Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD)

NCT ID: NCT06182085

Last Updated: 2025-12-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 304 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2026-04-30

Brief Summary

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.

Detailed Description

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.

Conditions

Mild Cognitive Impairment Due to Alzheimer's Disease; Alzheimer's Disease, Early Onset

Keywords

PRI-002; PRImus-AD; Clinical Dementia Rating Sum of Boxes (CDR-SB); Prodromal Alzheimer's disease; Mild Alzheimer's disease dementia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Daily oral administration of 3 capsules in the morning and evening.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral administration

PRI-002, dosage arm 1

Daily oral administration of 3 capsules in the morning and evening, lower dose.

Group Type: EXPERIMENTAL

PRI-002

Intervention Type: DRUG

Oral administration

PRI-002, dosage arm 2

Daily oral administration of 3 capsules in the morning and evening, higher dose.

Group Type: EXPERIMENTAL

PRI-002

Intervention Type: DRUG

Oral administration

Interventions

PRI-002

Oral administration

Intervention Type: DRUG

Placebo

Oral administration

Intervention Type: DRUG

Other Intervention Names

Contraloid

Eligibility Criteria

Inclusion Criteria

1. Signed and dated written informed consent obtained from the subject and study companion in accordance with applicable regulations.

2. Male or female, aged 55 to 80 years, inclusive.

3. For female subjects: not being of child-bearing potential. This is defined as either permanently sterilised (via hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal (defined as no menses for 12 months without an alternative medical cause).

For male subjects who are sexually active with women of child-bearing potential: agreeing to use acceptable contraception (using a condom or having demonstrated successful vasectomy) and not donate sperm from Screening until 12 weeks after the last dose of study treatment.

4. Body mass index (BMI) between 18.5 and 30.0 kg/m2, inclusive.

5. Diagnosed with MCI due to AD or mild dementia due to AD, according to the NIA-AA criteria.

6. MMSE score of 22 to 30, inclusive.

7. Repeatable battery for the assessment of neuropsychological status - delayed memory index (RBANS-DMI) score ≤85.

8. CDR global score of 0.5 or 1 with a memory score ≥0.5.

9. Confirmation of AD diagnosis, by

• CSF biomarker profile reflecting AD, according to NIA-AA, or
• existing positive amyloid positron emission tomography (PET) evidence.

10. Fluency in local language and evidence of adequate intellectual functioning in the opinion of the investigator.

11. Having a reliable informant or caregiver who is willing and able to act as the study companion throughout the duration of the subject's participation. The subject and the study companion must have frequent interaction (defined as a minimum of 6 hours/week on average) according to subject's report.

Exclusion Criteria

1. Unable to give informed consent in accordance with applicable regulations.

2. Diagnosed with moderate or severe dementia due to AD according to NIA-AA.

3. History or evidence of any other central nervous system (CNS) disorder(s) that could be interpreted as a cause of cognitive impairment or dementia.

4. History of known or suspected seizures, loss of consciousness, or significant head trauma within 2 years before Screening.

5. History of known or suspected stroke or transient ischaemic attack (TIA) within 2 years before Screening.

6. Evidence of other clinically significant lesions on brain MRI (Fazekas score 3).

7. History or presence of clinically evident cerebrovascular disease (diagnosis of possible, probable, or definite vascular dementia).

8. Other significant pathological findings on brain MRI (for example more than 10 microhaemorrhages or a single macrohaemorrhage >10 mm at the greatest diameter).

9. Unstable medical, neurological, or psychiatric condition, or presence of major depressive episode at Screening.

10. Life-time history of schizophrenia or history of uncontrolled bipolar disorder within 5 years before Screening.

11. Having a bleeding disorder that is not under adequate control (defined as a platelet count <50000 or international normalised ratio [INR] >1.5). Participants who are on anticoagulant therapy (for example, warfarin), should have their anticoagulant status optimised and be on a stable dose for 30 days before Screening. Anticoagulant therapy (e.g., clopidogrel bisulfate, carbasalate calcium 100 mg/day, or aspirin 325 mg/day or less) is permitted provided this therapy does not represent a contraindication for a lumbar puncture and CSF sampling (if CSF sampling is required in the absence of historical PET evidence).

12. Having significant kidney disease as indicated by either of the following:

• Creatinine clearance (eGFR) ≤30 mL/min/1.73m2) as estimated using the modification of diet in renal disease (MDRD) method, or
• Creatinine ≥2 mg/dL.

13. Having impaired hepatic function as indicated by aspartate amino transferase (AST) or alanine amino transferase (ALT) >3-fold the upper limit of normal (ULN), or total bilirubin >2-fold ULN, at Screening.

14. Known to be human immunodeficiency virus (HIV) positive.

15. Known to be hepatitis C or chronic hepatitis B positive.

16. Having any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, MRI, or ECG at Screening or Baseline which in the opinion of the investigator requires further investigation or treatment or which may interfere with study procedures or safety.

17. Use of licensed symptomatic AD medication for less than 90 days or at a non-stable dose over the past 90 days at Baseline (for example acetylcholinesterase inhibitors, memantine, ginkgo).

18. Use of anti-Aβ monoclonal antibody therapy at Baseline.

19. Treatment with one of the following substances:

1. Typical antipsychotic or neuroleptic medication within 90 days before Screening (except for

≤1 mg risperidon, and ≤300 mg quetiapin).

2. Chronic use of opiates or opioids (including long-acting opioid medication) within 90 days before Screening.

3. Stimulant medications (amphetamine, methylphenidate preparations, or modafinil) within 30 days before Screening.

4. Chronic use of benzodiazepines, barbiturates, or hypnotics within 90 days before Screening.

20. Contraindication to MRI. Patients with MRI compatible pacemakers may be allowed to enter the study.

21. Prior or current participation in a clinical trial testing active immunisation against Aβ or tau.

22. Participation in a clinical trial and having taken at least 1 dose of the investigational medicinal product (IMP), within 5 times the IMP half-life time before Baseline, unless confirmed as having been on placebo.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Priavoid

UNKNOWN

Sponsor Role: collaborator

Federal Agency for Disruptive Innovation - SPRIN-D

UNKNOWN

Sponsor Role: collaborator

Julius Clinical

INDUSTRY

Sponsor Role: collaborator

PRInnovation GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gerhard Tischler, Dr.

Role: STUDY_CHAIR

PRInnovation

Locations

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

INEP Medical s.r.o.

Prague, , Czechia

Uniklinik RWTH Aachen

Aachen, , Germany

Charité - Universitätsmedizin

Berlin, , Germany

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Universitätsklinikum Magdeburg

Magdeburg, , Germany

ISPG - Institut für Studien zur Psychischen Gesundheit

Mannheim, , Germany

Technische Universität München

München, , Germany

Universitätsklinikum Münster - Klinik für Allgemeine Neurologie

Münster, , Germany

University Medical Center Rostock

Rostock, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Ospedale Bellaria - IRCCS Istituto delle Scienze Neurologiche

Bologna, , Italy

ASST Spedali Civili di Brescia

Brescia, , Italy

Clinica Neurologica Dipartimento di Neuroscienze e Imaging (CAST)

Chieti, , Italy

IRCCS Ospedale San Raffaele

Milan, , Italy

Fondazione IRCCS.Istituto Neurologico Carlo Besta

Milan, , Italy

Ospedale Santa Maria della Misericordia

Perugia, , Italy

AOU Policlinico Umberto I

Rome, , Italy

Fondazione Policlinico Universitario A. Gemelli IRCCS

Rome, , Italy

Brain Research Center Den Bosch B.V.

's-Hertogenbosch, , Netherlands

Brain Research Center Amsterdam B.V.

Amsterdam, , Netherlands

Brain Research Center Zwolle B.V.

Zwolle, , Netherlands

Revit Sp. z o.o., Podlaskie Centrum Psychogeriatrii

Bialystok, , Poland

Krakowska Akademia Neurologii Sp. z o.o., Centrum Neurologii Klinicznej

Krakow, , Poland

NeuroCor, ul. Medweciego 7/U12

Krakow, , Poland

Euromedis Sp. z o.o., Centrum Medyczne EUROMEDIS

Szczecin, , Poland

Neuroprotect Sp. z o.o., Centrum Medyczne NeuroProtect

Warsaw, , Poland

Wielospecjalistyczne Centrum Medyczne "Ibismed" s.c.

Zabrze, , Poland

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Fundació ACE - Institut Català de Neurociències Aplicades

Barcelona, , Spain

Hospital Universitario Virgen Macarena,

Seville, , Spain

Hospital Universitario Doctor Peset

Valencia, , Spain

Hospital Viamed Montecanal

Zaragoza, , Spain

Countries

France; Czechia; Germany; Italy; Netherlands; Poland; Spain

References

Jurgens D, Tischler G, Brener A, Bartsch T, Kauselmann G, Adermann K, Zeiger K, Lindner K, Gabelich JA, Willbold D, Peters O. Drug Development. Alzheimers Dement. 2025 Dec;21 Suppl 5(Suppl 5):e103102. doi: 10.1002/alz70859_103102.

Reference Type: DERIVED

PMID: 41449684 (View on PubMed)

Other Identifiers

PRI-002-004

Identifier Type: -

Identifier Source: org_study_id