MAD Study of NX210c (CHDR2235)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Elderly
• Intervention / Treatment: Drug: NX210c; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Daniel Dumas, MD; Phone Number: +31 71 5246 400; Email: clintrials@chdr.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333 CL
      • Recruiting
      • Centre for Human Drug Research
      • Contact: Philip Kremer, MD, PharmD, PhD; Phone Number: +31 71 5246 400; Email: clintrials@chdr.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Axoltis Pharma
• Collaborators: Centre for Human Drug Research, Netherlands
• Investigators: Principal Investigator: Philip Kremer, MD, PharmD, PhD, Centre for Human Drug Research

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: AXO-CLI-210c-02; 2022-002868-76 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymized subject data to be shared based on reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No