A Study to Assess Safety and Tolerability and to Explore Efficacy of NSC001 in Mild to Moderate Alzheimer's Disease

NCT06995573 | Recruiting Phase 1 DMC

• 2 other identifiers: NSC240012024-518563-35-00
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 10

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of NSC001 on in patients with mild to moderate Alzheimer's disease and to evaluate the influence of the compound on cognitive function.

Conditions

Alzheimer Disease

Keywords

Mild to Moderate Alzheimer's Disease

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of NSC001

  Number of Adverse Events (AEs) between V1 (Baseline) -V5 (End of Treatment)

  Week 0 and week16

• Safety during the treatment period

  Number of Serious Adverse Events (SAEs) between V1 (Baseline) -V5 (End of Treatment)

  Week 0 and week16

Secondary Outcomes (4)

• Maximum concentration in plasma

  At week 0, 1, 2, 3, 4, 16 at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4 and 6 hours)

• Time at maximum concentration in plasma

  At week 0, 1, 2, 3, 4, 16 at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4 and 6 hours)

• Area under the curve

  At week 0, 1, 2, 3, 4, 16 at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4 and 6 hours)

• Half Life of NSC001 in plasma

  At week 0, 1, 2, 3, 4, 16 at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4 and 6 hours)

Other Outcomes (10)

• ADAS-cog as exploratory outcome on cognitive function and neuropsychiatric symptoms

  At week 0, 4, 16

• MMSE as exploratory outcome on cognitive function and neuropsychiatric symptoms

  At week 0, 1, 2, 3, 4, 16

• Concentration of NFL as exploratory outcome on blood-based AD-related biomarkers

  At week 0,4,16

Study Arms (3)

Arm 1

EXPERIMENTAL

40 mg QD of NSC001

Drug: NSC001

Arm 2

EXPERIMENTAL

40 mg QD of NSC001 + 20 mg of Trospium

Drug: NSC001

Arm 3

PLACEBO COMPARATOR

Placebo: with or without 20 mg of Trospium

Other: Placebo

Interventions

NSC001 DRUG

rigid, orthosteric acetylcholine analog, highly specific for M1 muscarinic receptor

Arm 1; Arm 2

Placebo OTHER

matching placebo to NSC001

Arm 3

Eligibility Criteria

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

You may qualify if:

• Participants and competent trial partner/caregiver are willing and able to give signed informed consent for participation in the trial including compliance with the requirements and restrictions according to local regulations for the trial Informed Consent Form (ICF). Signed informed consent by the patient (examined and verified to be mentally capable by an independent physician/ neurologist) prior to the initiation of any study specific procedure.
• Must have an informant or trial partner who, in the Investigator's judgment, has frequent and sufficient contact with the participant (at least 10 hours/week), who is considered reliable by the Investigator in providing support to the participant to ensure compliance with the trial intervention, including the proper and consistent intake of the study medication, who can accompany the participant to trial visits and help with protocol procedures, and who is also able and willing to provide input for completing the caregiver scales and sign the caregiver consent form.
• Male or female aged 50 to 85 years, inclusive at the time of consent.
• Female trial participants must be post-menopausal for at least 2 consecutive years or surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months prior to screening.
• Male trial participants with partners who are women of childbearing potential (WOCBP) must agree to use a reliable means of contraception (e.g., minimum condom + spermicide) during the trial and 6 months after discontinuing the trial intervention
• Participants who have a clinical diagnosis of AD, which falls into the stages of mild to moderate dementia (Stage 4 to 5) according to the utilized by the NIA-AA 2018 criteria at screening.
• Patients who show CSF biomarker data supporting the diagnosis of AD measured within the last 3 years or patients with a positive Amyloid Pet Scan within the last 3 years or have a test on p-tau217 in plasma indicating brain amyloid positivity will qualify for the study. Plasma pTau217 concentration of ≥ 2.0 pg/mL.
• Evidence of cognitive decline over the last year must be present based on informant observation, medical records, or objective neurocognitive testing.
• Magnetic resonance imaging (MRI) or computed tomography (CT) scan performed within 12 months before screening, with findings consistent with the clinical diagnosis of mild to moderate AD without any other clinically significant comorbid pathologies, especially cerebrovascular lesions. If an MRI or CT scan is unavailable within 12 months before screening, an MRI assessment should be completed, and the findings confirmed before the participant's treatment start (V1).
• Mini-Mental State Examination (MMSE) score of ≥18 and ≤26 at screening.
• Modified Hachinski Ischemic (mHIS) Scale ≤4 unless recent MRI study demonstrates no vascular causes for dementia.
• Use of AChEIs (e.g., donepezil, galantamine, or rivastigmine) is mandatory and treatment must be on a stable dose for at least 3 months prior to baseline
• Adequate vision, hearing, and motor function to comply with testing.
• Ability to swallow size 2 capsules.
• In the opinion of the Investigator is in reasonably good health for 21-week trial participation.

You may not qualify if:

• Inability to comply with visit schedule or other protocol requirements and failure to perform screening and baseline first treatment visit (V1) assessments.
• Planned start of NMDA receptor antagonist memantine during the trial period (i.e., the next 13 weeks) or use of memantine within the past 4 weeks before screening, unless at a stable dose for at least 8 weeks prior to screening.
• Prior use of anti-beta-amyloid immunotherapy (e.g., Aducanumab, Leqanemab, Donanemab) or administration of anti-amyloid vaccine.
• Enrollment in another investigational clinical trial and, respectively, administration of investigational drug within the previous 3 months small molecules. Previous participation in investigational clinical trials with monoclonal antibodies against amyloid or other anti-beta amyloid immunotherapy and other biologicals.
• Current use of anticholinergics, including trospium within the past 2 weeks before screening.
• Use of the following medications:
• Long-acting benzodiazepines (e.g., valium), except for sedation prior to screening MRI scans for those participants requiring sedation and should not be administered within 24 hours prior to cognitive testing.
• Short/medium-acting benzodiazepines (e.g., alprazolam, lorazepam, oxazepam, temazepam) except if used chronically for sleep and on a stable dose for ≥4 weeks prior to screening and throughout the trial. May not be taken within 12 hours prior to cognitive testing.
• Sedating antihistamines if taken within 12 hours prior to cognitive testing (Non-sedating antihistamines \[e.g., fexofenadine, cetirizine\] are allowed).
• Anticonvulsants that have significant effects on cognition per the Investigator's opinion and/or anticonvulsants used for treatment of seizures. Anticonvulsants with limited cognitive effects, such as lamotrigine, pregabalin, levetiracetam for the treatment of pain, and other non-epilepsy indications are allowed if, in the opinion of the Investigator, they are not producing sedation or contributing to cognitive impairment. The participant must have been on a stable dose for ≥4 weeks prior to screening and throughout the trial.
• Antipsychotics used regularly, except for low doses of atypical antipsychotics (e.g., risperidone, aripiprazole, or quetiapine) if used on an as-needed basis or if used at a stable dose for ≥4 weeks prior to screening and throughout the duration of the trial. The definition of "low doses" should be judged by the Investigator, and the Medical Monitor can be consulted if needed.
• Prior use of levodopa or anti-Parkinsonian medications including dopaminergic agents, amantadine, selegiline, benztropine, and monoamine oxidase (MAO) inhibitors prescribed for the treatment of Parkinsonism or Parkinson's disease.
• Use of prescription narcotic medications within 4 weeks prior to screening. After randomization, short-term use of prescription narcotics is allowed for specific situations (e.g., after surgical procedures) and if administered at least 24 hours prior to cognitive testing.
• Use of drugs with known QT-prolonging effects36, unless used at a stable dose for ≥12 weeks prior to screening and throughout the duration of the trial, and with demonstrated stable QT interval on treatment.
• Use of any drug of abuse, including but not limited to, amphetamine, cannabis, cocaine, opiate, propoxyphene, methadone, methaqualone, phencyclidine, or barbiturates.

Sponsors & Collaborators

• NSC-Therapeutics: lead
• NeuroScios GmbH: collaborator

Study Sites (10)

Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft GmbH

Salzburg, State of Salzburg, 5020, Austria

RECRUITING

University Hospital Graz

Graz, Styria, 8036, Austria

RECRUITING

Medical University Innsbruck

Innsbruck, 6020, Austria

RECRUITING

Medical University Vienna

Vienna, 1090, Austria

RECRUITING

Clinic Altenburger Land GmbH

Altenburg, 04600, Germany

NOT YET RECRUITING

Zentrum fuer klinische Forschung Dr. I. Schoell GmbH

Bad Homburg, 61348, Germany

RECRUITING

University Clinic Köln

Cologne, 50937, Germany

RECRUITING

Universitaetsmedizin Goettingen

Göttingen, 37075, Germany

RECRUITING

Dynamikos GmbH Institut fuer Studien zur Psychischen Gesundheit

Mannheim, 68165, Germany

RECRUITING

SANOS Clinic

Ratingen, 40882, Germany

RECRUITING

Related Publications (2)

• Fisher A. Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer's disease. J Neurochem. 2012 Jan;120 Suppl 1:22-33. doi: 10.1111/j.1471-4159.2011.07507.x. Epub 2011 Nov 28.

  PMID: 22122190 BACKGROUND

• Fisher A. Cholinergic treatments with emphasis on m1 muscarinic agonists as potential disease-modifying agents for Alzheimer's disease. Neurotherapeutics. 2008 Jul;5(3):433-42. doi: 10.1016/j.nurt.2008.05.002.

  PMID: 18625455 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Manfred Windisch, PhD

  NSC-Therapeutics GmbH

  STUDY CHAIR

Central Study Contacts

Barbara Fridrich, DI

CONTACT

004366488869909; bfridrichl@neuroscios.com

Klara Fuereder, MSC

CONTACT

00436645472844; kfuereder@neuroscios.com

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: April 2, 2025
• First Posted: May 29, 2025
• Study Start: August 25, 2025
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); DE (6)