Mild to Moderate Alzheimer's Disease
Conditions
Brief summary
The purpose of this study is to determine the safety of 2 doses of LM11A-31-BHS in 180 patients with Alzheimer's Disease versus placebo and to access biomarker and clinical exploratory endpoints of LM11A-31-BHS
Detailed description
The goal of this AD Pilot is to conduct a prospective, double-blind, multicenter, phase IIa exploratory safety, feasibility and proof-of-concept trial in mild to moderate Alzheimer's disease patients with the orally bioavailable p75 neurotrophin receptor ligand LM11A-31-BHS dosed twice daily for 26 weeks. Successful completion of this trial will provide the safety, endpoint and statistical basis for the design and execution of a phase 2b/3 efficacy trial. It will also bring to the AD field a much-needed new set of target mechanisms and will help pioneer the strategy of the concomitant targeting of multiple fundamental AD-related pathological processes. During the 26 weeks study period the eligible patients will be invited to 5 visits. Safety monitoring will include the full extent of phase 2 clinical, electrophysiological and laboratory testing.
Interventions
DRUG400mg LM11A-31-BHS
1 Oral Capsules (200mg of LM11A-31-BHS and 200mg of placebo) twice daily (morning & evening) for 26 weeks
DRUG800mg LM11A-31-BHS
2 Oral Capsules (200mg of LM11A-31-BHS) twice daily (morning & evening) for 26 weeks
DRUGPlacebos
2 Oral Capsules (200mg of Placebo) twice daily (morning & evening) for 26 weeks
Sponsors
National Institute on Aging (NIA)
PharmatrophiX Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women (non-childbearing potential) with a diagnosis of Alzheimer's disease according to McKhann (2011) criteria 2. Age 50-85 years (50-80 in Czech Republic) 3. MRI or CT assessment within six months before baseline, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see
Exclusion criteria
, number 3) 4. CSF AD specific biomarker profile; positive, defined as CSF Aβ42 \< 550 ng l-1 or an Aβ 40/42 ratio \< 0.89 5. Mild to moderate stage of Alzheimer's disease according to MMSE ≥ 18 and ≤ 26 6. Absence of major depressive disease according to GDS of \< 5 7. Modified Hachinski Ischemic Scale ≤ 4 8. Formal education for eight or more years 9. Previous decline in cognition for more than six months as documented in patient medical records 10. A caregiver available and living in the same household or interacting with the patient a sufficient time each week (in Czech Republic: providing personal care for the patient during at least 10 hours per week ) and available if necessary to assure administration of drug 11. Patients living at home or nursing home setting without continuous nursing care 12. General health status acceptable for a participation in a 6-month clinical trial 13. Ability to swallow capsules 14. Stable pharmacological treatment of any other chronic condition for at least one month prior to screening 15. Stable treatment with one of the acetylcholinesterase inhibitors donepezil (Aricept ®), galantamine (Razadyne®), or rivastigmine (Exelon) or the partial NMDA receptor antagonist with memantine (Namenda®) at least 3-months before baseline Visit or Combination of both treatments mentioned above 16. No regular intake of prohibited medications as noted in Section 11.8 of the protocol 17. Signed informed consent by the patient, examined and verified to be mentally capable by an independent physician, prior to the initiation of any study specific procedure. Signed consent of the caregiver (see inclusion criteria 10).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of AEs/SAEs within the 26-week study period | 26 weeks | number of subjects with AEs/SAEs, changes in vital signs and laboratory examinations |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Statistically relevant changes in CSF-Biomarkers between baseline and final visit | 26 weeks | CSF-Biomarkers (tau, ptau, Aβ40, Aβ42, AchE activity) |
| Statistically relevant changes in working memory ability between baseline and final visit assessed with the Controlled Oral Word Association Test (COWAT) | 26 weeks | Controlled Oral Word Association Test (COWAT) |
| Statistically relevant changes in word fluency between baseline and final visit assessed with the Category Fluency Test (CFT) | 26 weeks | Category Fluency Test (CFT) |
| Statistically relevant changes in processing speed between baseline and final visit assessed with the Coding Test (Subtest of the Wechsler Adult Intelligence Scale) | 26 weeks | Coding Test (Subtest of the Wechsler Adult Intelligence Scale) |
| Statistically relevant changes in executive functions between baseline and final visit assessed with the Digit Span test (Subtest of the Wechsler Adult Intelligence Scale) | 26 weeks | Digit Span test (Subtest of the Wechsler Adult Intelligence Scale) |
Countries
Austria, Czechia, Germany, Spain, Sweden
Outcome results
None listed