Study of LM11A-31-BHS in Mild-moderate AD Patients

NCT03069014 | Completed Phase 1 DMC

• 3 other identifiers: NSC150012015-005263-161R01AG051596-01A1
• Study Type: interventional
• Target: 242
• Locations: 5 countries
• Sites: 21

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

Conditions

Mild to Moderate Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Number of AEs/SAEs within the 26-week study period

  number of subjects with AEs/SAEs, changes in vital signs and laboratory examinations

  26 weeks

Secondary Outcomes (5)

• Statistically relevant changes in CSF-Biomarkers between baseline and final visit

  26 weeks

• Statistically relevant changes in working memory ability between baseline and final visit assessed with the Controlled Oral Word Association Test (COWAT)

  26 weeks

• Statistically relevant changes in word fluency between baseline and final visit assessed with the Category Fluency Test (CFT)

  26 weeks

• 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

• 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

Study Arms (3)

400mg LM11A-31-BHS

ACTIVE COMPARATOR

400mg LM11A-31-BHS and 400mg Placebo per day

Drug: 400mg LM11A-31-BHS; Drug: Placebos

800mg LM11A-31-BHS

ACTIVE COMPARATOR

800mg LM11A-31-BHS

Drug: 800mg LM11A-31-BHS

Placebos

PLACEBO COMPARATOR

800mg (microcrystalline cellulose with 0.5 - 1% magnesium stearate) per day

Drug: Placebos

Interventions

400mg LM11A-31-BHS DRUG

1 Oral Capsules (200mg of LM11A-31-BHS and 200mg of placebo) twice daily (morning \& evening) for 26 weeks

400mg LM11A-31-BHS

800mg LM11A-31-BHS DRUG

2 Oral Capsules (200mg of LM11A-31-BHS) twice daily (morning \& evening) for 26 weeks

800mg LM11A-31-BHS

Placebos DRUG

2 Oral Capsules (200mg of Placebo) twice daily (morning \& evening) for 26 weeks

400mg LM11A-31-BHS; Placebos

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women (non-childbearing potential) with a diagnosis of Alzheimer's disease according to McKhann (2011) criteria
• Age 50-85 years (50-80 in Czech Republic)

You may not qualify if:

• CSF AD specific biomarker profile; positive, defined as CSF Aβ42 \< 550 ng l-1 or an Aβ 40/42 ratio \< 0.89
• Mild to moderate stage of Alzheimer's disease according to MMSE ≥ 18 and ≤ 26
• Absence of major depressive disease according to GDS of \< 5
• Modified Hachinski Ischemic Scale ≤ 4
• Formal education for eight or more years
• Previous decline in cognition for more than six months as documented in patient medical records
• 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
• Patients living at home or nursing home setting without continuous nursing care
• General health status acceptable for a participation in a 6-month clinical trial
• Ability to swallow capsules
• Stable pharmacological treatment of any other chronic condition for at least one month prior to screening
• 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
• No regular intake of prohibited medications as noted in Section 11.8 of the protocol
• Failure to perform screening or baseline examinations
• Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period

Sponsors & Collaborators

• PharmatrophiX Inc.: lead
• National Institute on Aging (NIA): collaborator

Study Sites (21)

University Hospital Graz

Graz, Styria, 8034, Austria

Location

Landeskrankenhaus Hall

Hall in Tirol, Tyrol, 6060, Austria

Location

Vestra clinics s.r.o

Rychnov nad Kněžnou, Kralovehadrecky Kraj, 51601, Czechia

Location

NEUROHK s.r.o

Choceň, Pardubický kraj, 56501, Czechia

Location

Charles University

Prague, Prague, 16000, Czechia

Location

Neurology Clinic of Martin Urbanek

Brno, South Moravian, 60200, Czechia

Location

Nordwestkrankenhaus Sanderbusch

Sande, Friesland, 26452, Germany

Location

Zentrum für klinische Forschung

Bad Homburg, Hesse, 61348, Germany

Location

Studienzentrum Nordwest

Westerstede, Lower Saxony, 26655, Germany

Location

Universitätsklinik Magdeburg, Klinik für Neurologie

Magdeburg, Sachsen Anthal, 39120, Germany

Location

Sächsisches Krankenhaus Arnsdorf

Arnsdorf, Saxony, 01477, Germany

Location

Pharmakologisches Studienzentrum Chemnitz GmbH

Chemnitz, Saxony, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 13125, Germany

Location

Neurologie Sendlinger Strasse Studien- und Gedächtniszentrum München

München, 80331, Germany

Location

LMU München Klinik für Psychiatrie und Psychotherapie

München, 80336, Germany

Location

Fundació ACE

Barcelona, Catalonia, 08028, Spain

Location

Fundación de Gestión Sanitaria del Hospital de la Santa Creu I Sant Pau, C

Barcelona, Catalonia, 08036, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Hospital la Paz

Madrid, 28046, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Karolinska University

Stockholm, Stockholms Iän, 14186, Sweden

Location

Related Publications (3)

• Shanks HRC, Chen K, Reiman EM, Blennow K, Cummings JL, Massa SM, Longo FM, Borjesson-Hanson A, Windisch M, Schmitz TW. p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial. Nat Med. 2024 Jun;30(6):1761-1770. doi: 10.1038/s41591-024-02977-w. Epub 2024 May 17.

  PMID: 38760589 DERIVED

• Liu G, He M, Wu C, Lv P, Sun H, Wang H, Xin X, Liao H. Axonal injury mediated by neuronal p75NTR/TRAF6/JNK pathway contributes to cognitive impairment after repetitive mTBI. Exp Neurol. 2024 Feb;372:114618. doi: 10.1016/j.expneurol.2023.114618. Epub 2023 Nov 27.

  PMID: 38029807 DERIVED

• Malik SC, Sozmen EG, Baeza-Raja B, Le Moan N, Akassoglou K, Schachtrup C. In vivo functions of p75NTR: challenges and opportunities for an emerging therapeutic target. Trends Pharmacol Sci. 2021 Sep;42(9):772-788. doi: 10.1016/j.tips.2021.06.006. Epub 2021 Jul 29.

  PMID: 34334250 DERIVED

Study Officials

• Manfred Windisch, PhD

  NeuroScios GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2017
• First Posted: March 3, 2017
• Study Start: February 15, 2017
• Primary Completion: June 8, 2020
• Study Completion: June 8, 2020
• Last Updated: September 4, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); AU (2); ES (5); CZ (4); DE (9)