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About
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.
Full 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.
Enrollment
Sex
Ages
Volunteers
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
Confirmation of AD diagnosis, by
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).
Having significant kidney disease as indicated by either of the following:
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
Treatment with one of the following substances:
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
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.
Primary purpose
Allocation
Interventional model
Masking
270 participants in 3 patient groups, including a placebo group
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Central trial contact
Alexander Brener, Dr.; Kathrin Thiem, Dr.
Data sourced from clinicaltrials.gov
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