Alzheimer’s Disease MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Sponsors
TauRx Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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 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 L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare the LMTM dose of 16 mg/day with the placebo group on the following co-primary endpoints: a. ADAS-cog11 b. ADCS-ADL23 2. To assess the safety and tolerability of LMTM 16 mg/day given for up to 52 weeks;Secondary Objective: 1. To compare the LMTM dose of 16 mg/day with the placebo group in annualized rate of whole brain atrophy over 52 weeks as measured by brain MRI and quantified using the BSI 2. To compare the LMTM dose of 16 mg/day with the placebo group in temporal lobe 18F-FDG-PET change in SUVR (normalized to pons) over 52 weeks, restricted to subjects with CDR 0.5 at Screening 3. To compare the LMTM dose of 8 mg/day with the placebo group in temporal lobe 18F-FDG-PET change in SUVR (normalized to pons) over 52 weeks, restricted to subjects with CDR 0.5 at Screening 4. To compare the LMTM dose of 16 mg/day with the placebo group in temporal lobe 18F FDG-PET change in SUVR (normalized to pons) over 52 weeks, restricted to subjects with CDR 0.5 at Screening 5. To compare the LMTM dose of 8 mg/day with the placebo group in temporal lobe 18F-FDG-PET change in SUVR (normalized to pons) over 52 weeks, restricted to subjects with CDR 0.5 at Screening For more information please refer to protocol ;Primary end point(s): Primary Efficacy Endpoints for Double-Blind Treatment Period • ADAS-cog11 (LMTM 16 mg/day versus placebo) • ADCS-ADL23 (LMTM 16 mg/day versus placebo) ;Timepoint(s) of evaluation of this end point: Through the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints for Double-Blind Treatment Period • Annualized rate of whole brain atrophy on brain MRI using BSI (LMTM 16 mg/day versus placebo) • Difference in temporal lobe 18F-FDG-PET change in SUVR normalized to pons in subjects with CDR 0.5 at Screening (LMTM 16 mg/day versus placebo, and LMTM 8 mg/day versus placebo) • ADAS-cog11 and ADCS-ADL23 (LMTM 8 mg/day versus placebo) • Annualized rate of temporal and parietal lobe atrophy on brain MRI using BSI (LMTM 16 mg/day versus placebo, and LMTM 8 mg/day versus placebo) Secondary Endpoint for Open-Label, Delayed-Start Phase • Difference in disease progression on the co-primary clinical endpoints and the MRI imaging endpoint for subjects who started treatment in the double-blind treatment phase and those who started treatment in the open-label, delayed-start phase (referred to as "early" and "late" LMTM starters, respectively) • Only ADAS-cog11 will serve as a secondary endpoint; ADCS-ADL23 and other imaging endpoints are exploratory with the aim to be directionally supportive For exploratory endpoints, please refer to protocol.;Timepoint(s) of evaluation of this end point: Throughout the trial: | — |
Countries
Belgium, Canada, France, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactInformation Desk
TauRx Therapeutics Ltd
Outcome results
None listed