Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (PRImus-AD)
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| ClinicalTrials.gov Identifier: NCT06182085 |
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Recruitment Status :
Recruiting
First Posted : December 26, 2023
Last Update Posted : May 9, 2024
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Sponsor:
PRInnovation GmbH
Collaborators:
Priavoid
Federal Agency for Disruptive Innovation - SPRIN-D
Julius Clinical
Information provided by (Responsible Party):
PRInnovation GmbH
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Mild Cognitive Impairment Due to Alzheimer's Disease Alzheimer's Disease, Early Onset | Drug: PRI-002 Drug: Placebo | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 270 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Randomised, Double-blind, Placebo-controlled Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (PRImus-AD) |
| Actual Study Start Date : | December 1, 2023 |
| Estimated Primary Completion Date : | April 30, 2026 |
| Estimated Study Completion Date : | April 30, 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Alzheimer disease
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo
Daily oral administration of 3 capsules in the morning and evening.
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Drug: Placebo
Oral administration |
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Experimental: PRI-002, dosage arm 1
Daily oral administration of 3 capsules in the morning and evening, lower dose.
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Drug: PRI-002
Oral administration
Other Name: Contraloid |
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Experimental: PRI-002, dosage arm 2
Daily oral administration of 3 capsules in the morning and evening, higher dose.
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Drug: PRI-002
Oral administration
Other Name: Contraloid |
Primary Outcome Measures :
- To evaluate the safety and tolerability of multiple doses of PRI-002 in subjects with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease (AD), based on incidence of drug-related adverse events (AEs). [ Time Frame: Baseline to week 48. ]Number of subjects in all treatment arms with at least 1 drug-related adverse event (AE) or drug-related serious adverse event (SAE) between baseline and 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). [ Time Frame: Baseline to week 48. ]Change of individual cognitive capablities of subjects in all treatment arms from baseline to week 48 as measured by Clinical Dementia Rating-Sum of Boxes (CDR-SB, minimum value = 0, maximum value = 18, higher values correlate with a worse outcome)).
Secondary Outcome Measures :
- To evaluate safety and tolerability of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on AEs recorded in all 3 treatment arms. [ Time Frame: Baseline to week 48. ]Percentage of subjects with AEs and SAEs from baseline until end of treatment.
- To evaluate safety and tolerability of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on amyloid related imaging abnormalities oedema (ARIA-E) and haemosiderin (ARIA-H). [ Time Frame: Baseline to week 48. ]Percentage of subjects with ARIA-E and ARIA-H from baseline until end of treatment.
- To evaluate safety and tolerability of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on treatment discontinuations due to AEs. [ Time Frame: Baseline to week 48. ]Percentage of subjects who stopped treatment due to AEs or SAEs from baseline until end of treatment.
- To evaluate clinical outcome measures in subjects with MCI or mild dementia due to AD based on psychometric testing. [ Time Frame: Baseline to week 48. ]Change in cognitive performance measured by Alzheimer's disease cooperative study - activities of daily living (ADCS-ADL, minimum value = 0, maximum value = 78, higher values correlate with a better outcome), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog 13, minimum value = 0, maximum value = 85, higher values correlate with a worse outcome), and mini mental state examination (MMSE, minimum value = 0, maximum value = 30, higher values correlate with a better outcome).
- To evaluate cerebrospinal fluid (CSF) biomarkers changes after mutiple doses of PRI-002 in subjects with MCI or mild dementia due to AD. [ Time Frame: Baseline to week 48. ]Change of cerebrospinal fluid (CSF) biomarker concentrations: ratio Aβ 1-42 [pg/ml] /1-40 [pg/ml], p-tau [pg/ml], t-tau [pg/ml], Aβ oligomers [fM], tau oligomers [fM].
- To evaluate plasma biomarker changes after multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD. [ Time Frame: Baseline to week 48. ]Change of plasma biomarker concentrations: ratio Aβ 1-42 [pg/ml] /1-40 [pg/ml], p-tau [pg/ml] , t-tau [pg/ml], neurofilament light chain (NfL) [pg/ml], glial fibrillary acidic protein (GFAP) [pg/ml], Aβ oligomers [fM], and tau oligomers [fM].
- To follow drug levels of PRI-002 during multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD. [ Time Frame: Baseline to week 48. ]Anaysis of PRI-002 plasma concentrations [ng/ml] over time.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 55 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Signed and dated written informed consent obtained from the subject and study companion in accordance with applicable regulations
- Male or female, aged 55 to 80 years, inclusive
- 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)
- Body mass index (BMI) between 18.5 and 30.0 kg/m2, inclusive, (weight in kilograms and height in meters will be combined to report BMI in kg/m2)
- Diagnosed with MCI due to AD or mild dementia due to AD, according to the NIA-AA criteria11
- MMSE score of 22 to 30 points on a scale, inclusive, the highest score achievable is 30
- Repeatable battery for the assessment of neuropsychological status - delayed memory index (RBANS-DMI) score ≤85 units on a scale
- CDR global score of 0.5 or 1 with a memory score ≥0.5 units on a scale
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Confirmation of AD diagnosis, by
- CSF biomarker profile reflecting AD, according to NIA-AA11, or
- existing positive amyloid positron emission tomography (PET) evidence
- Fluency in local language and evidence of adequate intellectual functioning in the opinion of the investigator
- 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:
- Unable to give informed consent in accordance with applicable regulations
- Diagnosed with moderate or severe dementia due to AD according to National Institute on Aging - Alzheimer's Association (NIA-AA)
- History or evidence of any other central nervous system (CNS) disorder(s) that could be interpreted as a cause of cognitive impairment or dementia
- History of known or suspected seizures, loss of consciousness, or significant head trauma within 2 years before Screening
- History of known or suspected stroke or transient ischaemic attack (TIA) within 2 years before Screening
- Evidence of other clinically significant lesions on brain MRI (Fazekas score 312)
- History or presence of clinically evident cerebrovascular disease (diagnosis of possible, probable, or definite vascular dementia)
- Other significant pathological findings on brain MRI (for example more than 10 microhaemorrhages or a single macrohaemorrhage >10 mm at the greatest diameter)
- Unstable medical, neurological, or psychiatric condition, or presence of major depressive episode at Screening
- Life-time history of schizophrenia or history of uncontrolled bipolar disorder within 5 years before Screening
- Having a bleeding disorder that is not under adequate control (defined as a platelet count <50 000 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).
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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.
- 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.
- Known to be human immunodeficiency virus (HIV) positive
- Known to be hepatitis C or chronic hepatitis B positive
- 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
- 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)
- Use of anti-Aβ monoclonal antibody therapy at Baseline
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Treatment with one of the following substances:
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Typical antipsychotic or neuroleptic medication within 90 days before Screening (except for
≤1 mg risperidon, and ≤300 mg quetiapin).
- Chronic use of opiates or opioids (including long-acting opioid medication) within 90 days before Screening
- Stimulant medications (amphetamine, methylphenidate preparations, or modafinil) within 30 days before Screening
- Chronic use of benzodiazepines, barbiturates, or hypnotics within 90 days before Screening
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- Contraindication to MRI. Patients with MRI compatible pacemakers may be allowed to enter the study.
- Prior or current participation in a clinical trial testing active immunisation against Aβ or tau.
- 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06182085
Contacts
| Contact: Alexander Brener, Dr. | 004915150329843 | info@prinnovation.org | |
| Contact: Kathrin Thiem, Dr. | 004915150329843 | info@prinnovation.org |
Locations
Show 38 study locations
Sponsors and Collaborators
PRInnovation GmbH
Priavoid
Federal Agency for Disruptive Innovation - SPRIN-D
Julius Clinical
Investigators
| Study Chair: | Gerhard Tischler, Dr. | PRInnovation |
| Responsible Party: | PRInnovation GmbH |
| ClinicalTrials.gov Identifier: | NCT06182085 |
| Other Study ID Numbers: |
PRI-002-004 |
| First Posted: | December 26, 2023 Key Record Dates |
| Last Update Posted: | May 9, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by PRInnovation GmbH:
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PRI-002 PRImus-AD Clinical Dementia Rating Sum of Boxes (CDR-SB) Prodromal Alzheimer's disease Mild Alzheimer's disease dementia |
Additional relevant MeSH terms:
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Alzheimer Disease Dementia Cognitive Dysfunction Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders Cognition Disorders |