MAD Study of NX210c

Study Overview
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Brief Summary
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This study will investigate the safety and tolerability of multiple intravenous infusions of NX210c with two ascending doses as well as NX210c pharmacokinetics (PK), and pharmacodynamics (PD) effects, firstly in healthy elderly subjects, and the recommended dose to be used for Alzheimer's disease patients, in a second step.

Detailed Description
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The prevalence of neurocognitive disorders (NCD), including neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) is increasing. NDDs are most common and prevalent in elderly people worldwide and cause progressive neuronal dysfunction, toxicities, and death. These diseases lead to an irreversible weakening of all brain functions, including cognitive impairment. There is not one single cause of cognitive impairment but rather several factors that can contribute to trigger or accelerate cognitive decline. Preclinical in vitro and in vivo data have shown that NX210c exhibits important properties, which may be suitable for the treatment of neurological disorders in humans. (i.e., neuroprotection, neuro-regeneration, synaptic transmission, positive effects on cognition, anti-neuroinflammatory action). The First In Human Single Ascending Dose study has been completed. In that study, NX210 was administered and well tolerated. The current project is a multiple ascending dose (MAD) study and designed to investigate the safety, tolerability, PK and pharmacodynamics (PD) effects of multiple intravenous infusions of NX210c in two dose levels in healthy elderly subjects. An additional cohort enrolling patient with Alzheimer disease (AD) to further evaluate NX210c is planned for this study but design is still in development.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multiple Ascending Dose (MAD) Study in Healthy Elderly Volunteers and Alzheimer's Disease (AD) Patients to Investigate the Safety and Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) Effects of Multiple Intravenous Infusions of NX210c

Conditions
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Healthy Elderly

Intervention / Treatment
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* Drug: NX210c
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male or female participants, as determined by the Investigator, based upon a medical evaluation including medical history, physical examination, neurological examination, MMSE, MRI, lab tests and ECG. Aged ≥ 55 years, inclusive at screening, and with a maximum weight of 110 kg. Body mass index (BMI) between 18 and 32 kg/m2, inclusive at screening. Exclusion Criteria: Evidence of any history, or any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator History of any known neurologic disease, cognitive impairment, or diagnosed decline in cognitive function abnormal related to the age, or history of seizure, (significant) head trauma, loss of consciousness, or significant neuroimaging findings, including but not limited to any previously known or discovered abnormalities on screening brain MRI that evoke neurological diagnosis indicative of clinically significant abnormality

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A double-blind, randomized, placebo-controlled, multiple ascending dose study to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic effects of multiple intravenous infusions of NX210c. Two doses will be investigated. Subjects will participate for approx. 124 days; up to 84 days for screening, 26 days of treatment and 14 days Follow-up. As part of the screening process subjects will undergo MRI and Mini-Mental State Examination to establish normal cognitive capacity and exclude any major neurological condition. Blood for PK will be drawn as well as for biomarkers testing. A CNS battery of pharmacodynamic measures including EEG and MRI will be performed, as well as Lumbar punctures for cerebrospinal fluid drug concentration determination and biomarker testing. The study will be overseen by a safety review committee, sentinel dosing will be applied for each cohort. The rest of the cohort will be dosed if administration of NX210c is safe and well tolerated.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1_active<br>Dose 1 NX210c | Drug: NX210c<br>* 3 times a week, for 28 days<br>|
| Experimental: Cohort 1_placebo<br>Placebo | Drug: Placebo<br>* 3 times a week, for 28 days<br>|
| Experimental: Cohort 2_active<br>Dose 2 (TBC) NX210c. | Drug: NX210c<br>* 3 times a week, for 28 days<br>|
| Experimental: Cohort 2_placebo<br>Placebo | Drug: Placebo<br>* 3 times a week, for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity and incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs) | Severity and incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs) | Up to 16 days after last dose |