- Masking: Quadruple (participant, care provider, investigator, outcomes assessor)
Endpoints
Primary Endpoints
Safety and Tolerability
- Measure: Incidence of drug-related adverse events (AEs) and serious adverse events (SAEs)
- Timeframe: Baseline to Week 48
Efficacy
- Measure: Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB)
- Timeframe: Baseline to Week 48
Secondary Endpoints
| Endpoint | Timeframe |
|----------|-----------|
| Safety: AEs, ARIA-E, ARIA-H, treatment discontinuations | Through week 96 |
| ADCS-ADL and ADAS-Cog 13 changes | Baseline to week 48 |
| CDR-SB, ADCS-ADL, ADAS-Cog 13 | Baseline to study completion |
| MMSE scores | Baseline to End of Treatment (EoT) |
| CSF biomarkers: Aβ 1-42/1-40 ratio, p-tau, t-tau, Aβ oligomers, tau oligomers | Baseline to EoT |
| Plasma biomarkers: Aβ 1-42/1-40 ratio, p-tau, t-tau, NfL, GFAP, Aβ oligomers | Baseline to EoT |
| PRI-002 plasma concentrations (PK) | Through week 96 |
| Exposure-efficacy and exposure-safety correlations | Through week 96 |
Study Locations
Czechia
- Neuro Health Centrum ltd., Brno
- NeuropsychiatrieHK, s.r.o., Hradec Králové
- A-Shine, s.r.o., Pilsen
- CLINTRIAL, s.r.o., Prague
- FORBELI s.r.o., Prague
- Neuropsychiatrie s.r.o., Prague
- INEP Medical s.r.o., Prague
Germany
- Uniklinik RWTH Aachen, Aachen
- Charité - Universitätsmedizin, Berlin
- Universitätsklinikum Düsseldorf, Düsseldorf
- Universitätsklinikum Magdeburg, Magdeburg
- ISPG - Institut für Studien zur Psychische Gesundheit, Mannheim
- Technische Universität München, München
- Universitätsklinikum Münster, Münster
- University Medical Center Rostock, Rostock
- Universitätsklinikum Ulm, Ulm
Italy
- Ospedale Bellaria - IRCCS Istituto delle Scienze Neurologiche, Bologna
- ASST Spedali Civili di Brescia, Brescia
- Clinica Neurologica Dipartimento di Neuroscienze e Imaging (CAST), Chieti
- IRCCS Ospedale San Raffaele, Milan
- Fondazione IRCCS.Istituto Neurologico Carlo Besta, Milan
- Ospedale Santa Maria della Misericordia, Perugia
- AOU Policlinico Umberto I, Rome
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome
Netherlands
- Brain Research Center Den Bosch B.V., 's-Hertogenbosch
- Brain Research Center Amsterdam B.V., Amsterdam
- Brain Research Center Zwolle B.V., Zwolle
Poland
- Revit Sp. z o.o., Podlaskie Centrum Psychogeriatrii, Bialystok
- Krakowska Akademia Neurologii Sp. z o.o., Krakow
- NeuroCor, Krakow
- Euromedis Sp. z o.o., Szczecin
- NeuroProtect Sp. z o.o., Warsaw
- Wielospecjalistyczne Centrum Medyczne "Ibismed" s.c., Zabrze
Spain
- Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar
- Fundació ACE - Institut Català de Neurociències Aplicades, Barcelona
- Hospital Universitario Virgen Macarena, Seville
- Hospital Universitario Doctor Peset, Valencia
- Hospital Viamed Montecanal, Zaragoza
Clinical Significance
Novel Mechanism
PRI-002 represents a fundamentally different approach to amyloid-targeting therapy:
- Direct Disassembly: Unlike antibodies that rely on Fc-mediated clearance, PRI-002 actively disassembles toxic oligomers
- All-D-Peptide: The use of all D-amino acids provides enhanced stability and potential for oral administration
- Oligomer-Specific: Targets the most toxic Aβ species directly
Implications for AD Treatment
If successful, PRI-002 could provide:
- An oral treatment option for early AD
- Complementary mechanism to monoclonal antibody therapies
- Potential for combination approaches
- [Amyloid Cascade Hypothesis](/mechanisms/amyloid-cascade-hypothesis)
- [Amyloid-beta](/proteins/amyloid-beta)
- [Amyloid-beta Oligomers](/proteins/amyloid-beta-oligomers)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Mild Cognitive Impairment](/diseases/mci)
- [Lecanemab CLARITY-AD Trial](/clinical-trials/lecanemab-clarity-ad)
- [Donanemab TRAILBLAZER-ALZ](/clinical-trials/donanemab-trailblazer-alz2)
- [BAN2401 Phase 2b Trial](/clinical-trials/ban2401-201)
- [A4 Study](/clinical-trials/a4-study)
References
[PRInnovation GmbH. Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (2023)](https://clinicaltrials.gov/study/NCT06182085)
[ClinicalTrials.gov: NCT06182085](https://clinicaltrials.gov/study/NCT06182085)