A comparison study of TRx0237 (LMTM) and placebo in patients with Alzheimer's Disease.

Phase 1

Active, not recruiting

• Conditions: Alzheimer’s Disease; MedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2017-003558-17-GB
• Lead Sponsor: TauRx Therapeutics Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-11-09
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

To be eligible for enrollment in this study, a subject must meet all of the following inclusion criteria:

1. AD, encompassing probable AD and MCI-AD based on 2011 NIA/AA criteria:
• All cause dementia and probable AD (probable AD)
In brief, subjects with probable AD dementia must have insidious onset, worsening impairment in at least two cognitive areas (learning and recall, language, executive function, visuospatial skills), sufficient to significantly interfere with work or usual activities, that is not explained by delirium, drugs, major psychiatric disorder, medical illness, cerebrovascular disease, other forms of dementia, or neurological disorder. The accuracy of the diagnosis will be confirmed independently by the diagnosing physician at site.
OR
• MCI-AD
In subjects with MCI-AD, there should be evidence of concern about a change in cognition, in comparison with the person’s previous level verified by a knowledgeable informant or clinician. Other mild cognitive deficits may also be present, but there must be preservation of independence in functional abilities. Subjects should not meet the criteria for dementia. The cognitive changes must be mild and there must be no evidence of a significant impairment in social or occupational functioning. Impairments must not be explained by delirium, drugs, major psychiatric disorder, medical illness, cerebrovascular disease, other forms of dementia, or neurological disorder.
of dementia, or neurological disorder.
2. Documented PET scan that is positive for amyloid; if most recent PET scan was performed >3 years prior to Screening and was negative, it may be repeated (a negative amyloid PET scan within the 3 years prior to Screening is exclusionary)
3. MMSE score of 16-27 (inclusive) at Screening, subject to stratification requirements
4. Global CDR score of 0.5 to 2 at Screening (if 0.5, including a score of >0 in one of the functional domains: Community Affairs, Home and Hobbies, or Personal Care)
5. Age <90 years at Screening
6. Females must meet one of the following:
• Surgically sterile (hysterectomy, bilateral salpingectomy / oophorectomy) for at least 6 months minimum
• Have undergone bilateral tubal occlusion / ligation at least 6 months prior
• Post-menopausal for at least 1 year
• Using adequate contraception (a barrier method [such as condom, diaphragm or cervical/vault cap] with spermicidal foam, gel, film, cream, or suppository; intrauterine device [IUD] or system, or oral or long-acting injected or implanted hormonal contraceptives for at least 90 days prior to Baseline; or vasectomized partner [with the appropriate post-vasectomy documentation of the absence of spermatozoa in the ejaculate]) or true abstinence (when this is in line with the preferred and usual lifestyle of the subject); subjects must be competent to use adequate contraception and to agree to continue to maintain adequate contraception throughout participation in the study (including up to 4 weeks after the last dose of study drug)
7. Subject and/or, in the case of reduced decision-making capacity, legally acceptable representative(s) (LAR(s)), consistent with local and national law, is able to read, understand, and provide written informed consent in the designated language of the study site
8. Has one (or more) identified adult study partner (i.e., a caregiver or informant) who meets the following criteria:
• Either lives with the subject, or in the investigator’s opinion, the extent of contact is sufficien

Exclusion Criteria

1. Significant central nervous system disorder other than probable AD or MCI-AD
2. Significant intracranial focal or vascular pathology seen on brain MRI scan that would, based on the independent reviewer imaging evaluation, lead to a diagnosis other than probable AD or MCI-AD, including but not limited to:
• Large confluent white matter hyperintense lesions
• Other focal brain lesions judged clinically relevant by the investigator
• Evidence of a prior or current macrohemorrhage
3. Clinical evidence or history of any of the following :
• Cerebrovascular accident
• Transient ischemic attack
• Significant head injury, for example, associated loss of consciousness, skull fracture or persisting cognitive impairment
• Other unexplained or recurrent loss of consciousness =15 minutes
4. Diagnosed with epilepsy
5. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria met:
• Major depressive disorder
• Schizophrenia
• Other psychotic disorders, bipolar disorder
• Substance (including alcohol) related disorders
6. Metal implants in the head, pacemaker, cochlear implants, or any other non-removable items that are contraindications to MRI.
7. Resides in hospital or moderate to high dependency continuous care
8. Any physical disability that would prevent completion of study procedures or assessments
9. History of swallowing difficulties
10. Pregnant or breastfeeding
11. G6PD deficiency based on World Health Organization classification
12. History of significant hematological abnormality or current acute or chronic clinically significant abnormality, including:
• History of hemoglobinopathy, myelodysplastic syndrome, hemolytic anemia, or splenectomy
• Screening Hgb value below age/sex appropriate lower limit of the central laboratory normal range
13. Abnormal serum chemistry laboratory value at Screening deemed to be clinically significant by the investigator. In addition, subjects with either of the following abnormalities must be excluded:
• Creatinine clearance <30 mL/min
• TSH above laboratory normal range
14. Clinically significant cardiovascular disease or abnormal assessments such as:
• Hospitalization for acute coronary syndrome or symptoms consistent with angina pectoris, within the 12 months preceding Baseline
• Signs or symptoms of clinical heart failure within the 12 months preceding Baseline
• Atrial fibrillation on Screening ECG or history of atrial fibrillation that is not currently controlled
• QTcF at Screening >460 msec in males or >470 msec in females, or low or flat T waves making measurement of QT interval unreliable
• Recent history of poorly controlled hypertension, systolic blood pressure >180 mmHg, or diastolic blood pressure >100 mmHg
• Hypotension: systolic blood pressure <100 mmHg
• Heart rate <48 bpm or >96 bpm by measurement of vital signs or by local ECG at Screening
15. Pre-existing or current signs or symptoms of respiratory failure,
• Subjects with currently diagnosed moderate to severe sleep apnea should be excluded; the definition of moderate to severe includes oxygen supplementation
16.Concurrent acute or chronic clinically significant immunologic, hepatobiliary, or endocrine disease, and/or other unstable or major disease other than probable AD or MCI-AD; the following are specifically excluded:
• Active hepatitis or primary biliary cirrhosis
• Active Human T-Cell Lymphocytic Virus Type III, Lymphadenopathy Associated Virus, any mutants or derivatives of HLTV-III or

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified