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Mild to Moderate Alzheimer's DiseasePhase 1/2NCT03069014

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

A Phase 1/2 study testing 400mg LM11A-31-BHS and 800mg LM11A-31-BHS in people with Mild to Moderate Alzheimer's Disease, run by PharmatrophiX Inc. at 21 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Mild to Moderate Alzheimer's Disease
What is being tested?
400mg LM11A-31-BHS and 800mg LM11A-31-BHS
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
242 participants
Where
21 sitesin 5 countries
Study dates
15 Feb 2017to 8 Jun 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • 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)
  • 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
Show all 17Show fewer
  • 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
  • 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).

Who cannot join

  • Failure to perform screening or baseline examinations
  • Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period
  • Clinical, laboratory or neuro-imaging findings consistent with:
  • Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down's syndrome, etc.)
  • Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.)
  • Cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions > one quarter of the total white matter)
Show all 34Show fewer
  • Other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, etc.)
  • Seizure disorder
  • Other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.)
  • A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder
  • Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as:
  • chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, Gamma GT, alkaline phosphatase > 2.5 ULN)
  • Respiratory insufficiency
  • Renal insufficiency (serum creatinine > 2mg/dl) or creatinine clearance ≤ 30 mL/min according to Cockcroft-Gault formula). In case of creatinine clearance ≤ 30mL/min, an alternative verification of the renal function must be completed using Cystatin C analysis. In case of normal level of Cystatin C, the patient can be included
  • Heart disease (myocardial infarction, unstable angina, heart failure, Cardiomyopathy within six months before screening)
  • Bradycardia (heart beat < 50/min.) or tachycardia (heart beat > 95/min.)
  • Hypertension (> 180/95 / Czech Republic >160/95) or hypotension (< 90/60) requiring treatment with more than three drugs
  • AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males > 450 and females > 470 msec.)
  • Uncontrolled diabetes defined by HbA1c > 8.5
  • Malignancies within the last five years except skin malignancies (other than melanoma) or indolent prostate cancer
  • Metastases
  • Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.)
  • Women who are fertile and of childbearing potential
  • Chronic daily drug intake of ≥ 14 days or expected for ≥ 14 days:
  • benzodiazepines (except lorazepam ≤ 1mg for sleeping disorders only), neuroleptics or major sedatives
  • Antiepileptics
  • Centrally active anti-hypertensive drugs (clonidine, l-methyl DOPA, guanidine, guanfacine, etc.)
  • Opioid containing analgesics
  • Nootropic drugs with exception of Ginko Biloba
  • Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine / in Czech Republic: 20 g alcohol per day for females (500 ml of beer or 250 ml of wine) and 30g alcohol per day for males (approximately 750 ml of beer or 375 ml of wine)) per day indicated by elevated MCV significantly above normal value at screening
  • Suspected or known allergy to any components of the study treatments
  • Enrollment in another investigational study or intake of investigational drug within the previous three months
  • Any condition, which, in the opinion of the investigator, makes the patient unsuitable for inclusion
  • If patient is in any way dependent on the sponsor or the principal investigator or if the patient is accommodated in an establishment on judicial or administrative order

Trial locations and contacts

21 sites in 5 countries.

21 sites in 5 countries

Germany9 sites

  • Sächsisches Krankenhaus Arnsdorf

    Arnsdorf, Saxony, 01477

  • Zentrum für klinische Forschung

    Bad Homburg, Hesse, 61348

  • Charité Universitätsmedizin Berlin

    Berlin, 13125

  • Pharmakologisches Studienzentrum Chemnitz GmbH

    Chemnitz, Saxony

  • Universitätsklinik Magdeburg, Klinik für Neurologie

    Magdeburg, Sachsen Anthal, 39120

  • Neurologie Sendlinger Strasse Studien- und Gedächtniszentrum München

    München, 80331

  • LMU München Klinik für Psychiatrie und Psychotherapie

    München, 80336

  • Nordwestkrankenhaus Sanderbusch

    Sande, Friesland, 26452

  • Studienzentrum Nordwest

    Westerstede, Lower Saxony, 26655

Other trials in Germany

Spain5 sites

  • Fundació ACE

    Barcelona, Catalonia, 08028

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

    Barcelona, Catalonia, 08036

  • Hospital Clínic de Barcelona

    Barcelona, Catalonia, 08036

  • Hospital la Paz

    Madrid, 28046

  • Hospital Virgen del Rocío

    Seville, 41013

Other trials in Spain

Czechia4 sites

  • Neurology Clinic of Martin Urbanek

    Brno, South Moravian, 60200

  • NEUROHK s.r.o

    Choceň, Pardubice Region, 56501

  • Charles University

    Prague, Prague, 16000

  • Vestra clinics s.r.o

    Rychnov nad Kněžnou, Kralovehadrecky Kraj, 51601

Other trials in Czechia

Austria2 sites

  • University Hospital Graz

    Graz, Styria, 8034

  • Landeskrankenhaus Hall

    Hall in Tirol, Tyrol, 6060

Other trials in Austria

Sweden1 site

  • Karolinska University

    Stockholm, Stockholms Iän, 14186

Other trials in Sweden

About this study

Official title: A 6-months Prospective, Multi-center, Double-blind, Placebo-controlled, Randomized, Adaptive-trial-design Study to Evaluate Safety, Tolerability and Exploratory Endpoints of Either Placebo or Two Different Oral Doses of LM11A-31-BHS in Patients With Mild to Moderate Probable Alzheimer's Disease

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

Read the 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.

Being tested
400mg LM11A-31-BHS, 800mg LM11A-31-BHS, Placebos

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 400mg LM11A-31-BHSDrug

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

  • 800mg LM11A-31-BHSDrug

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

  • PlacebosDrug

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

Study groups in NCT03069014
Study groupRoleWhat they receive
400mg LM11A-31-BHSActive comparator400mg LM11A-31-BHS and 400mg Placebo per day
Receives: Drug: 400mg LM11A-31-BHS; Drug: Placebos
800mg LM11A-31-BHSActive comparator800mg LM11A-31-BHS
Receives: Drug: 800mg LM11A-31-BHS
PlacebosPlacebo comparator800mg (microcrystalline cellulose with 0.5 - 1% magnesium stearate) per day
Receives: Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: 26 weeks

Secondary outcomes (5)

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

    CSF-Biomarkers (tau, ptau, Aβ40, Aβ42, AchE activity)

    Measured: 26 weeks

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

    Controlled Oral Word Association Test (COWAT)

    Measured: 26 weeks

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

    Category Fluency Test (CFT)

    Measured: 26 weeks

  4. Statistically relevant changes in processing speed between baseline and final visit assessed with the Coding Test (Subtest of the Wechsler Adult Intelligence Scale)

    Coding Test (Subtest of the Wechsler Adult Intelligence Scale)

    Measured: 26 weeks

  5. Statistically relevant changes in executive functions between baseline and final visit assessed with the Digit Span test (Subtest of the Wechsler Adult Intelligence Scale)

    Digit Span test (Subtest of the Wechsler Adult Intelligence Scale)

    Measured: 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2017
  2. Study start15 Feb 2017
  3. Primary completion8 Jun 2020
  4. Study completion8 Jun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
242 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03069014
Sponsor's protocol ID
NSC15001
Other IDs
2015-005263-16, 1R01AG051596-01A1, 2015
Status last verified
Sep 2020
First submitted
3 Feb 2017
Last updated
4 Sep 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38760589

  • 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.

    PubMed 38029807

  • 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.

    PubMed 34334250

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 400mg LM11A-31-BHS and 800mg LM11A-31-BHS in people with Mild to Moderate Alzheimer's Disease, run by PharmatrophiX Inc. at 21 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Germany, Spain, Czechia, Austria, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of AEs/SAEs within the 26-week study period (time frame: 26 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03069014, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2020.

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