Safety, Tolerability, and Pharmacokinetics Study of NDX-1017

LeonaBio88 enrolled

Overview

This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of NDX-1017 in healthy young and elderly subjects, and elderly subjects with amnestic mild cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate).

NDX-1017 is being developed for the treatment of Alzheimer's disease (AD). This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of NDX-1017 in healthy young and elderly subjects, and elderly subjects with mild AD. The study contains the following two parts: Part A: A single-ascending dose (SAD) study conducted in an inpatient setting for 3 days in healthy young male and healthy elderly male and female volunteers evaluated in up to 7 dose cohorts to identify the maximum tolerated dose (MTD) within the single dose range studied. Up to 56 subjects (aged 18 to 45 years for young and 60 to 85 years for elderly) may be enrolled in Part A. Part B: A multiple ascending dose (MAD) study conducted in an inpatient setting for 10 days in male or female healthy elderly volunteers (aged 60 to 85 years) or subjects with amnestic mild cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate) (aged 40 to 85 years) in up to 6 dose cohorts that were proven tolerable in the SAD part of the study to identify the MTD within the multiple dose range studied. Up to 44 subjects (aged 40 to 85 years) may be enrolled in Part B. Subjects will be screened for eligibility within 28 days (or 90 days for amnestic MCI, Alzheimer's Disease, or mixed dementia with Alzheimer's and vascular components) prior to enrollment. Those eligible will be admitted to an inpatient facility for investigational product administration, safety monitoring, and collection of blood or urine for pharmacokinetic evaluations.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Alzheimer Disease

Interventions

NDX-1017DRUG

Solution of NDX-1017 for subcutaneous injection

PlaceboDRUG

Placebo solution for subcutaneous injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

INCLUSION CRITERIA: * Generally in good health * Body mass index (BMI) of ≥ 18.0 and ≤ 30.0 kg/m2 at Screening, with minimum weight of 60 kg. (No BMI upper limit for mild AD and amnestic MCI subjects) * Male subjects and their partners must be willing to comply with the contraceptive requirements of the study. Only female subjects of non-childbearing potential are eligible for participation. * \[Young subjects\] Male subjects must be aged 18 to 45 years (inclusive) at the time of Screening. * \[Healthy elder subjects only\] Male and female subjects must be aged 60 to 85 years at the time of screening * \[Amnestic MCI and Alzheimer's Subjects\] 9. Patients with Alzheimer's disease, with confirmed diagnosis of amnestic mild cognitive impairment, Alzheimer's disease (mild, mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate). 1. Either newly diagnosed treatment naïve patients, OR, 2. Patients who are currently on standard Alzheimer's Disease treatment may be considered for participation if they are not tolerating treatment and/or they are willing and clinically able to tolerate a discontinuation, 14 days for dose titration + 5x half-lives for washout, or 4 weeks (whichever is longer) prior to randomization. For these patients, the screening window will be allowed for up to 90 days prior to randomization to evaluate discontinuation of symptomatic treatment for Alzheimer's disease. EXCLUSION CRITERIA: * Any medical condition that requires chronic medication use. * History of drug and/or alcohol abuse within 12 months prior to Screening. * History of having taken another investigational drug within 30 days prior to Admission (Day -1). * Donation of blood or plasma within 30 days prior to dosing. * Major surgery within 90 days prior to Admission (Day -1) or anticipated surgery during the study. * Smokers * \[Healthy elderly subjects\] Reported changes in cognition and reported history of declines in everyday life in the last year.

Locations (1)

Biotrial Inc.

Newark, New Jersey, United States

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].

Safety and tolerability of single or multiple ascending doses of NDX-1017 as measured by vital signs and clinical laboratory measurements.

Time frame: Up to 20 days

Secondary Outcomes

Maximum observed plasma concentration (Cmax).

Cmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.